Brain Sciences

Sleep–wake rhythm disturbances have a negative impact on attention. However, how it affects attention and whether the restoration of regular rhythms can restore attention are unclear. This study aims to explore the effects of sleep–wake rhythm disturbances on three subfunctions of attention (alertness, orientation, and executive control) and the restoration of regular rhythms on these functions. Twenty-one participants in the experimental group (who experienced sleep–wake rhythm disturbances for at least one month; aged 18–26) were required to sleep regularly following a sleep schedule, whereas 20 participants in the control group (who maintained regular sleep for at least three months; aged 19–22) received no manipulation of their sleep. All participants were assessed using the attention network test three times in six days. All of them wore spectrum activity monitors and kept sleep diaries every day. The results showed that the effects of alertness and executive control in the experimental group were significantly lower than those in the control group. After five days of regular sleep, the difference in the alertness effect between the two groups significantly decreased. These results suggested that under natural conditions, sleep–wake rhythm disturbances could negatively influence alertness and executive control, and a short period of restoring a regular rhythm has a recovery effect on alertness. Full article

Background: The number of elderly diabetic patients has been increasing recently, and these patients have a higher morbidity of dementia than those without diabetes. Diabetes is associated with an increased risk for the development of dementia in elderly individuals, which is a serious health problem. Objectives: The primary aim was to examine whether diabetes is a risk factor for dementia among elderly individuals. The secondary aim was to apply grey theory to integrate the results and how they relate to cognitive impairments in elderly diabetic patients and to predict which participants are at high risk of developing dementia. Methods: Two hundred and twenty patients aged 50 years or older who were diagnosed with diabetes mellitus were recruited. Information on demographics, disease characteristics, activities of daily living, Mini Mental State Examination, sleep quality, depressive symptoms, and health-related quality of life was collected via questionnaires. The grey relational analysis approach was applied to evaluate the relationship between the results and health outcomes. Results: A total of 13.6% of participants had cognitive disturbances, of whom 1.4% had severe cognitive dysfunction. However, with regard to sleep disorders, 56.4% had sleep disturbances of varying degrees from light to severe. Further investigation is needed to address this problem. A higher prevalence of sleep disturbances among diabetic patients translates to a higher degree of depressive symptoms and a worse physical and mental health-related quality of life. Furthermore, based on the grey relational analysis, the grey relation coefficient varies from 0.6217~0.7540. Among the subjects, Participant 101 had the highest value, suggesting a need for immediate medical care. In this study, we observed that 20% of the total participants, for whom the grey relation coefficient was 0.6730, needed further and immediate medical care. Full article

Encephalocraniocutaneous lipomatosis (ECCL; Haberland syndrome, #613001) is an extremely rare congenital disorder that is manifested by the involvement of the skin, eyes and central nervous system (CNS). We report two cases of children with ECCL diagnosis. First was an 8-year-old girl who presented with symptomatic epilepsy, cerebral palsy and developmental delay. In 2020, she was admitted to the hospital due to the exacerbation of paresis and intensified prolonged epileptic seizures, provoked by infection of the middle ear. Diagnostic imaging revealed radiological changes suggestive of ECCL, providing a reason for the diagnosis, despite the lack of skin and eye anomalies. The second child, a 14-year-old girl, was consulted for subtle clinical signs and epilepsy suspicion. Diagnostic imaging findings were similar, though less pronounced. Based on neuroradiological abnormalities typical for Haberland syndrome, the authors discuss possible ECCL diagnosis. Full article

Purpose: Children with Autism Spectrum Disorder (ASD) and Developmental Language Disorder (DLD) frequently face pragmatic impairments which may result in learning, socialization, and mental health difficulties, therefore early intervention is crucial. In Portugal, the Pragmatic Intervention Programme (PICP) has been recently developed and validated, but its effects are unknown. This study aims to determine the effects of the PICP on preschool-age children with ASD or DLD with pragmatic impairments. Methods: A non-randomized controlled trial has been conducted. The children (n = 20) were assigned to the intervention (n = 11) or the control group (waiting list) (n = 9). Each child attended 24 PICP-based intervention sessions provided by a Speech and Language Therapist in kindergarten. The primary outcome measure was a Goal Attainment Scale (GAS) rated by parents and kindergarten teachers. Secondary outcomes include parent/teacher-reported communication skills (Escala de Avaliação de Competências Comunicativas) and an assessment of the child’s general language ability (Teste de Linguagem—Avaliação da Linguagem Pré-Escolar). Results: GAS results show that all the children in the intervention group made progress. Statistically significant differences between pre- and post-intervention assessments were found for all secondary outcomes. Conclusions: The main findings suggest that the PICP improves language in preschool-age children with ASD and DLD with pragmatic difficulties. Further research is needed to analyse the effects of the PICP for each neurodevelopmental disorder individually. These results are crucial and will contribute to future research and evidence-based practice. Full article

Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of Ca²⁺-dependent signaling pathways in various cell types throughout the body. Its neuronal isoform CaMKIIa (alpha) centrally integrates physiological but also pathological glutamate signals directly downstream of glutamate receptors and has thus emerged as a target for ischemic stroke. Previous studies provided evidence for the involvement of CaMKII activity in ischemic cell death by showing that CaMKII inhibition affords substantial neuroprotection. However, broad inhibition of this central kinase is challenging because various essential physiological processes like synaptic plasticity rely on intact CaMKII regulation. Thus, specific strategies for targeting CaMKII after ischemia are warranted which would ideally only interfere with pathological activity of CaMKII. This review highlights recent advances in the understanding of how ischemia affects CaMKII and how pathospecific pharmacological targeting of CaMKII signaling could be achieved. Specifically, we discuss direct targeting of CaMKII kinase activity with peptide inhibitors versus indirect targeting of the association (hub) domain of CaMKIIa with analogues of g-hydroxybutyrate (GHB) as a potential way to achieve more specific pharmacological modulation of CaMKII activity after ischemia. Full article

The aim of this selective review paper is to clarify potential confusion when referring to the term proactive inhibitory control. Illustrated by a concise overview of the literature, we propose defining reactive inhibition as the mechanism underlying stopping an action. On a stop trial, the stop signal initiates the stopping process that races against the ongoing action-related process that is triggered by the go signal. Whichever processes finishes first determines the behavioral outcome of the race. That is, stopping is either successful or unsuccessful in that trial. Conversely, we propose using the term proactive inhibition to explicitly indicate preparatory processes engaged to bias the outcome of the race between stopping and going. More specifically, these proactive processes include either pre-amping the reactive inhibition system (biasing the efficiency of the stopping process) or presetting the action system (biasing the efficiency of the go process). We believe that this distinction helps meaningful comparisons between various outcome measures of proactive inhibitory control that are reported in the literature and extends to experimental research paradigms other than the stop task. Full article

Peripheral sensory nerve electrical stimulation (PES) excites the primary motor cortex and is expected to improve motor dysfunction post-stroke. However, previous studies have reported a variety of stimulus frequencies and stimulus duration settings, and the effects of these different combinations on primary motor cortex excitability are not clear. We aimed to clarify the effects of different combinations of stimulus frequency and stimulus duration of PES on the excitation of primary motor cortex. Twenty-one healthy individuals (aged > 18 years, right-handed, and without a history of neurological or orthopedic disorders) were included. Each participant experienced three different stimulation frequencies (1, 10, and 50 Hz) and durations (20, 40, and 60 min). Motor-evoked potentials (MEPs) were recorded pre- and post-PES. The outcome measure was the change in primary motor cortex excitability using the MEP ratio. We used a D-optimal design of experiments and response surface analysis to define the optimal combination within nine different settings inducing more satisfying responses. The combination of stimulation frequency and stimulation time that maximized the desirability value was 10 Hz and 40 min, respectively. The results of this study may provide fundamental data for more minimally invasive and effective implementation of PES in patients with stroke. Full article

Mild cognitive impairment (MCI) is considered to be the limit between the cognitive changes of aging and early dementia; thus, discriminating between participants with and without MCI is important. In the present study, we aimed to examine the differences in the cerebral oxyhemoglobin signal between individuals with and without MCI. The cerebral oxyhemoglobin signal was measured when the participants (young and elderly controls as well as patients with MCI) performed category fluency, finger tapping, and dual tasks using head-mounted near-infrared spectroscopy; the results were compared between the groups. The cerebral oxyhemoglobin signal trended toward the highest values during the category fluency task in young participants and during the finger-tapping task in elderly participants regardless of the MCI status. The area under the curve was approximately 0.5, indicating a low discrimination ability between elderly participants with and without MCI. The measurement of the blood flow in the prefrontal cortex may not accurately quantify cognitive and motor performance to detect MCI. Finger tapping may increase cerebral blood flow in individuals with and without MCI during the task. Full article

Objective: The virtual reality (VR)-based path integration task shows substantial promise in predicting dementia risk. However, the reliability and validity in healthy populations need further exploration. The present study investigates the relationship between task indicators and brain structures in a healthy population using a VR-based navigation task, particularly the entorhinal cortex (EC) and hippocampus. Methods: Sixty healthy adults were randomly recruited to perform a VR-based path integration task, the digit span task (DST), and an MRI scan. The indicators of the VR-based path integration task were calculated, including the absolute distance error (ADE), degree of angle deviation (DAD), degree of path deviation (DPD), and return time (Time). The reliability of the above indicators was then estimated using the split-half method and Cronbach’s alpha. Correlation and regression analyses were then performed to examine the associations between these indicators and age, general cognitive ability (DST), and brain structural measures. Results: ADE, DAD, and DPD showed reasonable split-half reliability estimates (0.84, 0.81, and 0.72) and nice Cronbach’s alpha estimates (0.90, 0.86, and 0.96). All indicators correlated with age and DST. ADE and DAD were sensitive predictors of hippocampal volume, and return time was a predictor of EC thickness. Conclusion: Our findings demonstrate that the VR-based path integration task exhibits good reliability and validity in the healthy population. The task indicators are age-sensitive, can capture working memory capacity, and are closely related to the integrity of individual EC and hippocampal structures. Full article

Fetal alcohol spectrum disorders (FASD) are prevalent neurodevelopmental disorders. Genetics have been shown to have a role in the severity of alcohol’s teratogenic effects on the developing brain. We previously identified recombinant inbred BXD mouse strains that show high (HCD) or low cell death (LCD) in the hippocampus following ethanol exposure. The present study aimed to identify gene networks that influence this susceptibility. On postnatal day 7 (3rd-trimester-equivalent), male and female neonates were treated with ethanol (5.0 g/kg) or saline, and hippocampi were collected 7hrs later. Using the Affymetrix microarray platform, ethanol-induced gene expression changes were identified in all strains with divergent expression sets found between sexes. Genes, such as Bcl2l11, Jun, and Tgfb3, showed significant strain-by-treatment interactions and were involved in many apoptosis pathways. Comparison of HCD versus LCD showed twice as many ethanol-induced genes changes in the HCD. Interestingly, these changes were regulated in the same direction suggesting (1) more perturbed effects in HCD compared to LCD and (2) limited gene expression changes that confer resistance to ethanol-induced cell death in LCD. These results demonstrate that genetic background and sex are important factors that affect differential cell death pathways after alcohol exposure during development that could have long-term consequences. Full article

Research on visual encoding models for functional magnetic resonance imaging derived from deep neural networks, especially CNN (e.g., VGG16), has been developed. However, CNNs typically use smaller kernel sizes (e.g., 3 × 3) for feature extraction in visual encoding models. Although the receptive field size of CNN can be enlarged by increasing the network depth or subsampling, it is limited by the small size of the convolution kernel, leading to an insufficient receptive field size. In biological research, the size of the neuronal population receptive field of high-level visual encoding regions is usually three to four times that of low-level visual encoding regions. Thus, CNNs with a larger receptive field size align with the biological findings. The RepLKNet model directly expands the convolution kernel size to obtain a larger-scale receptive field. Therefore, this paper proposes a mixed model to replace CNN for feature extraction in visual encoding models. The proposed model mixes RepLKNet and VGG so that the mixed model has a receptive field of different sizes to extract more feature information from the image. The experimental results indicate that the mixed model achieves better encoding performance in multiple regions of the visual cortex than the traditional convolutional model. Also, a larger-scale receptive field should be considered in building visual encoding models so that the convolution network can play a more significant role in visual representations. Full article

Transient epileptic amnesia (TEA) is a rare cause of acute amnestic syndromes (AAS), often misdiagnosed as transient global amnesia (TGA). We proposed a scoring system—the EPIlepsy AMNEsia (EPIAMNE) score—using quantitative EEG (qEEG) analysis to obtain a tool for differentiating TEA from TGA. We retrospectively reviewed clinical information and standard EEGs (stEEG) of 19 patients with TEA and 21 with TGA. We computed and compared Power Spectral Density, demonstrating an increased relative theta power in TGA. We subsequently incorporated qEEG features in EPIAMNE score, together with clinical and stEEG features. ROC curve models and pairwise ROC curve comparison were used to evaluate and compare the diagnostic accuracy for TEA detection of EPIAMNE score, presence of symptoms atypical for TGA (pSymAT) and identification of anomalies (interictal epileptiform or temporal focal spiky transients) at stEEG (PosEEG). Area Under the Curve (AUC) of EPIAMNE score revealed to be higher than PosEEG and pSymAT (AUC_EPIAMNE = 0.95, AUC_pSymAT = 0.85, AUC_PosEEG = 0.67) and this superiority proved to be statistically significant (p-value_{EPIAMNE-PosEEG} and p-value_{EPIAMNE-pSymAT} < 0.05). In conclusion, EPIAMNE score classified TEA with higher accuracy than PosEEG and pSymAT. This approach could become a promising tool for the differential diagnosis of AAS, especially for early TEA detection. Full article

Multiple studies support the relationship between ADHD and overweight/obesity in youth. Different mechanisms may be involved, such as temperamental and psychopathological factors. The aim of this study was to test the hypothesis that specific temperamental and psychopathological dimensions could mediate the relationship between ADHD and obesity. The sample included 100 children and adolescents (78 males and 22 females; age range 6 to 18 years; mean age 9.90 ± 2.5 years). The assessment procedure included Conners’ Parent Rating Scale—Long (CPRS-R:L) as the inclusion criterion for ADHD diagnosis, the Child Behavior Checklist (CBCL), a dimensional measure for psychopathology, and the Junior Temperament and Character Inventory, which describes four temperamental dimensions: novelty seeking (NS), harm avoidance (HA), reward dependence (RD), and persistence (P). While in the whole ADHD sample, the highest scores were found in NS and the lowest in P, ADHD with overweight/obesity, compared to ADHD with normal weight, showed higher HA and RD, lower NS, and higher CBCL Internalizing scores. These findings suggest that ADHD youth with overweight/obesity present specific temperamental and psychopathological features compared to those without overweight/obesity. If confirmed in larger samples, using a control group without ADHD, these temperamental and psychological features may be helpful for an earlier recognition of ADHD patients at higher risk for obesity, and may represent possible targets for temperament-based preventive interventions and tailored treatment programs. These features should be included in the routine assessment of children and adolescents with ADHD and/or are overweight/obese. Full article

Virtual reality (VR), a rapidly evolving technology that simulates three-dimensional virtual environments for users, has been proven to activate brain functions. However, the continuous alteration pattern of the functional small-world network in response to comprehensive three-dimensional stimulation rather than realistic two-dimensional media stimuli requires further exploration. Here, we aimed to validate the effect of VR on the pathways and network parameters of a small-world organization and interpret its mechanism of action. Fourteen healthy volunteers were selected to complete missions in an immersive VR game. The changes in the functional network in six different frequency categories were analyzed using graph theory with electroencephalography data measured during the pre-, VR, and post-VR stages. The mutual information matrix revealed that interactions between the frontal and posterior areas and those within the frontal and occipital lobes were strengthened. Subsequently, the betweenness centrality (BC) analysis indicated more robust and extensive pathways among hubs. Furthermore, a specific lateralized channel (O1 or O2) increment in the BC was observed. Moreover, the network parameters improved simultaneously in local segregation, global segregation, and global integration. The overall topological improvements of small-world organizations were in high-frequency bands and exhibited some degree of sustainability. Full article

The current study investigated the mental lexicon features of the Hakka-Mandarin dialect bilingual from two perspectives: the structural features of lexicons and the relations between lexicons. Experiment one used a semantic fluency task and complex-network analysis to observe the structural features of lexicons. Experiment two used a cross-language long-term repetition priming paradigm to explore the relations between lexicons, with three sub-experiments focusing on conceptual representation, lexical representation, and their relations, respectively. The results from experiment one showed that the dialect bilingual lexicons were small-world in nature, and the D2 (Mandarin) lexicon was better organized than the D1 (Hakka) lexicon. Experiment two found that D1 and D2 might have partially shared conceptual representations, separate lexical form representations, and partially shared lemma representations. Based on the findings, we tentatively proposed a two-layer activation model to simulate the lexicon features of dialect bilingual speakers. Full article

Introduction: microRNAs (miRNAs) are a class of non-coding RNAs playing a myriad of important roles in regulating gene expression. Of note, recent work demonstrated a critical role of miRNAs in the genesis and progression of brain arteriovenous malformations (bAVMs). Accordingly, here we examine miRNA signatures related to bAVMs and associated gene expression. In so doing we expound on the potential prognostic, diagnostic, and therapeutic significance of miRNAs in the clinical management of bAVMs. Methods: A PRISMA-based literature review was performed using PubMed/Medline database with the following search terms: “brain arteriovenous malformations”, “cerebral arteriovenous malformations”, “microRNA”, and “miRNA”. All preclinical and clinical studies written in English, regardless of date, were selected. For our bioinformatic analyses, miRWalk and miRTarBase machine learning algorithms were employed; the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was quired for associated pathways/functions. Results: four studies were ultimately included in the final analyses. Sequencing data consistently revealed the decreased expression of miR-18a in bAVM-endothelial cells, resulting in increased levels of vascular endodermal growth factor (VEGF), Id-1, matrix metalloproteinase, and growth signals. Our analyses also suggest that the downregulation of miR-137 and miR-195* within vascular smooth muscle cells (VSMCs) may foster the activation of inflammation, aberrant angiogenesis, and phenotypic switching. In the peripheral blood, the overexpression of miR-7-5p, miR-629-5p, miR-199a-5p, miR-200b-3p, and let-7b-5p may contribute to endothelial proliferation and nidus development. The machine learning algorithms employed confirmed associations between miRNA-related target networks, vascular rearrangement, and bAVM progression. Conclusion: miRNAs expression appears to be critical in managing bAVMs’ post-transcriptional signals. Targets of microRNAs regulate canonical vascular proliferation and reshaping. Although additional scientific evidence is needed, the identification of bAVM miRNA signatures may facilitate the development of novel prognostic/diagnostic tools and molecular therapies for bAVMs. Full article

Background: Laser interstitial thermal therapy (LITT) has emerged as a minimally invasive treatment modality for ablation of low-grade glioma (LGG) and radiation necrosis (RN). Objective: To evaluate the efficacy, safety, and survival outcomes of patients with radiographically presumed recurrent or newly diagnosed LGG and RN treated with LITT. Methods: The neuro-oncological database of a quaternary center was reviewed for all patients who underwent LITT for management of LGG between 1 January 2013 and 31 December 2020. Clinical data including demographics, lesion characteristics, and clinical and radiographic outcomes were collected. Kaplan–Meier analyses comprised overall survival (OS) and progression-free survival (PFS). Results: Nine patients (7 men, 2 women; mean [SD] age 50 [16] years) were included. Patients underwent LITT at a mean (SD) of 11.6 (8.5) years after diagnosis. Two (22%) patients had new lesions on radiographic imaging without prior treatment. In the other 7 patients, all (78%) had surgical resection, 6 (67%) had intensity-modulated radiation therapy and chemotherapy, respectively, and 4 (44%) had stereotactic radiosurgery. Two (22%) patients had lesions that were wild-type IDH1 status. Volumetric assessment of preoperative T1-weighted contrast-enhancing and T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences yielded mean (SD) lesion volumes of 4.1 (6.5) cm³ and 26.7 (27.9) cm³, respectively. Three (33%) patients had evidence of radiographic progression after LITT. The pooled median (IQR) PFS for the cohort was 52 (56) months, median (IQR) OS after diagnosis was 183 (72) months, and median (IQR) OS after LITT was 52 (60) months. At the time of the study, 2 (22%) patients were deceased. Conclusions: LITT is a safe and effective treatment option for management of LGG and RN, however, there may be increased risk of permanent complications with treatment of deep-seated subcortical lesions. Full article

Early rehabilitation with the right intensity contributes to the physical recovery of stroke survivors. In clinical practice, physicians determine whether the training intensity is suitable for rehabilitation based on patients’ narratives, training scores, and evaluation scales, which puts tremendous pressure on medical resources. In this study, a lightweight facial expression recognition algorithm is proposed to diagnose stroke patients’ training motivations automatically. First, the properties of convolution are introduced into the Vision Transformer’s structure, allowing the model to extract both local and global features of facial expressions. Second, the pyramid-shaped feature output mode in Convolutional Neural Networks is also introduced to reduce the model’s parameters and calculation costs significantly. Moreover, a classifier that can better classify facial expressions of stroke patients is designed to improve performance further. We verified the proposed algorithm on the Real-world Affective Faces Database (RAF-DB), the Face Expression Recognition Plus Dataset (FER+), and a private dataset for stroke patients. Experiments show that the backbone network of the proposed algorithm achieves better performance than Pyramid Vision Transformer (PvT) and Convolutional Vision Transformer (CvT) with fewer parameters and Floating-point Operations Per Second (FLOPs). In addition, the algorithm reaches an 89.44% accuracy on the RAF-DB dataset, which is higher than other recent studies. In particular, it obtains an accuracy of 99.81% on the private dataset, with only 4.10M parameters. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) is consistently associated with a host of social problems, such as victimization and difficulties in maintaining close friendships. These problems are not limited to offline relations but also manifest in the online social world, as previous research shows that ADHD is associated with problematic use of social media. Given the ubiquitous nature of social media, the goal of the current review is to understand why adolescents with ADHD demonstrate more problematic social media use than their typically developing peers. To this end, we provide a narrative review on the evidence for the link between ADHD and social media use, and consequently present an integrative framework, which encompasses neurobiological mechanisms (i.e., imbalance theory of brain development and dual pathway model of ADHD) and social mechanisms, including influences from peers and parents. We conclude that empirical work shows most consistent evidence for the link between problematic social media use and ADHD (symptoms), while intensity of social media use is also associated with several other behaviors and outcomes. Finally, we hypothesize how existing interventions for ADHD may work on the identified mechanisms and provide at-hand clinical recommendations for therapists working with adolescents with ADHD who exhibit problematic social media use. Full article