Brain Sciences

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

The benefits of sport activity on cognition and especially on executive function development are well-known, and in recent years, several kinds of cognitive-motor training (CMT) have been proven effective in adults and older people. Less is known about possible CMT benefits in children. This study aims to confirm the positive influence played by CMTs on specific executive functions (planning abilities and visual search) in young soccer players. Twenty-four 10-year-old athletes were recruited and randomly assigned to the experimental (Exp) and control (Con) groups of 12 players. Both groups were trained for 10 weeks, twice a week (90 min per training), following standard soccer training (technical-tactical exercises). The Exp group, during the first training session of the week, in the last 22 min, performed the experimental treatment, which consisted of a psychokinetic CMT. Both groups were examined before and after the ten-week training using the Tower of London and WISC-IV cancellation tests. Results revealed that the Exp group, following treatment, reported significantly better scores than the Con group in all the cognitive measures. We concluded that the proposed CMT is more effective than motor training alone at improving planning abilities and visual search abilities, even in children. Full article

A range of professional figures are needed to preserve the quality of life of people with amyotrophic lateral sclerosis. This study aimed to explore the beginning of the care process as negotiated by people with amyotrophic lateral sclerosis, their caregivers, and healthcare professionals. We designed the study according to the constructivist Grounded Theory method, collecting data through open-ended, semi-structured interviews, employing theoretical sampling and constant comparison, and performing conceptual coding as data analysis. By naming the core category “off-beat interfacing”, we were able to show how the demands of the professionals concerned did not correspond to the ability of people with ALS and their proxies to process information, deal with requests, and be at ease in making decisions at the beginning of the shared care pathway. Three categories were generated: (i) navigating different paths, (ii) offering and experiencing a standard, non-personalized pathway, and (iii) anticipating decisions. The network of services must be organized according to guidelines, but must also contemplate a patient-family-centered approach that permits more personalized assistance. Full article

Compared to other primates, humans are late bloomers, with exceptionally long childhood and adolescence. The extensive developmental period of humans is thought to facilitate the learning processes required for the growth and maturation of the complex human brain. During the first two and a half decades of life, the human brain is a construction site, and learning processes direct its shaping through experience-dependent neuroplasticity. Formal and informal learning, which generates long-term and accessible knowledge, is mediated by neuroplasticity to create adaptive structural and functional changes in brain networks. Since experience-dependent neuroplasticity is at full force during school years, it holds a tremendous educational opportunity. In order to fulfill this developmental and learning potential, educational practices should be human-brain-friendly and “ride” the neuroplasticity wave. Neuroscience can inform educators about the natural learning mechanisms of the brain to support student learning. This review takes a neuroscientific lens to explore central concepts in education (e.g., mindset, motivation, meaning-making, and attention) and suggests two methods of using neuroscience as an educational tool: teaching students about their brain (content level) and considering the neuro-mechanisms of learning in educational design (design level). Full article

Purpose: This study aimed to detect differences in post-exercise brain activity between the left and right paddlers due to exercise by analyzing the resting-state electroencephalogram (EEG) power spectrum before and after exercise. Methods: Twenty-one right paddlers and twenty-two left paddlers completed a 1 km all-out test on a dragon boat ergometer, and their heart rate and exercise time were recorded. EEG signals were collected from superficial brain layers before and after exercise; then, the EEG power spectrum was extracted and compared in different frequency bands. In addition, the degree of lateralization in each brain region was assessed by the asymmetry index. Results: There was no significant difference in the power spectrum values and asymmetry indices between the left and right paddlers before rowing (p ˃ 0.05). However, after rowing, the left-paddlers group had significantly higher spectral power values in θ and α bands than the right-paddlers group (p < 0.05), and brain lateralization in both groups of athletes occurred mainly in the ipsilateral hemisphere of the frontal and central regions. Conclusion: The 1 km of rowing induced more brain activation in the left paddlers, and both left and right paddlers showed functional aggregation of hemispheric lateralization. Full article

Purpose: Retinal pigment epithelial (RPE) cells are highly specialized neural cells with several functions essential for vision. Progressive deterioration of RPE cells in elderly individuals can result in visual impairment and, ultimately, blinding disease. While human embryonic stem cell-derived RPE cell (hESC-RPE) growth conditions are generally harsher than those of cell lines, the subretinal transplantation of hESC-RPE is being clinically explored as a strategy to recover the damaged retina and improve vision. The cell-adhesion ability of the support is required for RPE transplantation, where pre-polarized cells can maintain specific functions on the scaffold. This work examined four typical biodegradable hydrogels as supports for hESC-RPE growth. Methods: Four biodegradable hydrogels were examined: gelatin methacryloyl (GelMA), hyaluronic acid methacryloyl (HAMA), alginate, and fibrin hydrogels. ARPE-19 and hESC-RPE cells were seeded onto the hydrogels separately, and the ability of these supports to facilitate adherence, proliferation, and homogeneous distribution of differentiated hESC-RPE cells was investigated. Furthermore, the hydrogel’s subretinal bio-compatibility was assessed in vivo. Results: We showed that ARPE-19 and hESC-RPE cells adhered and proliferated only on the fibrin support. The monolayer formed when cells reached confluency, demonstrating the polygonal semblance, and revealing actin filaments that moved along the cytoplasm. The expression of tight junction proteins at cell interfaces on the 14th day of seeding demonstrated the barrier function of epithelial cells on polymeric surfaces and the interaction between cells. Moreover, the expression of proteins crucial for retinal functions and matrix production was positively affected by fibrin, with an increment of PEDF. Our in vivo investigation with fibrin hydrogels revealed high short-term subretinal biocompatibility. Conclusions: The research of stem cell-based cell therapy for retinal degenerative diseases is more complicated than that of cell lines. Our results showed that fibrin is a suitable scaffold for hESC-RPE transplantation, which could be a new grafting material for tissue engineering RPE cells. Full article