Brain Sci., Volume 14, Issue 3 (March 2024) – 109 articles

Changes in cerebrospinal fluid (CSF) dynamics can have adverse effects on neuronal function. We hypothesized that patients with hypoxic–ischemic brain injury (HIBI) showing poor neurological outcomes after cardiac arrest (CA) would exhibit changes in CSF dynamics, leading to abnormalities in gas diffusion within the CSF. Therefore, we investigated the prognostic value of the CSF partial pressure of carbon dioxide (PcsfCO₂) in CA survivors who underwent targeted temperature management (TTM). We retrospectively analyzed the 6-month neurological outcomes, CSF, and arterial blood gas parameters of 67 CA survivors. Patients were divided into good and poor neurological outcome groups, and the predictive value of PcsfCO₂ for poor neurological outcomes was assessed using receiver operating characteristic curve analysis. Among all patients, 39 (58.2%) had poor neurological outcomes. Significant differences in PcsfCO₂ levels between the groups were observed, with lower PcsfCO₂ levels on Day 1 showing the highest predictive value at a cutoff of 30 mmHg (area under the curve, sensitivity, and specificity were 0.823, 77.8%, and 79.0%, respectively). These results suggest that PcsfCO₂ might serve not only as a unique marker for the severity of hypoxic–ischemic brain injury (HIBI), independent of extracorporeal CO₂ levels, but also as an objective indicator of changes in CSF dynamics. This study highlights the potential prognostic and diagnostic utility of PcsfCO₂ during TTM in CA survivors, emphasizing its importance in evaluating CSF dynamics and neurological recovery post CA. However, larger multicenter studies are warranted to address potential limitations associated with sample size and outcome assessment methods. Full article

In this paper, we discuss how the clustering analysis technique can be applied to analyze functional magnetic resonance imaging (fMRI) time-series data in the context of glioblastoma (GBM), a highly heterogeneous brain tumor. The precise characterization of GBM is challenging and requires advanced analytical approaches. We have synthesized the existing literature to provide an overview of how clustering algorithms can help identify unique patterns within the dynamics of GBM. Our review shows that the clustering of fMRI time series has great potential for improving the differentiation between various subtypes of GBM, which is pivotal for developing personalized therapeutic strategies. Moreover, this method proves to be effective in capturing temporal changes occurring in GBM, enhancing the monitoring of disease progression and response to treatment. By thoroughly examining and consolidating the current research, this paper contributes to the understanding of how clustering techniques applied to fMRI data can refine the characterization of GBM. This article emphasizes the importance of incorporating cutting-edge data analysis techniques into neuroimaging and neuro-oncology research. By providing a detailed perspective, this approach may guide future investigations and boost the development of tailored therapeutic strategies for GBM. Full article

Introduction: The middle cranial fossa (MCF) approach is a well-established procedure in surgery of the internal auditory canal, as well as with the retrosigmoid and translabyrinthine approaches. It is commonly used in the hearing-preserving microsurgery of small vestibular schwannomas (VS). The debate about the “best” approach for the microsurgery of small VS without contact to the brainstem is controversial. It has been stated that the MCF approach leads to irreversible damage to the temporal lobe, which may be evident in follow-up magnet resonance imaging (MRI) as gliosis in up to 70% of patients. Materials and Methods: This study represents a retrospective chart analysis conducted at a tertiary university hospital. Here, 76 postoperative MRIs were re-evaluated by an experienced neuroradiologist and compared with the preoperative images. Temporal lobe gliosis was classified on an ordinal scale as absent, slight, moderate or severe. Occurrence of gliosis was matched to the clinical predictors (tumor stage, tumor volume, sex, age, and side). Results: No case of severe or moderate gliosis was found in the patient group. Slight gliosis of the temporal lobe was rare and was only detected in four patients (5%). There was no relation between clinical predictors and the incidence of gliosis. Conclusions: In our cohort, postoperative MR imaging did not reveal relevant damage to the temporal lobe parenchyma. This confirms the safe concept of microsurgery of small tumors via the middle fossa approach. The severe glioses described in other studies may be caused by a forced insertion of the retractor or by more extended approaches. However, further prospective neurocognitive studies seem to be necessary in order to assess functional changes in the temporal lobe. Full article

Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research. Full article

Neurological involvement following coronavirus disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an anti-inflammatory molecule) and luteolin (an anti-oxidant) have shown promising results as neuroinflammation antagonists. The aim of this study was to describe cognitive impairment in patients with post-COVID-19 treated with co-ultraPEALut. The Montreal Cognitive Assessment (MoCA), the Prospective–Retrospective Memory Questionnaire (PRMQ), the Fatigue Severity Scale (FSS), and a subjective assessment were administered at baseline and after 10 months. Patients treated with co-ultraPEALut were retrospectively compared with controls. Twenty-six patients treated with co-ultraPEALut showed a significant improvement in PRMQ (T0: 51.94 ± 10.55, T1: 39.67 ± 13.02, p < 0.00001) and MoCA raw score (T0: 25.76 ± 2.3, T1: 27.2 ± 2, p 0.0260); the MoCA-adjusted score and the FSS questionnaires also showed an improvement, even though it was not statistically significant; and 80.77% of patients reported a subjective improvement. In the control subjects (n = 15), the improvement was not as pronounced (PRMQ T0: 45.77 ± 13.47, T1: 42.33 ± 16.86, p 0.2051; FSS T0: 4.95 ± 1.57, T1: 4.06 ± 1.47, p 0.1352). Patients treated with co-ultraPEALut and corticosteroids were not statistically different from those treated with co-ultraPEALut alone. Neuro-post-COVID-19 patients treated with co-ultraPEALut scored better than controls in MoCA and PRMQ questionnaires after 10 months: this may support the importance of neuroinflammation modulation for neuro-long-COVID-19. Full article

Quantifying saccadic eye movements can assist in identifying dysfunctional brain networks in both healthy and diseased people. Infrared Oculography is a simple and non-invasive approach to capturing and quantifying saccades, providing information that might aid in diagnosis and outcome assessments. The effect of spinal manipulation on quantified saccadic performance parameters has not been fully studied despite known post-manipulative effects on the brain and brainstem regions controlling them. This case study investigates spinal manipulation’s immediate and long-term effects on saccadic eye movements by quantifying the saccades of a male patient diagnosed with post-concussion syndrome. The patient performed horizontal saccades that were quantified before and immediately following cervical spinal manipulation both at the case study’s start and following a 2-week interim, during which the subject received six manipulative treatments. Immediate and long-term post-manipulative effects were observed, and the results revealed various post-manipulative effects across all quantified parameters in addition to between right and leftward saccades. The immediate post-manipulative effect was greatest at the case study’s onset, while the long-term right and leftward saccadic symmetry were most affected. The observations in this case study demonstrate that cervical spinal manipulation influences saccadic eye movements, providing new insights into its central neurological effects and therapeutic applications beyond its most commonly known use in pain management. More importantly, it encourages scientists to undertake further clinical investigations on wider scales. Full article

Background: Speech-sound disorders (SSD) have been linked to auditory processing difficulties, and auditory processing disorders (APD) have been related to phonological awareness and literacy development. To this date, there has not been a systematic literature review investigating the results of psychophysiology and language assessments related to SSD and APD in children. Methods: The literature search was conducted in PubMed, Medline EBSCO, and Scopus to identify studies with children diagnosed/suspected of having APDs and SSDs. The quality of methodology in the selected articles was evaluated with the Newcastle Ottawa Scale. Results: Seven out of 378 relevant studies met the selection criteria. The findings were summarized for children with SSD and APD based on (a) metalinguistic and literacy skills, (b) cognitive abilities, and (c) temporal processing abilities. Three articles indicated that children with APD and SSD exhibit lower temporal task accuracy and reaction time. In two studies, children with SSD exhibited lower scores in discrimination, sequencing, and recall of brief stimuli in rapid succession. Conclusions: This review revealed associations between SSD severity and APD that may underline low performance in metalinguistic skills. Diagnostic assessments have been proposed based on the review to adequately identify children with SSD and APD and provide useful information for more suitable intervention. Full article

Neuroinflammation contributes to the pathophysiology of major depressive disorder (MDD) by inducing neuronal excitability via dysregulation of microglial brain-derived neurotrophic factor (BDNF), Na-K-Cl cotransporter-1 (NKCC1), and K-Cl cotransporter-2 (KCC2) due to activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling. Allosteric modulation of α7 nAChRs has not been investigated on BDNF, KCC2, and NKCC1 during LPS-induced depressive-like behavior. Therefore, we examined the effects of PNU120596, an α7 nAChR positive allosteric modulator, on the expression of BDNF, KCC2, and NKCC1 in the hippocampus and prefrontal cortex using Western blot analysis, immunofluorescence assay, and real-time polymerase chain reaction. The effects of ANA12, a TrkB receptor antagonist, on LPS-induced cognitive deficit and depressive-like behaviors were determined using the Y-maze, tail suspension test (TST), and forced swim test (FST). Pharmacological interactions between PNU120596 and ANA12 were also examined. Experiments were conducted in male C57BL/6J mice. LPS administration (1 mg/kg) resulted in increased expression of BDNF and the NKCC1/KCC2 ratio and decreased expression of KCC2 in the hippocampus and prefrontal cortex. PNU120596 pretreatment (4 mg/kg) attenuated the LPS-induced increase in the expression of BDNF and NKCC1/KCC2 ratio and the reduction in KCC2 expression in these brain regions. In addition, ANA12 (0.25 or 0.50 mg/kg) reduced the LPS-induced cognitive deficit and depressive-like behaviors measured by a reduced spontaneous alternation in the Y-maze and increased immobility duration in TST and FST. Coadministration of PNU120596 (1 mg/kg) and ANA12 (0.25 mg/kg) prevented the LPS-induced cognitive deficit and depressive-like behaviors. Overall, PNU120596 prevented the LPS-induced depressive-like behavior by likely decreasing neuronal excitability via targeting microglial α7 nAChR in the hippocampus and prefrontal cortex. Full article

To evaluate the efficacy of perivascular sympathectomy in managing adventitia layer-related long-segment tubular stenosis of cervical segment (C1) internal carotid arteries (ICAs) in a cohort where conventional medical and endovascular interventions were not viable options, we retrospectively analyzed 20 patients (8 males, 12 females, aged 41–63 years) who underwent perivascular sympathectomy for long-segment (>5 cm) tubular cervical ICA stenosis (non-atherosclerotic, non-intima related, and nondolichoarteriopathic) between 2017 and 2023. The procedure aimed to alleviate symptoms such as hemiparesis, pulsatile tinnitus, and migraines associated with transient ischemic attacks (TIAs). Preoperative and postoperative symptoms were assessed, and patient follow-up was conducted by MR angiography and perfusion studies. Postoperatively, 10 out of 11 migraine sufferers (90.9%) reported complete cessation of symptoms, while one patient (9.09%) experienced reduction in frequency and intensity. In cases of tinnitus, six out of nine patients (66.6%) reported complete resolution, two (22.2%) had reduced symptoms, and one (11.1%) saw no change. Regarding motor function, all 12 patients (100%) with initial hemiparesis (30–40% loss of motor function) showed complete recovery postoperatively. There was no TIA attack among the patients after the procedure in the mean two-year follow-up. Perivascular sympathectomy has shown promising results in alleviating symptoms and preventing recurrent cerebrovascular events in long-segment tubular stenosis of cervical ICAs. Full article

The Food Finding Test (FFT) olfactory paradigm without overnight food deprivation examined olfaction in aged (16-months-old) animals. Ethograms of three goal-directed behaviors towards hidden food (sniffing, finding and eating) elicited in male and female 3xTg-AD mice for Alzheimer’s disease (AD) and their age-matched C57BL/6 wild-type counterparts with normal aging were meticulously analyzed with the support of video recordings. The new FFT protocol elicited longer ethograms than previously reported with the standard deprivation protocol. However, it was sensitive when identifying genotype- and sex-dependent olfactory signatures for the temporal patterns of slow sniffing, finding, and eating in AD and males, but it had a striking consistency in females. The impact of forced social isolation was studied and it was found to exert sex-dependent modifications of the ethogram, mostly in males. Still, in both sexes, a functional derangement was detected since the internal correlations among the behaviors decreased or were lost under isolated conditions. In conclusion, the new paradigm without overnight deprivation was sensitive to sex (males), genotype (AD), and social context (isolation-dependent changes) in its ethogram and functional correlation. At the translational level, it is a warning about the impact of isolation in the advanced stages of the disease, paying notable attention to the male sex. Full article

(1) Background: Gangliogliomas are rare tumors accounting for about 0.4% of all central nervous system tumors. They are usually located in the temporal lobes of children and young adults, though such tumors in the infratentorial region and adult-age patients rarely reported. (2) Methods: A systematic review on ganglioglioma with infratentorial location in the adult population was conducted in accordance with the PRISMA guidelines. A total of 275 articles were found, and 23 were included. Demographic data, the location and histology of the lesion, pre-operative neurological status, the type of surgery, recurrence, radiotherapy/chemotherapy adjuvant treatments, neurological outcomes and follow-up information were collected. We also presented an illustrative case. (3) Results: A total of 27 patients were included. In 51%, the location was the cerebellum; in 40%, it was the fourth ventricle; in 11%, it was brainstem; and in 4%, it was the cerebellopontine angle. STR was performed in 44%, GTR in 26% and biopsy in 15% of the cases. Adjuvant radiotherapy was found in 22% of cases. Disease recurrence occurred in 15% of patients between 1 and 12 months after surgery with a diagnosis of high-grade ganglioglioma, while in six cases, no disease recurrence was documented. (4) Conclusions: Infratentorial glioneuronal tumors are rare findings in the adult population. Histopathological characterization does not seem to fully reflect their true behavior. Future studies are warranted for better characterizing histopathological findings and treatment. Full article

Sensory processing is a fundamental aspect of the nervous system that plays a pivotal role in the cognitive decline observed in older individuals with dementia. The “sensory diet”, derived from sensory integration theory, may provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain in individuals with dementia. Therefore, this review aimed to investigate the current knowledge regarding the sensory diet and its potential application to dementia. This review encompassed an extensive search across multiple databases, including PubMed, Google Scholar, covering articles published from 2010 to 2023. Keywords such as “sensory integration”, “sensory modulation”, “healthy aging”, and “dementia” were utilized to identify relevant studies. The types of materials retrieved included peer-reviewed articles, systematic reviews, and meta-analyses, ensuring a comprehensive overview of the current research landscape. This article offers a comprehensive exploration of the effectiveness of sensory diets such as tactile stimulation, auditory therapies, and visual interventions, which have demonstrated noteworthy efficacy in addressing challenges linked to aging and dementia. Research findings consistently report positive outcomes, such as improved cognitive function, elevated emotional well-being, and enhanced overall quality of life in older individuals. Furthermore, we found that the integration of sensory diets with the metaverse, augmented reality, and virtual reality opens up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. Therefore, we conclude that customized sensory diets, based on interdisciplinary cooperation and leveraging technological advancements, are effective in optimizing sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia. Full article

Diabetes is a chronic metabolic condition associated with high levels of blood glucose which leads to serious damage to the heart, kidney, eyes, and nerves. Elevated blood glucose levels damage brain function and cognitive abilities. They also lead to various neurological and neuropsychiatric disorders, including chronic neurodegeneration and cognitive decline. High neuronal glucose levels can cause drastic neuronal damage due to glucose neurotoxicity. Astrocytes, a type of glial cell, play a vital role in maintaining brain glucose levels through neuron–astrocyte coupling. Hyperglycemia leads to progressive decline in neuronal networks and cognitive impairment, contributing to neuronal dysfunction and fostering a neurodegenerative environment. In this review, we summarize the various connections, functions, and impairments of glial cells due to metabolic dysfunction in the diabetic brain. We also summarize the effects of hyperglycemia on various neuronal functions in the diabetic brain. Full article

About one-third of stroke survivors present unilateral spatial neglect (USN) that negatively impacts the rehabilitation outcome. We reported the study protocol and usability results of an eye-tracking (ET) biofeedback immersive virtual reality (iVR) protocol. Healthy controls and stroke patients with and without USN underwent a single session of the three iVR tasks. The system usability scale (SUS), adverse events (AEs), and ET data were collected and analyzed via parametric analysis. Twelve healthy controls (six young adults and six older adults) and seven patients with a diagnosis of single ischemic stroke (four without USN and three with confirmed diagnosis of USN) completed the usability investigation. SUS results showed good acceptability of the system for healthy controls and stroke patients without USN. ET results showed a lower performance for patients with USN concerning healthy controls and stroke patients without USN, in particular in the exploration of the left visual field. The results showed that the proposed iVR-ET biofeedback protocol is a safe and well-tolerated technique in patients with USN. The real-time feedback can induce a performance response supporting its investigation such as a treatment approach. Full article

As games have been applied across various fields, including education and healthcare, numerous new games tailored to each field have emerged. Therefore, understanding user behavior has become crucial in securing the right players for each type of game. This study provides valuable insights for improving game development by measuring the electroencephalography (EEG) of game users and classifying the frequency of game usage. The multimodal mobile brain-body imaging (MOBI) dataset was employed for this study, and the frequency of game usage was categorized into ”often” and ”sometimes”. To achieve decent classification accuracy, a novel bimodal Transformer architecture featuring dedicated channels for the frontal (AF) and temporal (TP) lobes is introduced, wherein convolutional layers, self-attention mechanisms, and cross-attention mechanisms are integrated into a unified model. The model, designed to differentiate between AF and TP channels, exhibits functional differences between brain regions, allowing for a detailed analysis of inter-channel correlations. Evaluated through five-fold cross-validation (CV) and leave-one-subject-out cross-validation (LOSO CV), the proposed model demonstrates classification accuracies of 88.86% and 85.11%, respectively. By effectively classifying gameplay frequency, this methodology provides valuable insights for targeted game participation and contributes to strategic efforts to develop and design customized games for player acquisition. Full article

Objective: To explore the association between the apolipoprotein E (APOE) genotype and objectively assessed cognitive function. Methods: In this cross-sectional study, 537 participants underwent a neuropsychological assessment for cognitive function and blood testing for APOE genotype. Based on cognitive test results, participants were stratified into two cohorts: Cognitively Unimpaired participants (CU) and Cognitively Impaired participants (CI). The CI group was further divided into Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Furthermore, we conducted age stratification, categorizing participants into three age groups: age 1: <65 years, age 2: 65–75 years, and age 3: >75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-β levels were measured in a cohort of 294 participants to investigate potential interactions involving ε4 carrier status, diagnosis, sex, or plasma markers. Results: The APOE genotypic distribution among the 537 participants was characterized as follows: ε2/ε2 (5 participants), ε2/ε3 (67), ε2/ε4 (13), ε3/ε3 (330), ε3/ε4 (113), and ε4/ε4 (9). Allele frequencies were: ε3 at 78.21%, ε4 at 13.41%, and ε2 at 8.38%. Notably, the ε4 carrier frequency was markedly elevated in the AD group at 81.8% when compared to MCI at 32.8% and CU at 21.3% (p < 0.05). Within the Cognitively Unimpaired (CU) cohort, the sole discernible contrast between ε4+ and ε4− emerged in STT-B (p < 0.05). Within the CI group, ε4 carriers showed statistically poorer scores as compared to non-ε4 carriers in several cognitive tests (p < 0.05). Age stratification result revealed that, among ε4 carriers, cognitive function scores within the age 3 group were significantly inferior to those of age 1 and age 2 groups (p < 0.05). Plasma amyloid-β detection was applied to the 294 participants. We tested plasma amyloid-β (Aβ42) and plasma amyloid-β (Aβ40) levels and calculated the Aβ42/Aβ40 ratio. We found that among female ε4 carriers, both Aβ42 and the Aβ42/Aβ40 ratio were notably lower than their male counterparts (p < 0.05). Conclusions: The ε3/ε3 was the most prevalent among participants, succeeded by ε3/ε4 and ε2/ε3. The least prevalent were ε2/ε4, ε4/ε4, and ε2/ε2 genotypes. The ε3 was predominant, followed by the ε4 and ε2. Individuals with the ε4 allele exhibited significant cognitive impairment, with an especially high prevalence in AD group at 81.8%. The study unveils a pronounced correlation between the ε4 allele and cognitive deficits, implying its potential role in the advancement and severity of cognitive disorders, notably Alzheimer’s disease. Cognitive function declines with age in individuals carrying the ε4, and women are more affected by ε4. Full article

Caffeine (CAF), a prevalent psychoactive stimulant, is believed to potentially enhance cognitive ability. However, studies on the effects of various doses are limited and yield inconsistent results, particularly in female athletes. Therefore, we aimed to assess the association between three different dosages of CAF intake (low, moderate, and high) and cognitive skills in female athletes with low CAF consumption. This study had a randomized, crossover, double-blind design in which each athlete performed four experimental sessions after ingesting either a placebo (PLAC), 3 mg·kg⁻¹ of CAF (3 mg of CAF), 6 mg·kg⁻¹ of CAF (6 mg of CAF), or 9 mg·kg⁻¹ of CAF (9 mg of CAF) with an in-between washout period of at least 72 h. Following a 60 min window post-capsule consumption, fourteen female athletes (age: 17.4 ± 0.8 years) were assessed through various cognitive tests, namely, simple reaction time (SRT), choice reaction time (CRT), and attentional task (AT) tests, along with the mental rotation test (MRT). Additionally, they were required to complete a questionnaire about the undesirable side effects of CAF. Our results indicated that, compared to those of PLAC, the SRT, CRT, and AT performance were significantly improved following the administration of both 3 mg of CAF and 6 mg of CAF. While the greatest enhancement was observed after consuming ₃ mg of _CAF, no significant differences were found between the effects of 3 mg and 6 mg of CAF. Interestingly, MRT performance did not improve with any of the CAF dosages. Moreover, the ingestion of 9 mg of CAF did not enhance cognitive skills and was linked to the highest occurrence of CAF-related side effects. In conclusion, our results highlight the recommendation for a low CAF dosage of 3 mg·kg⁻¹, in contrast to a higher dose of 6 mg·kg⁻¹ or 9 mg·kg⁻¹ of CAF, to enhance various aspects of cognitive performance in female athletes with low CAF consumption without adverse side effects. Full article

Terahertz radiation falls within the spectrum of hydrogen bonding, molecular rotation, and vibration, as well as van der Waals forces, indicating that many biological macromolecules exhibit a strong absorption and resonance in this frequency band. Research has shown that the terahertz radiation of specific frequencies and energies can mediate changes in cellular morphology and function by exciting nonlinear resonance effects in proteins. However, current studies have mainly focused on the cellular level and lack systematic studies on multiple levels. Moreover, the mechanism and law of interaction between terahertz radiation and neurons are still unclear. Therefore, this paper analyzes the mechanisms by which terahertz radiation modulates the nervous system, and it analyzes and discusses the methods by which terahertz radiation modulates neurons. In addition, this paper reviews the laws of terahertz radiation’s influence on neuronal morphology and kinetic properties and discusses them in detail in terms of terahertz radiation frequency, energy, and time. In the future, the safety of the terahertz radiation system should be considered first to construct the safety criterion of terahertz modulation, and the spatial resolution of the terahertz radiation system should be improved. In addition, the systematic improvement of the laws and mechanisms of terahertz modulation of the nervous system on multiple levels is the key to applying terahertz waves to neuroscience. This paper can provide a platform for researchers to understand the mechanism of the terahertz–nervous system interaction, its current status, and future research directions. Full article

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive–emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients’ daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individuals. Full article

Spatial navigation ability is essential for independent living, and it relies on complex cognitive and motor processes that are vulnerable to decline in persons with multiple sclerosis (pwMS). The role of mobility in the physical act of navigation has been well documented; however, its association with cognitive processing that supports efficient navigation and recall of the environment is unknown. This study examined the relation between clinical mobility function and spatial navigation ability in pwMS. In a clinical sample of 43 individuals with relapsing-remitting MS (M_PDDS = 2; age 25–67 years), we assessed spatial navigation ability in a virtual Morris water maze that allowed for active search by controlling a joystick while seated at a computer, and subsequent free recall of environment details. Individuals with worse mobility (measured by slower forward and backward walking) traveled less efficient virtual navigation routes to the goal location and recalled fewer accurate details of the environment. A stratified analysis by disability revealed moderate–strong correlations for those with a low level of disability, and effects were attenuated in individuals with a high level of disability. Given that the virtual navigation task was performed while seated, evidence of any correlation with mobility suggests differences in navigation ability that cannot be ascribed to general walking impairment, and instead suggests a role for mobility impairment to modify cognitive processing supporting navigation in pwMS. Full article

This study investigates the sex-specific role of the Hypothalamic–Pituitary–Gonadal axis in Alzheimer’s disease progression, utilizing ADNI1 data for 493 individuals, analyzing plasma levels of gonadotropic and sex hormones, and examining neurodegeneration-related brain structures. We assessed plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P4), and testosterone (T), along with volumetric measures of the hippocampus, entorhinal cortex, and hypothalamic subunits, to explore their correlation with Alzheimer’s disease markers across different cognitive statuses and sexes. Significant cognitive status effects were observed for all volumetric measures, with a distinct sex-by-cognitive status interaction for hypothalamic volume, indicating a decrease in males but not in females across cognitive impairment stages. Regression analyses showed specific hypothalamic subunit volume related to hormone levels, accounting for up to approximately 40% of the variance (p < 0.05). The findings highlight sex differences in neurodegeneration and hormonal regulation, suggesting potential for personalized treatments and advancing the understanding of Alzheimer’s disease etiology. Full article

Rapid neuronal inhibition in the brain is mediated by γ-aminobutyric acid (GABA) activation of GABA_A receptors. The GABRA5 gene, which encodes the α5 subunit of the GABA_A receptor, has been implicated in an aggressive subgroup of medulloblastoma (MB), a type of pediatric brain tumor. However, the possible role of GABA_A receptor subunits in glioma remains poorly understood. Here, we examined the expression of genes encoding GABA_A receptor subunits in different types of glioma, and its possible association with patient prognosis assessed by overall survival (OS). Data were obtained from the French and The Cancer Genome Atlas Brain Lower Grade Glioma (TCGA-LGG) datasets and analyzed for expression of GABA_A receptor subunit genes. OS was calculated using the Kaplan–Meier estimate. We found that genes GABRA2, GABRA3, GABRB3, GABRG1, and GABRG2 showed a significant association with OS, with higher gene expression indicating better prognosis. In patients with GBM, high expression of GABRA2 was associated with shorter OS, whereas, in contrast, higher levels of GABRB3 were associated with better prognosis indicated by longer OS. In patients with lower grade gliomas, GABRA3, GABRB3, GABRG1, and GABRG2, were associated with longer OS. High GABRB3 expression was related to longer survival when low grade glioma types were analyzed separately. Our results suggest an overall association between higher expression of most genes encoding GABA_A receptor subunits and better prognosis in different types of glioma. Our findings support the possibility that down-regulation of GABA_A receptors in glioma contributes to promoting tumor progression by reducing negative inhibition. These findings might contribute to further evaluation of GABA_A receptors as a therapeutic target in glioma. Full article

Alterations in sensory processing, a key component of autism spectrum disorder (ASD), have recently attracted increasing attention as they result in peculiar responses to sensory stimuli, possibly representing a risk factor for the development of somatic symptom disorder (SSD). Contextually, other features also associated with ASD, such as alexithymia, camouflaging and altered verbal, and non-verbal communication, have been suggested to represent risk factors for the occurrence and worsening of somatic symptomatology. The aim of this work was to review the available literature about the association between SSD and the autism spectrum. The results highlighted not only a higher prevalence of autistic features in patients suffering from SSD and a higher prevalence of reported somatic symptomatology in subjects with ASD but also how ASD subjects with co-occurrent somatic symptoms exhibit more severe autism-linked symptomatology. From the paper reviewed also emerged many shared features between the two conditions, such as alexithymia, altered sensitivity to sensory stimuli, cognitive inflexibility, intolerance of uncertainty, and an increased risk of experiencing stressful life events, which may provide an explanation for the correlation reported. Even though studies on the topic are still scant, the evidence reported suggests the importance of further assessing the correlation between the two disorders. Full article

Autism spectrum disorders (ASDs) encompass a broad group of neurodevelopmental disorders with varied clinical symptoms, all being characterized by deficits in social communication and repetitive behavior. Although the etiology of ASD is heterogeneous, with many genes involved, a crucial role is believed to be played by copy number variants (CNVs). The present study examines the role of copy number variation in the development of isolated ASD, or ASD with additional clinical features, among a group of 180 patients ranging in age from two years and four months to 17 years and nine months. Samples were taken and subjected to array-based comparative genomic hybridization (aCGH), the gold standard in detecting gains or losses in the genome, using a 4 × 180 CytoSure Autism Research Array, with a resolution of around 75 kb. The results indicated the presence of nine pathogenic and six likely pathogenic imbalances, and 20 variants of uncertain significance (VUSs) among the group. Relevant variants were more prevalent in patients with ASD and additional clinical features. Twelve of the detected variants, four of which were probably pathogenic, would not have been identified using the routine 8 × 60 k microarray. These results confirm the value of microarrays in ASD diagnostics and highlight the need for dedicated tools. Full article

Neurofilaments light chain (NfLs) are currently recognized as a marker of axonal injury and degeneration. Their measurement in biological fluids has a promising role in the diagnosis, prognosis, and monitoring of the therapeutic response in neurological diseases, including neurodegenerative dementias. In recent years, their relationship with clinical phenotypes and measures of disease severity has been extensively studied. Here, we reviewed studies investigating the association between NfLs and imaging measures of grey matter (GM) and white matter (WM) damage in neurodegenerative dementias. We identified a large number of studies investigating this association in Alzheimer’s disease (AD) and disorders of the frontotemporal dementia (FTD) spectrum. Results were heterogeneous, possibly due to different methodological approaches—both in NfL measurements and imaging analyses—and inclusion criteria. However, a positive association between NfL levels and GM atrophy, WM microstructural disruption, glucose hypometabolism, and protein accumulation emerged invariably, confirming the role of NfLs as a reliable biomarker for neurodegenerative dementias, albeit not specific. Full article

Emotion is one of the most important higher cognitive functions of the human brain and plays an important role in transaction processing and decisions. In traditional emotion recognition studies, the frequency band features in EEG signals have been shown to have a high correlation with emotion production. However, traditional emotion recognition methods cannot satisfactorily solve the problem of individual differences in subjects and data heterogeneity in EEG, and subject-independent emotion recognition based on EEG signals has attracted extensive attention from researchers. In this paper, we propose a subject-independent emotion recognition model based on adaptive extraction of layer structure based on frequency bands (BFE-Net), which is adaptive in extracting EEG map features through the multi-graphic layer construction module to obtain a frequency band-based multi-graphic layer emotion representation. To evaluate the performance of the model in subject-independent emotion recognition studies, extensive experiments are conducted on two public datasets including SEED and SEED-IV. The experimental results show that in most experimental settings, our model has a more advanced performance than the existing studies of the same type. In addition, the visualization of brain connectivity patterns reveals that some of the findings are consistent with previous neuroscientific validations, further validating the model in subject-independent emotion recognition studies. Full article

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood–brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood–brain barrier function. Full article

Objectives: The temporal and spatial information of electroencephalogram (EEG) signals is crucial for recognizing features in emotion classification models, but it excessively relies on manual feature extraction. The transformer model has the capability of performing automatic feature extraction; however, its potential has not been fully explored in the classification of emotion-related EEG signals. To address these challenges, the present study proposes a novel model based on transformer and convolutional neural networks (TCNN) for EEG spatial–temporal (EEG ST) feature learning to automatic emotion classification. Methods: The proposed EEG ST-TCNN model utilizes position encoding (PE) and multi-head attention to perceive channel positions and timing information in EEG signals. Two parallel transformer encoders in the model are used to extract spatial and temporal features from emotion-related EEG signals, and a CNN is used to aggregate the EEG’s spatial and temporal features, which are subsequently classified using Softmax. Results: The proposed EEG ST-TCNN model achieved an accuracy of 96.67% on the SEED dataset and accuracies of 95.73%, 96.95%, and 96.34% for the arousal–valence, arousal, and valence dimensions, respectively, for the DEAP dataset. Conclusions: The results demonstrate the effectiveness of the proposed ST-TCNN model, with superior performance in emotion classification compared to recent relevant studies. Significance: The proposed EEG ST-TCNN model has the potential to be used for EEG-based automatic emotion recognition. Full article