Brain Sciences

12 pages, 622 KiB

Open AccessArticle

Psychophysiological Effects of a Single Dose vs. Partial Dose of Caffeine Gum Supplementation on the Cognitive Performance of Healthy University Students: A Placebo Controlled Study

by Nicolas Saavedra Velasquez, Giovanni Francino Barrera, Victor Cuadrado Peñafiel and Ricardo de la Vega Marcos

Brain Sci. 2025, 15(5), 536; https://doi.org/10.3390/brainsci15050536 - 21 May 2025

Viewed by 813

Abstract

Background: Caffeine has become the psychostimulant with the highest use worldwide by different segments of the population. This is mainly due to the wide variety of benefits it offers in different contexts of use. It is available in various forms, with caffeine chewing [...] Read more.

Background: Caffeine has become the psychostimulant with the highest use worldwide by different segments of the population. This is mainly due to the wide variety of benefits it offers in different contexts of use. It is available in various forms, with caffeine chewing gum recently generating great interest due to its characteristics and absorption time. Methods: A placebo-controlled study was conducted in which 20 healthy university students were exposed to three different conditions (single dose, partial dose, and placebo). The intervention consisted of a dual task in which heart rate, perceived exertion, and reaction time were monitored using the Stroop test and choice reaction time test while participants performed two blocks of cycloergometer exercise. Results: A t-test comparison between blocks showed differences in the Stroop test under all conditions, with the single dose having the best performance (Gr.A p < 0.001; Gr.B p < 0.029; Gr.C p < 0.009). The single dose group also showed favorable results for the HR/RPE ratio (p < 0.044) and an increase in the rate of perceived exertion (p < 0.006). No changes in reaction time were observed under any condition of the choice reaction time test. Conclusions: These results suggest that caffeine supplementation has positive effects on variables related to psychophysiological performance during a dual task. A single dose showed the best results in this study; however, longer intervention designs could be considered in the future to see the effect of partial doses of caffeine over time. Full article

(This article belongs to the Special Issue Mind in Motion: Exploring Neuropsychophysiological Aspects of Sports Performance, Health and Physical Activity)

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18 pages, 868 KiB

Open AccessReview

The Effects of Deep Brain Stimulation on Balance in Parkinson’s Disease as Measured Using Posturography—A Narrative Review

by Bradley Lonergan, Barry M. Seemungal, Matteo Ciocca and Yen F. Tai

Brain Sci. 2025, 15(5), 535; https://doi.org/10.3390/brainsci15050535 - 21 May 2025

Viewed by 780

Abstract

Background: Postural imbalance with falls affects 80% of patients with Parkinson’s disease (PD) at 10 years. Standard PD therapies (e.g., levodopa and/or deep brain stimulation—DBS) are poor at improving postural imbalance. Additionally, the mechanistic complexity of interpreting postural control is a major barrier [...] Read more.

Background: Postural imbalance with falls affects 80% of patients with Parkinson’s disease (PD) at 10 years. Standard PD therapies (e.g., levodopa and/or deep brain stimulation—DBS) are poor at improving postural imbalance. Additionally, the mechanistic complexity of interpreting postural control is a major barrier to improving our understanding of treatment effects. In this paper, we review the effects of DBS on balance as measured using posturography. We also critically appraise the quantitative measures and analyses used in these studies. Methods: A literature search was performed independently by 2 researchers using the PUBMED database. Thirty-eight studies are included in this review, with DBS at the subthalamic nucleus (STN-) (n = 25), globus pallidus internus (GPi-) (n = 6), ventral intermediate nucleus (VIM)/thalamus (n = 2), and pedunculopontine nucleus (PPN) (n = 5). Results: STN- and GPi-DBS reduce static sway in PD and mitigate the increased sway from levodopa. STN-DBS impairs automatic responses to perturbations, whilst GPi-DBS has a more neutral effect. STN-DBS may promote protective strategies following external perturbations but does not improve adaptation. The evidence regarding the effects on gait initiation is less clear. Insufficient evidence exists to make conclusions regarding VIM- and PPN-DBS. Conclusions: STN- and GPi-DBS have differing effects on posturography, which suggests site-specific and possibly non-dopaminergic mechanisms. Posturography tests should be utilised to answer specific questions regarding the mechanisms of and effects on postural control following DBS. We recommend standardising posturography measures and test conditions by expert consensus and greater long-term data collection, utilising ongoing DBS registries. Full article

(This article belongs to the Special Issue Advances in Deep Brain Stimulation for Parkinson's Disease and Other Movement Disorders)

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27 pages, 6846 KiB

Open AccessArticle

Chronic Stress Modulates Microglial Activation Dynamics, Shaping Priming Responses to Subsequent Stress

by Junyu Chen, Jiacheng Huang, Taolei Han and Nobuhiko Kojima

Brain Sci. 2025, 15(5), 534; https://doi.org/10.3390/brainsci15050534 - 21 May 2025

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Abstract

(1) Background: The high recurrence rate and individual differences in stress susceptibility contribute to the diverse symptoms of depression, making full recovery and relapse prevention challenging. Emerging evidence suggests that fluctuations in microglial activity are closely linked to depression progression under chronic stress [...] Read more.

(1) Background: The high recurrence rate and individual differences in stress susceptibility contribute to the diverse symptoms of depression, making full recovery and relapse prevention challenging. Emerging evidence suggests that fluctuations in microglial activity are closely linked to depression progression under chronic stress exposure. Changes in the brain microenvironment can elicit microglial priming, enhancing their sensitivity to external stimuli. However, few studies have longitudinally examined how microglial characteristics evolve throughout depression progression. (2) Methods: In this study, we investigated microglial morphological changes and their responses to acute stress at different stages of depression using the chronic unpredictable mild stress (CUMS) paradigm in mice. (3) Results: Our findings reveal that in the dentate gyrus, microglial activation indices, including cell number and morphology, exhibit distinct dynamic patterns depending on CUMS exposure duration. Notably, after 2 and 4 weeks of CUMS exposure followed by acute stress re-exposure, microglia display opposing response patterns. In contrast, after 6 weeks of CUMS exposure, primed microglia exhibit dysfunction, failing to respond to acute stress. Notably, depressive behaviors are not prominent after 2 weeks of CUMS exposure but become more pronounced after 4 and 6 weeks of exposure. Additionally, regardless of CUMS duration, body weight demonstrates an intrinsic capacity to normalize after stress cessation. (4) Conclusions: These findings suggest that microglial priming responses are state-dependent, either enhancing or suppressing secondary stimulus responses, or exceeding physiological limits, thereby preventing further activation. This study provides novel insights into the role of microglial priming in stress vulnerability and its contribution to depression progression. Full article

(This article belongs to the Special Issue Stress, Resilience and Susceptibility)

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25 pages, 2106 KiB

Open AccessPerspective

Digital Biomarkers and AI for Remote Monitoring of Fatigue Progression in Neurological Disorders: Bridging Mechanisms to Clinical Applications

by Thorsten Rudroff

Brain Sci. 2025, 15(5), 533; https://doi.org/10.3390/brainsci15050533 - 21 May 2025

Viewed by 752

Abstract

Digital biomarkers for fatigue monitoring in neurological disorders represent an innovative approach to bridge the gap between mechanistic understanding and clinical application. This perspective paper examines how smartphone-derived measures, analyzed through artificial intelligence methods, can transform fatigue assessment from subjective, episodic reporting to [...] Read more.

Digital biomarkers for fatigue monitoring in neurological disorders represent an innovative approach to bridge the gap between mechanistic understanding and clinical application. This perspective paper examines how smartphone-derived measures, analyzed through artificial intelligence methods, can transform fatigue assessment from subjective, episodic reporting to continuous, objective monitoring. The proposed framework for smartphone-based digital phenotyping captures passive data (movement patterns, device interactions, and sleep metrics) and active assessments (ecological momentary assessments, cognitive tests, and voice analysis). These digital biomarkers can be validated through a multimodal approach connecting them to neuroimaging markers, clinical assessments, performance measures, and patient-reported experiences. Building on the previous research on frontal–striatal metabolism in multiple sclerosis and Long-COVID-19 patients, digital biomarkers could enable early warning systems for fatigue episodes, objective treatment response monitoring, and personalized fatigue management strategies. Implementation considerations include privacy protection, equity concerns, and regulatory pathways. By integrating smartphone-derived digital biomarkers with AI analysis approaches, the future envisions fatigue in neurological disorders no longer as an invisible, subjective experience but rather as a quantifiable, treatable phenomenon with established neural correlates and effective interventions. This transformative approach has significant potential to enhance both clinical care and the research for millions affected by disabling fatigue symptoms. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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15 pages, 1384 KiB

Open AccessArticle

Real-World Use of COMT Inhibitors in the Management of Patients with Parkinson’s Disease in Spain Who Present Early Motor Fluctuations: Interim Results from the REONPARK Study

by Lydia López-Manzanares, Juan García Caldentey, Marina Mata Álvarez-Santullano, Dolores Vilas Rolán, Jaime Herreros-Rodríguez, Berta Solano Vila, María Cerdán Sánchez, Tania Delgado Ballestero, Rocío García-Ramos, Ana Rodríguez-Sanz, Jesús Olivares Romero, José Blanco Ameijeiras, Isabel Pijuan Jiménez and Iciar Tegel Ayuela

Brain Sci. 2025, 15(5), 532; https://doi.org/10.3390/brainsci15050532 - 21 May 2025

Viewed by 577

Abstract

Objective: We aimed to analyze the real-world use of COMT inhibitors associated with levodopa in patients with Parkinson’s disease (PD) who present early fluctuations and to explore whether early COMT inhibition optimizes treatment outcomes. Methods: REONPARK is an ongoing 2-year prospective observational study. [...] Read more.

Objective: We aimed to analyze the real-world use of COMT inhibitors associated with levodopa in patients with Parkinson’s disease (PD) who present early fluctuations and to explore whether early COMT inhibition optimizes treatment outcomes. Methods: REONPARK is an ongoing 2-year prospective observational study. We included patients diagnosed with PD who presented signs of end-of-dose motor fluctuations for <2 years and started COMT inhibitors according to clinical practice. Outcomes included the clinician and patient global impression of change (CGI-C, PGI-C), the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Parkinson’s Disease Questionnaire-8 (PDQ-8), Non-Motor Symptoms Scale (NMSS), 19-Symptom Wearing-off Questionnaire (WOQ-19), and safety. We present a pre-planned interim analysis (cut-off date 3 July 2023) of patients who completed the first 3 months of follow-up. Results: Seventy patients were analyzed (mean levodopa dose at inclusion 484.8 mg; duration of motor fluctuations 0.6 years). In all cases, COMT inhibition was initiated with opicapone, and 81% maintained a stable levodopa dose at 3 months. After 3 months of treatment with opicapone, 73.5% and 62.8% of patients improved on CGI-C and PGI-C, respectively. MDS-UPDRS scores improved significantly with a mean change from baseline of −3.3 ± 7.7 (p < 0.001) for Part III and −1.3 ± 1.7 (p < 0.001) for Part IV. The mean OFF time decreased from 3.7 ± 2.6 h at baseline to 2.2 ± 2.3 h, and 20.6% of patients no longer experienced OFF periods. Patients experiencing no impact of fluctuations increased from 10% to 45.6%. Conclusions: In PD patients with early fluctuations, three months of opicapone reduced the OFF time and improved functional outcomes, suggesting potential benefits in the early stages. Full article

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Graphical abstract

13 pages, 4016 KiB

Open AccessArticle

Effects of Matched and Mismatched Visual Flow and Gait Speeds on Human Electrocortical Spectral Power

by Yu-Po Cheng and Andrew D. Nordin

Brain Sci. 2025, 15(5), 531; https://doi.org/10.3390/brainsci15050531 - 21 May 2025

Viewed by 516

Abstract

Background/Objectives: Visuomotor integration relies on synchronized proprioceptive and visual feedback during visually guided locomotion. How the human brain processes unimodal or asynchronous multimodal inputs during locomotion is unclear. Methods: Using high-density mobile electroencephalography (EEG) and motion capture in a virtual reality [...] Read more.

Background/Objectives: Visuomotor integration relies on synchronized proprioceptive and visual feedback during visually guided locomotion. How the human brain processes unimodal or asynchronous multimodal inputs during locomotion is unclear. Methods: Using high-density mobile electroencephalography (EEG) and motion capture in a virtual reality environment, we investigated electrocortical responses during altered treadmill gait speeds (0.5 and 1.5 m/s) and visual flow speeds (0.5×, 1×, and 1.5× gait speed) among 13 healthy human subjects. Experimental conditions included passive viewing of a moving virtual environment, walking in a stationary virtual environment, and walking in a moving environment with synchronous and asynchronous visual flow. Results: At faster gait speed, we identified reduced premotor, sensorimotor, and visual electrocortical beta-band spectral power (13–30 Hz) and greater premotor cortex theta power (4–8 Hz). At faster visual flow speeds, we identified reduced sensorimotor electrocortical beta-band spectral power, reduced alpha (8–13 Hz) and beta power, and greater gamma-band power (30–50 Hz) from the visual cortex. During visual flow and gait speed mismatches, sensorimotor and parietal alpha- and beta-band electrocortical spectral power decreased at faster gait speed. During treadmill walking at 1.5 m/s, parietal electrocortical spectral power increased when visual flow exceeded gait speed. Conclusions: Electrical brain dynamics during human gait identified distinct neural circuits for integrating kinesthetic and visual information during visuomotor conflicts, gated by the parietal cortex. Full article

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

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14 pages, 1060 KiB

Open AccessProtocol

Longitudinal Effects of Transcranial Direct Current Stimulation on Daily Rejection-Related Emotions in Borderline Personality Disorder: An Ecological Momentary Assessment Study Protocol

by Chiara De Panfilis, Alessandro Lisco, Kevin B. Meehan, Maria Lidia Gerra, Emanuele Preti, Paolo Riva and Leonor Josefina Romero Lauro

Brain Sci. 2025, 15(5), 530; https://doi.org/10.3390/brainsci15050530 - 20 May 2025

Viewed by 435

Abstract

Background: Borderline Personality Disorder (BPD) is a debilitating mental health condition characterized by emotional dysregulation and interpersonal dysfunction, with perceived social rejection exacerbating these issues. Emerging evidence suggests that a single session of transcranial direct current stimulation (tDCS) over the right ventrolateral prefrontal [...] Read more.

Background: Borderline Personality Disorder (BPD) is a debilitating mental health condition characterized by emotional dysregulation and interpersonal dysfunction, with perceived social rejection exacerbating these issues. Emerging evidence suggests that a single session of transcranial direct current stimulation (tDCS) over the right ventrolateral prefrontal cortex (rVLPFC) may decrease the unique tendency of BPD patients to feel rejected even when socially included during a laboratory task. Objectives: This protocol outlines a double-blind, sham-controlled study evaluating the longitudinal effects of repeated anodal tDCS over the right ventrolateral prefrontal cortex (rVLPFC) on rejection-related emotions (RRE) during real-life social interactions in individuals with BPD. Methods: Sixty BPD patients will be randomized to receive real or sham tDCS across 10 daily sessions, coupled with an ecological momentary assessment (EMA) protocol capturing emotional and behavioral responses to real-life social interactions over four timepoints: baseline, during treatment, ten days post-treatment, and three months post-treatment. Primary outcomes include changes in RRE, with exploratory analyses examining feelings of social connection, aggressive tendencies, trust toward others, and interpersonal and affective dynamics. Multilevel modeling will assess temporal and group-level effects. Expected Results and Impact: This study aims to establish the efficacy of tDCS in reducing BPD patients’ negative emotional response in real-life social situations and to determine whether such effects are maintained in time. The findings could advance the clinical application of tDCS as an adjunctive intervention to alleviate social–emotional impairments in BPD, addressing gaps in current treatment approaches and guiding future research into the neural mechanisms of social emotion regulation. Full article

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

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2 pages, 816 KiB

Open AccessCorrection

Correction: Yeh et al. Electroacupuncture Reduced Fibromyalgia-Pain-like Behavior through Inactivating Transient Receptor Potential V1 and Interleukin-17 in Intermittent Cold Stress Mice Model. Brain Sci. 2024, 14, 869

by Yu-An Yeh, Hsien-Yin Liao, I-Han Hsiao, Hsin-Cheng Hsu and Yi-Wen Lin

Brain Sci. 2025, 15(5), 529; https://doi.org/10.3390/brainsci15050529 - 20 May 2025

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Abstract

In the original publication [...] Full article

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8 pages, 478 KiB

Open AccessArticle

A Pilot Study on the Influence of Self-Paced Auditory Cues and Preferred Music on Gait in Persons with Parkinson’s Disease

by Maddie Brant, Callan Barrick, Lindsay Muno and Elizabeth Stegemoller

Brain Sci. 2025, 15(5), 528; https://doi.org/10.3390/brainsci15050528 - 20 May 2025

Viewed by 402

Abstract

Background: Gait disturbance in Parkinson’s Disease (PD) significantly impacts quality of life and is not completely mitigated by dopaminergic treatment. Auditory cueing has been shown to help improve certain aspects of gait, but its effects when matched to individuals’ preferred walking rate [...] Read more.

Background: Gait disturbance in Parkinson’s Disease (PD) significantly impacts quality of life and is not completely mitigated by dopaminergic treatment. Auditory cueing has been shown to help improve certain aspects of gait, but its effects when matched to individuals’ preferred walking rate remain unexplored. Methods: Nine individuals with PD walked at their preferred rate across a GAITRite^® mat under three separate conditions: self-paced, metronome-cued, and music-cued. Spatiotemporal gait measures were collected and analyzed using repeated measures ANOVAs and post-hoc paired-samples t-tests. Results: A main effect of condition was revealed for step width (F = 3.533, p = 0.054, η_p² = 0.306), with reduced step width revealed during the music-cued condition. Post-hoc analysis revealed no significance (p > 0.063). Conclusions: The trend in step width data suggests a potential benefit of music cueing for enhancing gait stability in persons with PD. Results of this pilot study provide valuable framework for future research and the development of therapeutic interventions to enhance gait stability, reduce fall risk, and improve overall quality of life. Full article

(This article belongs to the Special Issue Focusing on the Rhythmic Interventions in Movement Disorders)

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19 pages, 1609 KiB

Open AccessArticle

A Lumped Parameter Modelling Study of Idiopathic Intracranial Hypertension Suggests the CSF Formation Rate Varies with the Capillary Transmural Pressure

by Grant A. Bateman and Alexander R. Bateman

Brain Sci. 2025, 15(5), 527; https://doi.org/10.3390/brainsci15050527 - 20 May 2025

Viewed by 693

Abstract

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R [...] Read more.

Background: Idiopathic intracranial hypertension (IIH) is, by definition, of unknown cause. Davson’s equation indicates that the increased intracranial pressure (ICP) found in IIH could be due to an increase in the CSF formation rate (CSF_fr), the CSF outflow resistance (R_out) or the venous sinus pressure. Studies simultaneously measuring the ICP and sagittal sinus pressures in IIH suggest that there is either a reduction in the R_out and/or the CSF_fr. The latter suggests that the increased venous pressure can be the only variable causing this disease process. A study maintaining the ICP at zero showed a significantly elevated CSF_fr in this disease. The purpose of the current study is to define the most feasible explanation for these findings and to suggest a viable pathophysiology for IIH. Methods: A lumped parameter vascular model, originally developed to study normal pressure hydrocephalus, was extended to investigate IIH. The model used the simultaneously obtained ICP and sagittal sinus pressure measurements from five experiments published in the literature to estimate the CSF_fr and the capillary transmural pressure (TMP). The assumptions made during this study were those of a normal mean arterial pressure, a normal total R_out and a normal blood flow rate. Results: When the CSF formation rates were plotted against the estimated capillary transmural pressures, a straight line was returned, suggesting that the CSF_fr and capillary TMP are related. Conclusions: The novel findings of this study suggest that the CSF_fr in IIH varies with the capillary TMP. A reduced capillary TMP in IIH can moderate the ICP if there is net CSF absorption across the capillaries. This would require the blood–brain barrier (BBB) to be disrupted. The model suggests that drugs which stabilise the BBB may trigger IIH by blocking CSF absorption across the capillaries, increasing the apparent CSF formation rate back toward normal and increasing the ICP. Anaemia will promote IIH by increasing the cerebral blood flow, the capillary TMP and the CSF_fr. Full article

(This article belongs to the Section Neurosurgery and Neuroanatomy)

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28 pages, 566 KiB

Open AccessPerspective

Cognitive Behavioural Therapy (CBT) for Managing Tinnitus, Hyperacusis, and Misophonia: The 2025 Tonndorf Lecture

by Hashir Aazh

Brain Sci. 2025, 15(5), 526; https://doi.org/10.3390/brainsci15050526 - 19 May 2025

Viewed by 1257

Abstract

Cognitive behavioural therapy (CBT) is an evidence-based intervention for managing distress associated with tinnitus, hyperacusis, and misophonia. This paper summarises key points from the 2025 Tonndorf Lecture presented at the third World Tinnitus Congress and the 14th International Tinnitus Seminar in Poland. The [...] Read more.

Cognitive behavioural therapy (CBT) is an evidence-based intervention for managing distress associated with tinnitus, hyperacusis, and misophonia. This paper summarises key points from the 2025 Tonndorf Lecture presented at the third World Tinnitus Congress and the 14th International Tinnitus Seminar in Poland. The lecture addressed (1) the theoretical foundations of CBT for these conditions, (2) clinical evidence on CBT delivered by psychologists, audiologists, and digital self-help, and (3) the proportion of patients who may benefit from CBT. Research demonstrates that CBT can effectively reduce distress related to tinnitus, hyperacusis, and misophonia. Both psychologist- and audiologist-delivered CBT approaches have demonstrated significant improvements in reducing the impact of tinnitus, hyperacusis, and misophonia on patients’ quality of life, while guided internet-based CBT also demonstrates positive outcomes. Unguided internet-based CBT is also effective, though it faces challenges such as higher dropout rates. Despite these promising results, not all patients experience the same level of benefit. Some continue to experience distress even after completing CBT, highlighting the need for alternative or complementary interventions and ongoing support. This paper estimates that approximately 1 in 52 individuals with tinnitus require CBT, indicating that while tinnitus is relatively common, the need for intensive therapy is comparatively small. To enhance treatment outcomes, future research should compare the effectiveness of psychologist- and audiologist-delivered CBT, explore hybrid models that combine face-to-face and digital interventions, and address challenges with internet-based CBT, particularly for hyperacusis and misophonia. Furthermore, incorporating neuroimaging and physiological measures in future randomised controlled trials could provide objective insights into the neural mechanisms underlying symptom improvement, ultimately helping to refine CBT interventions. Identifying characteristics of non-responders to CBT may also guide the development of more tailored therapeutic approaches. Full article

(This article belongs to the Section Behavioral Neuroscience)

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24 pages, 436 KiB

Open AccessSystematic Review

Physical, Cognitive, Social, and Functional Health Correlates of Major Depressive Disorder Subtypes: A Systematic Review

by Jen E. McKeough, Christopher F. Sharpley, Kirstan A. Vessey, Vicki Bitsika, Rebecca J. Williams, G. Lorenzo Odierna and Ian D. Evans

Brain Sci. 2025, 15(5), 525; https://doi.org/10.3390/brainsci15050525 - 19 May 2025

Viewed by 673

Abstract

Background/Objectives: Major Depressive Disorder (MDD) is a neuropsychiatric disorder affecting nearly 200 million people worldwide. While it has broad health effects, relatively little is known about how these vary across MDD ‘subtypes’, which reflect distinct symptom profiles. This systematic review examined the methods [...] Read more.

Background/Objectives: Major Depressive Disorder (MDD) is a neuropsychiatric disorder affecting nearly 200 million people worldwide. While it has broad health effects, relatively little is known about how these vary across MDD ‘subtypes’, which reflect distinct symptom profiles. This systematic review examined the methods used to define several MDD subtypes and their associations with physical, cognitive, social, and functional health outcomes. Methods: A systematic search of PubMed was conducted in accordance with PRISMA 2020 guidelines to identify peer-reviewed studies published in English between 2014 and 2025. The final search was conducted on 21 January 2025. Studies were included if they examined adults with MDD subtypes and reported health-related outcomes. Risk of bias was assessed using the Newcastle–Ottawa Scale. A narrative synthesis was conducted due to heterogeneity in the subtype definitions and outcome measures. Results: Sixteen studies were included. Atypical and melancholic depression were most consistently associated with metabolic dysfunction, higher BMI, and a greater waist circumference. Melancholic depression was frequently associated with cognitive deficits, though results varied. Cognitive impairments were also observed in DSM-defined atypical depression, particularly in attention, vigilance, and social cognition. Anxious and melancholic depression may be associated with more severe social and functional impairment compared to other subtypes. However, the findings were limited by inconsistent definitions and outcome measures. Conclusions: Some subtypes, particularly atypical, melancholic, and anxious depression, are differentially associated with specific patterns of impairment, though inconsistencies limit firm conclusions. Registration: This review was retrospectively registered with the Open Science Framework (OSF): No specific funding was received. Full article

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

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24 pages, 641 KiB

Open AccessArticle

Partner-Inflicted Brain Injury: Intentional, Concurrent, and Repeated Traumatic and Hypoxic Neurologic Insults

by Julianna M. Nemeth, Clarice Decker, Rachel Ramirez, Luke Montgomery, Alice Hinton, Sharefa Duhaney, Raya Smith, Allison Glasser, Abigail (Abby) Bowman, Emily Kulow and Amy Wermert

Brain Sci. 2025, 15(5), 524; https://doi.org/10.3390/brainsci15050524 - 19 May 2025

Viewed by 772

Abstract

(1) Background: Traumatic brain injury (TBI) is caused from rapid head acceleration/deceleration, focal blows, blasts, penetrating forces, and/or shearing forces, whereas hypoxic–anoxic injury (HAI) is caused through oxygen deprivation events, including strangulation. Most service-seeking domestic violence (DV) survivors have prior mechanistic exposures that [...] Read more.

(1) Background: Traumatic brain injury (TBI) is caused from rapid head acceleration/deceleration, focal blows, blasts, penetrating forces, and/or shearing forces, whereas hypoxic–anoxic injury (HAI) is caused through oxygen deprivation events, including strangulation. Most service-seeking domestic violence (DV) survivors have prior mechanistic exposures that can lead to both injuries. At the time of our study, some evidence existed about the exposure to both injuries over the course of a survivor’s lifetime from abuse sources, yet little was known about their co-occurrence to the same survivor within the same episode of physical intimate partner violence (IPV). To better understand the lived experience of service-seeking DV survivors and the context in which partner-inflicted brain injury (PIBI) is sustained, we sought to understand intentional brain injury (BI) exposures that may need to be addressed and accommodated in services. Our aims were to 1. characterize the lifetime co-occurrence of strangulation and intentional head trauma exposures from all abuse sources to the same survivor and within select physical episodes of IPV and 2. establish the lifetime prevalence of PIBI. (2) Methods: Survivors seeking DV services in the state of Ohio in the United States of America (U.S.) completed interview-administered surveys in 2019 (n = 47). Community-based participatory action approaches guided all aspects of the study development, implementation, and interpretation. (3) Results: The sample was primarily women. Over 40% reported having Medicaid, the government-provided health insurance for the poor. Half had less than a postsecondary education. Over 80% of participants presented to DV services with both intentional head trauma and strangulation exposures across their lifetime from intimate partners and other abuse sources (i.e., child abuse, family violence, peer violence, sexual assault, etc.), though not always experienced at the same time. Nearly 50% reported an experience of concurrent head trauma and strangulation in either the first or last physical IPV episode. Following a partner’s attack, just over 60% reported ever having blacked out or lost consciousness—44% experienced a loss of consciousness (LOC) more than once—indicating a conservative estimate of a probable brain injury by an intimate partner. Over 80% of service-seeking DV survivors reported either a LOC or two or more alterations in consciousness (AICs) following an IPV attack and were classified as ever having a partner-inflicted brain injury. (4) Conclusions: Most service-seeking IPV survivors experience repetitive and concurrent exposures to abusive strangulation and head trauma through the life course and by intimate partners within the same violent event resulting in brain injury. We propose the use of the term partner-inflicted brain injury (PIBI) to describe the physiological disruption of normal brain functions caused by intentional, often concurrent and repeated, traumatic and hypoxic neurologic insults by an intimate partner within the context of ongoing psychological trauma, coercive control, and often past abuse exposures that could also result in chronic brain injury. We discuss CARE (Connect, Acknowledge, Respond, Evaluate), a brain-injury-aware enhancement to service delivery. CARE improved trauma-informed practices at organizations serving DV survivors because staff felt knowledgeable to address and accommodate brain injuries. Survivor behavior was then interpreted by staff as a “can’t” not a “won’t”, and social and functional supports were offered. Full article

(This article belongs to the Special Issue Shedding Light on the Hidden Epidemic of Violence and Brain Injury)

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36 pages, 3285 KiB

Open AccessReview

A Unified Framework for Alzheimer’s Disease Knowledge Graphs: Architectures, Principles, and Clinical Translation

by Jovana Dobreva, Monika Simjanoska Misheva, Kostadin Mishev, Dimitar Trajanov and Igor Mishkovski

Brain Sci. 2025, 15(5), 523; https://doi.org/10.3390/brainsci15050523 - 19 May 2025

Cited by 1 | Viewed by 876

Abstract

This review paper synthesizes the application of knowledge graphs (KGs) in Alzheimer’s disease (AD) research, based on two basic questions, as follows: what types of input data are available to construct these knowledge graphs, and what purpose the knowledge graph is intended to [...] Read more.

This review paper synthesizes the application of knowledge graphs (KGs) in Alzheimer’s disease (AD) research, based on two basic questions, as follows: what types of input data are available to construct these knowledge graphs, and what purpose the knowledge graph is intended to fulfill. We synthesize results from existing works to illustrate how diverse knowledge graph structures behave in different data availability settings with distinct application targets in AD research. By comparative analysis, we define the best methodology practices by data type (literature, structured databases, neuroimaging, and clinical records) and application of interest (drug repurposing, disease classification, mechanism discovery, and clinical decision support). From this analysis, we recommend AD-KG 2.0, which is a new framework that coalesces best practices into a unifying architecture with well-defined decision pathways for implementation. Our key contributions are as follows: (1) a dynamic adaptation mechanism that adapts methodological elements automatically according to both data availability and application objectives, (2) a specialized semantic alignment layer that harmonizes terminologies across biological scales, and (3) a multi-constraint optimization approach for knowledge graph building. The framework accommodates a variety of applications, including drug repurposing, patient stratification for precision medicine, disease progression modeling, and clinical decision support. Our system, with a decision tree structured and pipeline layered architecture, offers research precise directions on how to use knowledge graphs in AD research by aligning methodological choice decisions with respective data availability and application goals. We provide precise component designs and adaptation processes that deliver optimal performance across varying research and clinical settings. We conclude by addressing implementation challenges and future directions for translating knowledge graph technologies from research tool to clinical use, with a specific focus on interpretability, workflow integration, and regulatory matters. Full article

(This article belongs to the Section Neurodegenerative Diseases)

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16 pages, 1674 KiB

Open AccessArticle

Validation of a New Stress Induction Protocol Using Speech Improvisation (IMPRO)

by Marina Saskovets, Mykhailo Lohachov and Zilu Liang

Brain Sci. 2025, 15(5), 522; https://doi.org/10.3390/brainsci15050522 - 19 May 2025

Cited by 1 | Viewed by 507

Abstract

Background: Acute stress induction is essential in psychology research for understanding physiological and psychological responses. In this study, ‘acute stress’ refers to a short-term, immediate stress response—distinct from chronic, long-term stress exposure. Traditional methods, such as the Trier Social Stress Test (TSST), have [...] Read more.

Background: Acute stress induction is essential in psychology research for understanding physiological and psychological responses. In this study, ‘acute stress’ refers to a short-term, immediate stress response—distinct from chronic, long-term stress exposure. Traditional methods, such as the Trier Social Stress Test (TSST), have ecological validity and resource-efficiency limitations. This study introduces the Interactive Multitask Performance Response Observation (IMPRO) protocol, a novel stress-induction method utilizing speech improvisation in a dynamic and unpredictable social setting. Methods: Thirty-five healthy adults (aged 18–38 years; 19 males, 16 females) participated in the study. The IMPRO protocol consisted of three speech improvisation tasks with increasing cognitive and social stressors. Salivary cortisol was used as a biochemical marker of acute stress, while electrodermal activity (EDA) provided real-time autonomic arousal measurements. Stress responses were assessed using paired t-tests for cortisol levels and repeated-measures ANOVA for EDA variations across experimental stages. Results: Salivary cortisol levels significantly increased from baseline (M = 2.68 nM, SD = 0.99) to post-task (M = 3.54 nM, SD = 1.25, p = 0.001, Cohen’s d = 0.59), confirming hypothalamic–pituitary–adrenal (HPA) axis activation. EDA showed a significant rise during the anticipation phase (p < 0.001), peaking at the final task and decreasing during recovery (η² = 0.643). Conclusions: The IMPRO protocol effectively induces acute stress responses, providing a scalable, ecologically valid alternative to traditional stress paradigms. Its low-cost, adaptable design makes it ideal for research in psychology, neuroscience, and behavioral sciences. Future studies should explore its application in clinical populations and group settings. Full article

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

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12 pages, 5510 KiB

Open AccessArticle

Image Fusion of High-Resolution DynaCT and T2-Weighted MRI for Image-Guided Programming of dDBS

by Fadil Al-Jaberi, Matthias Moeskes, Martin Skalej, Melanie Fachet and Christoph Hoeschen

Brain Sci. 2025, 15(5), 521; https://doi.org/10.3390/brainsci15050521 - 19 May 2025

Viewed by 475

Abstract

Objectives: This study aimed to develop a semi-automated registration method for aligning preoperative non-contrast T2-weighted MRI with postoperative high-resolution cone-beam CT (DynaCT) in patients undergoing directional deep brain stimulation (dDBS) surgery targeting the subthalamic nucleus (STN). The aim was to facilitate image-guided programming [...] Read more.

Objectives: This study aimed to develop a semi-automated registration method for aligning preoperative non-contrast T2-weighted MRI with postoperative high-resolution cone-beam CT (DynaCT) in patients undergoing directional deep brain stimulation (dDBS) surgery targeting the subthalamic nucleus (STN). The aim was to facilitate image-guided programming of DBS devices and postoperative verification of the alignment of segmented contacts. Materials and Methods: A dataset of ten patients undergoing bilateral dDBS implantation was retrospectively collected, including DynaCT (acquired postoperatively) and non-contrast T2-weighted MRI (obtained preoperatively). A semi-automated registration method was used, employing manual initialization due to dissimilar anatomical information between DynaCT and T2-weighted MRI. Image visualization, initial alignment using a centered transformation initializer, and single-resolution image registration involving the Simple Insight Toolkit (SimpleITK) library were performed. Manual landmark-based alignment based on anatomical landmarks and evaluation metrics such as Target Registration Error (TRE) assessed alignment accuracy. Results: The registration method successfully aligned all images. Quantitative evaluation revealed an average of the mean TRE of 1.48 mm across all subjects, indicating satisfactory alignment quality. Multiplanar reformations (MPRs) based on electrode-oriented normal vectors visualized segmented contacts for accurate electrode placement. Conclusions: The developed method demonstrated successful registration between preoperative non-contrast T2-weighted MRI and postoperative DynaCT, despite dissimilar anatomical information. This approach facilitates accurate alignment crucial for DBS programming and postoperative verification, potentially reducing the programming time of the DBS. The study underscores the importance of image quality, manual initialization and semi-automated registration methods for successful multimodal image registration in dDBS procedures targeting the STN. Full article

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

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22 pages, 3487 KiB

Open AccessArticle

Voice-Evoked Color Prediction Using Deep Neural Networks in Sound–Color Synesthesia

by Raminta Bartulienė, Aušra Saudargienė, Karolina Reinytė, Gustavas Davidavičius, Rūta Davidavičienė, Šarūnas Ašmantas, Gailius Raškinis and Saulius Šatkauskas

Brain Sci. 2025, 15(5), 520; https://doi.org/10.3390/brainsci15050520 - 19 May 2025

Viewed by 638

Abstract

Background/Objectives: Synesthesia is an unusual neurological condition when stimulation of one sensory modality automatically triggers an additional sensory sensation in an additional unstimulated modality. In this study, we investigated a case of sound–color synesthesia in a female with impaired vision. After confirming a [...] Read more.

Background/Objectives: Synesthesia is an unusual neurological condition when stimulation of one sensory modality automatically triggers an additional sensory sensation in an additional unstimulated modality. In this study, we investigated a case of sound–color synesthesia in a female with impaired vision. After confirming a positive case of synesthesia, we aimed to determine the sound features that played a key role in the subject’s sound perception and color development. Methods: We applied deep neural networks and a benchmark of binary logistic regression to classify blue and pink synesthetically voice-evoked color classes using 136 voice features extracted from eight study participants’ voice recordings. Results: The minimum Redundancy Maximum Relevance algorithm was applied to select the 20 most relevant voice features. The recognition accuracy of 0.81 was already achieved using five features, and the best results were obtained utilizing the seventeen most informative features. The deep neural network classified previously unseen voice recordings with 0.84 accuracy, 0.81 specificity, 0.86 sensitivity, and 0.85 and 0.81 F1-scores for blue and pink classes, respectively. The machine learning algorithms revealed that voice parameters, such as Mel-frequency cepstral coefficients, Chroma vectors, and sound energy, play the most significant role. Conclusions: Our results suggest that a person’s voice’s pitch, tone, and energy affect different color perceptions. Full article

(This article belongs to the Special Issue Perceptual Learning and Cortical Plasticity)

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34 pages, 2495 KiB

Open AccessSystematic Review

Neurophysiological Approaches to Lie Detection: A Systematic Review

by Bewar Neamat Taha, Muhammet Baykara and Talha Burak Alakuş

Brain Sci. 2025, 15(5), 519; https://doi.org/10.3390/brainsci15050519 - 18 May 2025

Viewed by 792

Abstract

Background and Objectives: Lie detection is crucial in domains such as security, law enforcement, and clinical assessments. Traditional methods suffer from reliability issues and susceptibility to countermeasures. In recent years, electroencephalography (EEG) and particularly the Event-Related Potential (ERP) P300 component have gained prominence [...] Read more.

Background and Objectives: Lie detection is crucial in domains such as security, law enforcement, and clinical assessments. Traditional methods suffer from reliability issues and susceptibility to countermeasures. In recent years, electroencephalography (EEG) and particularly the Event-Related Potential (ERP) P300 component have gained prominence for identifying concealed information. This systematic review aims to evaluate recent studies (2017–2024) on EEG-based lie detection using ERP P300 responses, especially in relation to recognized and unrecognized face stimuli. The goal is to summarize commonly used EEG signal processing techniques, feature extraction methods, and classification algorithms, identifying those that yield the highest accuracy in lie detection tasks. Methods: This review followed PRISMA guidelines for systematic reviews. A comprehensive literature search was conducted using IEEE Xplore, Web of Science, Scopus, and Google Scholar, restricted to English-language articles from 2017 to 2024. Studies were included if they focused on EEG-based lie detection, utilized experimental protocols like Concealed Information Test (CIT), Guilty Knowledge Test (GKT), or Deceit Identification Test (DIT), and evaluated classification accuracy using ERP P300 components. Results: CIT with ERP P300 was the most frequently employed protocol. The most used preprocessing method was Bandpass Filtering (BPF), and the Discrete Wavelet Transform (DWT) emerged as the preferred feature extraction technique due to its suitability for non-stationary EEG signals. Among classification algorithms, Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and Convolutional Neural Networks (CNN) were frequently utilized. These findings demonstrate the effectiveness of hybrid and deep learning-based models in enhancing classification performance. Conclusions: EEG-based lie detection, particularly using the ERP P300 response to face recognition tasks, shows promising accuracy and robustness compared to traditional polygraph methods. Combining advanced signal processing methods with machine learning and deep learning classifiers significantly improves performance. This review identifies the most effective methodologies and suggests that future research should focus on real-time applications, cross-individual generalization, and reducing system complexity to facilitate broader adoption. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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16 pages, 496 KiB

Open AccessReview

Anti-NMDA Receptor Encephalitis: A Narrative Review

by Vlad Pădureanu, Dalia Dop, Rodica Pădureanu, Denisa Floriana Vasilica Pîrșcoveanu, Gabriela Olaru, Ioana Streata and Ana Maria Bugă

Brain Sci. 2025, 15(5), 518; https://doi.org/10.3390/brainsci15050518 - 18 May 2025

Viewed by 807

Abstract

Antibodies against the NR1 or NR2 subunits of the NMDA receptor are linked to anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, a type of encephalitis that mainly affects women. Clinicians who treat patients of all ages should be aware of this type of encephalitis since it [...] Read more.

Antibodies against the NR1 or NR2 subunits of the NMDA receptor are linked to anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, a type of encephalitis that mainly affects women. Clinicians who treat patients of all ages should be aware of this type of encephalitis since it may be a treatable differential for symptoms and indicators observed in neurology and psychiatric clinics. Auditory and visual hallucinations, delusions, altered behavior (often accompanied by agitation), reduced consciousness, motor disruption (from dyskinesia to catatonia), seizures, and autonomic dysfunction are typical clinical characteristics. In recent years, the incidence of autoimmune encephalitis diagnoses has markedly risen among adults, children, and adolescents. This fact is unequivocally connected to the dynamic evolution of novel diagnostic techniques and the advancement of medical knowledge. A specific variant of this illness is anti-NMDA receptor encephalitis. Psychiatrists frequently serve as the initial specialists to treat patients with this diagnosis, owing to the manifestation of psychiatric symptoms associated with the condition. The differential diagnosis is quite challenging and predominantly relies on the patient’s history and the manifestation of characteristic clinical signs. Given its high prevalence, anti-NMDA receptor encephalitis should be included in the differential diagnosis in routine psychiatric treatment. We provide an overview of the research on the condition, covering its prognosis, management, epidemiology, differential diagnosis, and clinical presentation. Full article

(This article belongs to the Special Issue Novel Insights into Neuroinflammation and Brain Disease)

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16 pages, 4737 KiB

Open AccessArticle

Co-Community Network Analysis Reveals Alterations in Brain Networks in Alzheimer’s Disease

by Xiaodong Wang, Zhaokai Zhang, Lingli Deng and Jiyang Dong

Brain Sci. 2025, 15(5), 517; https://doi.org/10.3390/brainsci15050517 - 18 May 2025

Viewed by 473

Abstract

Background: Alzheimer’s disease (AD) is a common neurodegenerative disease. Functional magnetic resonance imaging (fMRI) can be used to measure the temporal correlation of blood-oxygen-level-dependent (BOLD) signals in the brain to assess the brain’s intrinsic connectivity and capture dynamic changes in the brain. [...] Read more.

Background: Alzheimer’s disease (AD) is a common neurodegenerative disease. Functional magnetic resonance imaging (fMRI) can be used to measure the temporal correlation of blood-oxygen-level-dependent (BOLD) signals in the brain to assess the brain’s intrinsic connectivity and capture dynamic changes in the brain. In this study, our research goal is to investigate how the brain network structure, as measured by resting-state fMRI, differs across distinct physiological states. Method: With the research goal of addressing the limitations of BOLD signal-based brain networks constructed using Pearson correlation coefficients, individual brain networks and community detection are used to study the brain networks based on co-community probability matrices (CCPMs). We used CCPMs and enrichment analysis to compare differences in brain network topological characteristics among three typical brain states. Result: The experimental results indicate that AD patients with increasing disease severity levels will experience the isolation of brain networks and alterations in the topological characteristics of brain networks, such as the Somatomotor Network (SMN), dorsal attention network (DAN), and Default Mode Network (DMN). Conclusion: This work suggests that using different data-driven methods based on CCPMs to study alterations in the topological characteristics of brain networks would provide better information complementarity, which can provide a novel analytical perspective for AD progression and a new direction for the extraction of neuro-biomarkers in the early diagnosis of AD. Full article

(This article belongs to the Special Issue Understanding the Functioning of Brain Networks in Health and Disease)

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24 pages, 1188 KiB

Open AccessArticle

Impathy and Emotion Recognition: How Attachment Shapes Self- and Other-Focused Emotion Processing

by Dirk W. Eilert, Karin de Punder, Jeff Maerz, Johanna Dose, Manuela Gander, Philipp Mensah, Stefanie Neubrand, Josef Hinterhölzl and Anna Buchheim

Brain Sci. 2025, 15(5), 516; https://doi.org/10.3390/brainsci15050516 - 18 May 2025

Viewed by 1351

Abstract

Background/Objectives: Early attachment experiences and psychopathology both shape individuals’ emotion processing. However, the specific influence of adult attachment representations on self- (intrapersonal) and other-focused (interpersonal) emotion processing remains unclear, particularly in the context of personality disorders. This study examined how attachment representations (organized [...] Read more.

Background/Objectives: Early attachment experiences and psychopathology both shape individuals’ emotion processing. However, the specific influence of adult attachment representations on self- (intrapersonal) and other-focused (interpersonal) emotion processing remains unclear, particularly in the context of personality disorders. This study examined how attachment representations (organized vs. unresolved) modulate intrapersonal emotion perception (“impathy”) and interpersonal emotion recognition while accounting for personality pathology. Methods: Thirty-three adults (twenty-four patients with a personality disorder and nine healthy controls) were assessed for attachment representation using the Adult Attachment Projective Picture System (AAP). Emotion processing was measured via the Impathy Inventory and a facial emotion recognition task (READ-64). Group differences (organized vs. unresolved attachment; patients vs. controls) and correlations with the severity of unresolved attachment status were analyzed. Results: Patients with organized attachment representations did not differ from healthy controls in emotion recognition but showed significantly reduced impathy (M difference = −21.72, SE = 6.20, p = 0.002, 95% CI [−34.42, −9.01], d = −1.57). In contrast, patients with unresolved attachment exhibited impairments in both intrapersonal (M difference = −32.99, SE = 6.20, p < 0.001, 95% CI [−45.69, −20.29], d = −2.39) and interpersonal (M difference = −12.37, SE = 4.36, p = 0.008, 95% CI [−21.28, −3.46], d = −1.23) emotion processing compared to healthy controls. Furthermore, the severity of unresolved attachment status correlated with greater impairment in recognizing anger (r = −0.74, p = 0.004). Conclusions: An organized attachment representation may act as a protective factor, preserving interpersonal emotion recognition even in the presence of psychopathology. Conversely, an unresolved attachment constitutes an additional risk factor that exacerbates emotion processing impairments in the context of personality pathology. Attachment representation thus emerges as an active modulator of core emotion processes, with important implications for theory and targeted interventions in personality disorders. Full article

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

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20 pages, 1350 KiB

Open AccessReview

Autobiographical Memory: A Scoping Meta-Review of Neuroimaging Data Enlightens the Inconsistencies Between Theory and Experimentation

by Edoardo Donarelli, Cristina Civilotti, Giulia Di Fini, Gabriella Gandino and Alessia Celeghin

Brain Sci. 2025, 15(5), 515; https://doi.org/10.3390/brainsci15050515 - 18 May 2025

Viewed by 482

Abstract

Background/Objectives: Autobiographical memory (AM) is typically viewed in terms of comprising episodic (EAM) and semantic (SAM) components. Despite the emergence of numerous meta-analyses, the literature on these constructs remains fragmented. We aimed to summarize neural activations and to discuss the relations between constructs [...] Read more.

Background/Objectives: Autobiographical memory (AM) is typically viewed in terms of comprising episodic (EAM) and semantic (SAM) components. Despite the emergence of numerous meta-analyses, the literature on these constructs remains fragmented. We aimed to summarize neural activations and to discuss the relations between constructs based on theory and experimentation, while evaluating the consistency between literature sources and discussing the critical issues and challenges of current research. Methods: We conducted a scoping meta-review on AM, EAM, and SAM based on meta-analytic studies in five scientific databases (PubMed, Web of Science, Scopus, PsychInfo, and PsychArticles). No temporal or language limits were applied. Results: We included twelve meta-analyses on AM, EAM and SAM in healthy populations. The meta-analyses of AM and EAM actually investigated the same construct, leading to misinterpretation. The two available meta-analyses on SAM used two different operationalizations of the construct. Neural data about EAM were analyzed via mean rank classification, finding the most relevant areas in the posterior cingulate cortex, hippocampus, precuneus, temporo-parietal junction, angular gyrus, and medial prefrontal cortex. SAM was linked to the posterior and anterior cingulate cortexes, middle and inferior frontal gyri, thalamus, middle and superior temporal gyri, inferior frontal and fusiform gyri, and parahippocampal cortex. Conclusions: Variability in reported activation patterns persists, reflecting differences in methodology and assumptions. We propose the homogenization the notations of EAM and AM based on experimental practice. In this notation, AM does not have a separate experimental task nor activation pattern and may not indicate a separate construct but an array of its components. Full article

(This article belongs to the Section Neurotechnology and Neuroimaging)

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14 pages, 656 KiB

Open AccessArticle

A Randomized Controlled Trial Comparing Subcutaneous Preservation of Bone Flaps with Cryogenic Preservation of Bone Flaps for Cranioplasty in Cases of Traumatic Brain Injury

by Rachith Sridhar, Anil Kumar, Harendra Kumar, Abdul Vakil Khan, Abdul Hakeem, Deepak Kumar, Anurag Kumar and Majid Anwer

Brain Sci. 2025, 15(5), 514; https://doi.org/10.3390/brainsci15050514 - 17 May 2025

Viewed by 1825

Abstract

Background and objectives: Decompressive craniectomy (DC) is a surgical procedure, useful for relieving the intracranial pressure following trauma. Following reduction in cerebral oedema, the bone is placed back to cover the defect. During the interim period, the bone flap may be preserved using [...] Read more.

Background and objectives: Decompressive craniectomy (DC) is a surgical procedure, useful for relieving the intracranial pressure following trauma. Following reduction in cerebral oedema, the bone is placed back to cover the defect. During the interim period, the bone flap may be preserved using cryopreservation or in subcutaneous tissue. This leads to a need to determine the benefits and risks involved in preservation of bone flap in a subcutaneous pocket or conventional freezer following decompressive craniectomy in traumatic brain injury. Materials and methods: An open randomized controlled trial was conducted at a level one trauma centre from July 2023 to December 2024. Simple randomization was performed in order to allocate patients into the subcutaneous preservation group and the cryogenic preservation group. Patients underwent cranioplasty after 3 months and were followed up post-operatively for complications and Glasgow Outcome Scale assessment. Results: The study initially recruited a total of 158 patients, out of which 104 patients remained eligible for the final analysis. The patients with cryopreserved flaps were found to have a higher rate of surgical site infection (31.3%) as compared to those with subcutaneously preserved flaps (5.6%), with the differences being statistically significant (p < 0.001). Among the 87 patients who had a poorer Glasgow Outcome Scale (GOS) score before the intervention, 55 (63.2%) patients had at least some improvement in GOS over a period of one month. Conclusion: The use of subcutaneous preservation of bone is more beneficial in resource-limited settings as compared to conventional freezer storage. Full article

(This article belongs to the Special Issue New Advances in Surgical Treatment of Brain Injury)

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14 pages, 1322 KiB

Open AccessArticle

Examination of Psychotropic Medication Use Following Outpatient Behavioral Assessment and Treatment

by Maria G. Valdovinos, Melissa Trites and Janelle Ausenhus

Brain Sci. 2025, 15(5), 513; https://doi.org/10.3390/brainsci15050513 - 17 May 2025

Viewed by 430

Abstract

Background/Objectives: Psychotropic medications are often prescribed to treat challenging behavior in children with neurodevelopmental disorders. This study examined patterns of psychotropic medication use following outpatient behavioral assessment and treatment in children ages 2–16 years. Methods: Medication use at the time of behavioral assessments, [...] Read more.

Background/Objectives: Psychotropic medications are often prescribed to treat challenging behavior in children with neurodevelopmental disorders. This study examined patterns of psychotropic medication use following outpatient behavioral assessment and treatment in children ages 2–16 years. Methods: Medication use at the time of behavioral assessments, six months after the assessment, and a later follow-up time point (mean 25 months following the six-month time point, range 1 month to 41 months) were evaluated via a chart review. Alterations in psychotropic medication use were grouped into eight categories according to the type of medication change experienced. Care providers also completed a social validity survey rating their satisfaction with the assessment and interventions developed for their child. Results: This retrospective study revealed that children in this sample were more likely to experience starting a new medication and increases in the dose of psychotropic medication as time passed. Children were also less likely to remain on the same regimen of psychotropic medication as when they were first seen in the clinic. Additionally, although caregivers generally rated their experiences and outcomes with the behavioral clinic as favorable, additions and increases to psychotropic medication regimens still occurred. Conclusions: These findings are consistent with other reports of continued and increased prescribing of psychotropic medication across time in children with neurodevelopmental disorders, however, the results must be interpreted with caution given the small sample size which limits generalizability of these findings. Additionally, the lack of follow-up with the patients in this sample made it difficult to correlate changes in challenging behavior with psychotropic medication prescribing. Full article

(This article belongs to the Special Issue Advances in Psychopharmacology in Neurodevelopmental Disorders (NDDs))

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17 pages, 855 KiB

Open AccessArticle

The Influence of Transcranial Alternating Current Stimulation on the Excitability of the Unstimulated Contralateral Primary Motor Cortex

by Erik W. Wilkins, Richard J. Young, Ryder Davidson, Reese Krider, George Alhwayek, Jonathan A. Park, Armaan C. Parikh, Zachary A. Riley and Brach Poston

Brain Sci. 2025, 15(5), 512; https://doi.org/10.3390/brainsci15050512 - 17 May 2025

Viewed by 771

Abstract

Objectives: Transcranial alternating current stimulation (tACS) can enhance primary motor cortex (M1) excitability and improve motor skill when delivered unilaterally to the dominant hemisphere. However, the impact of tACS on contralateral M1 excitability both during and after application has not been studied. The [...] Read more.

Objectives: Transcranial alternating current stimulation (tACS) can enhance primary motor cortex (M1) excitability and improve motor skill when delivered unilaterally to the dominant hemisphere. However, the impact of tACS on contralateral M1 excitability both during and after application has not been studied. The purpose of this study was to examine the effects of tACS delivered to the dominant left M1 on the excitability of the unstimulated contralateral non-dominant right M1. Methods: This study implemented a double-blind, randomized, SHAM-controlled, within-subjects, crossover experimental design. Eighteen young adults completed a tACS condition and a SHAM condition on two different days in counterbalanced order with a week washout period between days. Transcranial magnetic stimulation (TMS) was utilized to assess excitability of the contralateral right M1 while tACS was delivered to the left M1. TMS was administered in five test blocks (termed Pre, D5, D10, D15, and Post) relative to a 20 min application of tACS (70 Hz, 1 mA current strength). The Pre and Post TMS test blocks were conducted before and immediately after tACS was applied to the left M1, whereas the TMS test blocks performed during tACS were completed at time points starting at the 5, 10, and 15 min marks of the 20 min stimulation period. The primary dependent variable was the 1 mV motor evoked potential (MEP) amplitude. MEP data were analyzed with a 2 condition (tACS, SHAM) × 5 test (Pre, D5, D10, D15, Post) within-subjects ANOVA. Results: The main effect for condition (p = 0.704) and condition × test interaction (p = 0.349) were both non-statistically significant. There was a significant main effect for test (p = 0.003); however, post hoc analysis indicated that none of the pairwise comparisons were statistically significant. Conclusions: Overall, the findings indicate that tACS applied to the left M1 does not significantly modulate contralateral right M1 excitability during or immediately after stimulation, at least when utilizing the present tACS parameters. Full article

(This article belongs to the Special Issue New Insights into Movement Generation: Sensorimotor Processes)

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10 pages, 202 KiB

Open AccessArticle

Interrater Reliability of the Occupational Therapy Anticipatory Awareness Test: A Performance-Based Cognitive Assessment

by Danielle Mahoney, Stephanie Alvarado and Rochelle Mendonca

Brain Sci. 2025, 15(5), 511; https://doi.org/10.3390/brainsci15050511 - 16 May 2025

Viewed by 393

Abstract

Background: Functional cognitive impairments caused by acquired brain injury (ABI) negatively impact an individual’s daily functioning. Impaired self-awareness can pose obstacles to task execution and participation. Traditional assessment methods for self-awareness lack a functional approach, highlighting the need for performance-based assessments such as [...] Read more.

Background: Functional cognitive impairments caused by acquired brain injury (ABI) negatively impact an individual’s daily functioning. Impaired self-awareness can pose obstacles to task execution and participation. Traditional assessment methods for self-awareness lack a functional approach, highlighting the need for performance-based assessments such as the Occupational Therapy Anticipatory Awareness Test (OTAAT). The purpose of this study was to establish the interrater reliability of the OTAAT in adults with ABI. Methods: This was a two-phase study. Phase One involved the recruitment of three participants with ABI, who then underwent OTAAT administration within a setting of their choosing. OTAAT performances were recorded. In Phase Two, ten occupational therapists assessed the Phase One participants’ performances using the OTAAT. Phase Two’s raters’ outcomes were obtained by research personnel. These data were then collected and analyzed by research staff to measure interrater reliability using the Intraclass Correlation Coefficient (ICC) via IBM Statistical Package for the Social Sciences (SPSS) software. A two-way random effect, absolute agreement, multiple-rater/measurement ICC was adopted for this study. Results: Data analysis demonstrated strong interrater reliability for the OTAAT, demonstrating its consistency to measure self-awareness in individuals with ABI across different raters. Specifically, the ICC values indicated strong agreement among raters in their assessment of participants’ self-awareness performance using the OTAAT. Conclusions: The OTAAT has strong interrater reliability and holds promise as a valuable addition to neurorehabilitation practice. This study demonstrates the reliability of the OTAAT as a tool for assessing self-awareness in the ABI population. Full article

(This article belongs to the Special Issue The Impact of Stroke on Functional Cognition and Rehabilitation Approaches)

12 pages, 319 KiB

Open AccessArticle

Superficial Neuromodulation in Dysautonomia in Women with Post-COVID-19 Condition: A Pilot Study

by Alberto Melián-Ortíz, Eduardo Zurdo-Sayalero, Sara Perpiñá-Martínez, Antonio Delgado-Lacosta, Carmen Jiménez-Antona, Josué Fernández-Carnero and Sofía Laguarta-Val

Brain Sci. 2025, 15(5), 510; https://doi.org/10.3390/brainsci15050510 - 16 May 2025

Viewed by 553

Abstract

Post-COVID-19 condition involves persistent symptoms after acute infection, often linked to dysautonomia, which affects heart rate variability, pain perception, fatigue, and sleep. Superficial neuromodulation has been proposed as a treatment. Objective: To assess the effects of superficial neuromodulation on symptoms, sleep quality, and [...] Read more.

Post-COVID-19 condition involves persistent symptoms after acute infection, often linked to dysautonomia, which affects heart rate variability, pain perception, fatigue, and sleep. Superficial neuromodulation has been proposed as a treatment. Objective: To assess the effects of superficial neuromodulation on symptoms, sleep quality, and autonomic function in post-COVID-19 condition patients. Methods: A pilot study was conducted based on a triple-blind randomized controlled trial methodology involving 16 female participants. The experimental group received neuromodulation, while the control group used a placebo device. The intervention spanned 15 sessions over two months. Primary outcomes included heart rate variability, pain threshold, cortisol levels, fatigue, sleep quality, and quality of life, analyzed using repeated-measures ANOVA. Results: Both groups improved over time. Heart rate variability (SDNN) increased in the experimental group (30.42 to 39.11 ms) but decreased in controls (31.88 to 28.73 ms) (p < 0.05). Pain threshold at C5–C6 improved in the experimental group (2.1 to 3.5 kg/cm²) but remained stable in controls (p = 0.032). Fatigue decreased significantly in both groups (p = 0.002). Sleep quality improved, with Pittsburgh Sleep Quality Index scores decreasing similarly in both groups. Cortisol levels increased, with a non-significant trend favoring controls. Conclusions: While improvements were seen, both groups benefited, suggesting a possible placebo effect. Superficial neuromodulation appears safe, but further studies with larger samples are needed to confirm efficacy. Full article

(This article belongs to the Special Issue Neuromodulation for Pain Management: Evidence of Safety and Efficacy)

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25 pages, 6137 KiB

Open AccessArticle

EEG-Based Seizure Detection Using Dual-Branch CNN-ViT Network Integrating Phase and Power Spectrograms

by Zhuohan Wang, Yaoqi Hu, Qingyue Xin, Guanghao Jin, Yazhou Zhao, Weidong Zhou and Guoyang Liu

Brain Sci. 2025, 15(5), 509; https://doi.org/10.3390/brainsci15050509 - 16 May 2025

Viewed by 547

Abstract

Background/Objectives: Epilepsy is a common neurological disorder with pathological mechanisms closely associated with the spatiotemporal dynamic characteristics of electroencephalogram (EEG) signals. Although significant progress has been made in epileptic seizure detection methods using time–frequency analysis, current research still faces challenges in terms of [...] Read more.

Background/Objectives: Epilepsy is a common neurological disorder with pathological mechanisms closely associated with the spatiotemporal dynamic characteristics of electroencephalogram (EEG) signals. Although significant progress has been made in epileptic seizure detection methods using time–frequency analysis, current research still faces challenges in terms of an insufficient utilization of phase information. Methods: In this study, we propose an effective epileptic seizure detection framework based on continuous wavelet transform (CWT) and a hybrid network consisting of convolutional neural network (CNN) and vision transformer (ViT). First, the raw EEG signals are processed by the CWT. Then, the phase spectrogram and power spectrogram of the EEG are generated, and they are sent into the designed CNN and ViT branches of the network to extract more discriminative EEG features. Finally, the features output from the two branches are fused and fed into the classification network to obtain the detection results. Results: Experimental results on the CHB-MIT public dataset and our SH-SDU clinical dataset show that the proposed framework achieves sensitivities of 98.09% and 89.02%, specificities of 98.21% and 95.46%, and average accuracies of 98.45% and 94.66%, respectively. Furthermore, we compared the spectral characteristics of CWT with other time–frequency transforms within the hybrid architecture, demonstrating the advantages of the CWT-based CNN-ViT architecture. Conclusions: These results highlight the outstanding epileptic seizure detection performance of the proposed framework and its significant clinical feasibility. Full article

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

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16 pages, 588 KiB

Open AccessStudy Protocol

The Effects of Endoscopic Third Ventriculostomy Versus Ventriculoperitoneal Shunt on Neuropsychological and Motor Performance in Patients with Idiopathic Normal Pressure Hydrocephalus—ENVENTOR-iNPH: Study Protocol

by Gianluca Scalia, Nicola Alberio, Pietro Trombatore, Mariangela Panebianco, Grazia Razza, Gianluca Galvano, Giovanni Federico Nicoletti and Francesca Graziano

Brain Sci. 2025, 15(5), 508; https://doi.org/10.3390/brainsci15050508 - 16 May 2025

Viewed by 710

Abstract

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cognitive decline, gait disturbances, and urinary incontinence. Surgical interventions such as ventriculoperitoneal shunt (VPS) and endoscopic third ventriculostomy (ETV) are the primary treatment options. While VPS is the standard of [...] Read more.

Background: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cognitive decline, gait disturbances, and urinary incontinence. Surgical interventions such as ventriculoperitoneal shunt (VPS) and endoscopic third ventriculostomy (ETV) are the primary treatment options. While VPS is the standard of care, ETV offers a minimally invasive alternative with potentially fewer complications. However, comparative evidence regarding their impact on cognitive, motor, and structural outcomes remains limited. This study, titled ENVENTOR-iNPH (endoscopic ventriculostomy versus shunt on neuropsychological and motor performance in patients with iNPH), aims to address this gap through a rigorously designed comparative protocol. Methods: This protocol is designed as a multicenter, randomized, controlled trial (ENVENTOR-iNPH) to compare the effects of ETV and VPS in patients diagnosed with iNPH. The study will enroll 100 patients aged 60 years or older, randomly assigned to undergo ETV (n = 50) or VPS (n = 50). Preoperative and postoperative evaluations will include comprehensive cognitive and motor assessments, standardized quality-of-life instruments, and advanced neuroimaging techniques such as MRI with flowmetry and diffusion tensor imaging (DTI). Functional outcomes will also be evaluated using navigated transcranial magnetic stimulation (nTMS) and wearable motion analysis systems. The objective of this study is to compare the efficacy and safety of ETV versus VPS in restoring cognitive and motor performance in patients with iNPH. Results: Primary outcomes include cognitive and motor function improvements. Secondary endpoints are surgical complications, hospital stay duration, and changes in quality of life. Neuroimaging will assess changes in white matter integrity and cerebrospinal fluid dynamics, while nTMS will provide insights into neuroplasticity and motor pathway recovery. ETV is hypothesized to demonstrate clinical outcomes comparable or superior to VPS, particularly in terms of complication reduction and hospital recovery metrics. Conclusions: The ENVENTOR-iNPH protocol establishes the framework for a comprehensive, multicenter study comparing ETV and VPS in iNPH patients. The findings from this initial study will inform the design of larger-scale multicenter trials, guide clinical decision making, and potentially position ETV as a preferred treatment option for eligible patients. Full article

(This article belongs to the Special Issue Editorial Board Collection Series: Insight into Neurosurgery)

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Open AccessReview

Emotion, Motivation, Reasoning, and How Their Brain Systems Are Related

by Edmund T. Rolls

Brain Sci. 2025, 15(5), 507; https://doi.org/10.3390/brainsci15050507 - 16 May 2025

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Abstract

A unified theory of emotion and motivation is updated in which motivational states are states in which instrumental goal-directed actions are performed to obtain anticipated rewards or avoid punishers, and emotional states are states that are elicited when the (conditioned or unconditioned) instrumental [...] Read more.

A unified theory of emotion and motivation is updated in which motivational states are states in which instrumental goal-directed actions are performed to obtain anticipated rewards or avoid punishers, and emotional states are states that are elicited when the (conditioned or unconditioned) instrumental reward or punisher is or is not received. This advances our understanding of emotion and motivation, for the same set of genes and associated brain systems can define the primary or unlearned rewards and punishers such as a sweet taste or pain, and the brain systems that learn to expect rewards or punishers and that therefore produce motivational and emotional states. It is argued that instrumental actions under the control of the goal are important for emotion, because they require an intervening emotional state in which an action is learned or performed to obtain the goal, that is, the reward, or to avoid the punisher. The primate including human orbitofrontal cortex computes the reward value, and the anterior cingulate cortex is involved in learning the action to obtain the goal. In contrast, when the instrumental response is overlearned and becomes a habit with stimulus–response associations, emotional states may be less involved. In another route to output, the human orbitofrontal cortex has effective connectivity to the inferior frontal gyrus regions involved in language and provides a route for declarative reports about subjective emotional states to be produced. Reasoning brain systems provide alternative strategies to obtain rewards or avoid punishers and can provide different goals for action compared to emotional systems. Full article

(This article belongs to the Special Issue Defining Emotion: A Collection of Current Models)

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Brain Sci., Volume 15, Issue 5 (May 2025) – 113 articles

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