Brain Sci., Volume 14, Issue 5 (May 2024) – 87 articles

Diffusion tensor imaging (DTI) enables the assessment of changes in brain tissue microstructure during maturation and ageing. In general, patterns of cerebral maturation and decline render non-monotonic lifespan trajectories of DTI metrics with age, and, importantly, the rate of microstructural changes is heterochronous for various white matter fibres. Recent studies have demonstrated that diffusion kurtosis imaging (DKI) metrics are more sensitive to microstructural changes during ageing compared to those of DTI. In a previous work, we demonstrated that the Cohen’s d of mean diffusional kurtosis (d_MK) represents a useful biomarker for quantifying maturation heterochronicity. However, some inferences on the maturation grades of different fibre types, such as association, projection, and commissural, were of a preliminary nature due to the insufficient number of fibres considered. Hence, the purpose of this follow-up work was to further explore the heterochronicity of microstructural maturation between pre-adolescence and middle adulthood based on DTI and DKI metrics. Using the effect size of the between-group parametric changes and Cohen’s d, we observed that all commissural fibres achieved the highest level of maturity, followed by the majority of projection fibres, while the majority of association fibres were the least matured. We also demonstrated that d_MK strongly correlates with the maxima or minima of the lifespan curves of DTI metrics. Furthermore, our results provide substantial evidence for the existence of spatial gradients in the timing of white matter maturation. In conclusion, our data suggest that DKI provides useful biomarkers for the investigation of maturation spatial heterogeneity and heterochronicity. Full article

Background: Patients with supratentorial cavernous malformations (SCMs) commonly present with seizures. First-line treatments for cavernoma-related epilepsy (CRE) include conservative management (antiepileptic drugs (AEDs)) and surgery. We compared seizure outcomes of CRE patients after early (≤6 months) vs. delayed (>6 months) surgery. Methods: We compared outcomes of CRE patients with SCMs surgically treated at our large-volume cerebrovascular center (1 January 2010–31 July 2020). Patients with 1 sporadic SCM and ≥1-year follow-up were included. Primary outcomes were International League Against Epilepsy (ILAE) class 1 seizure freedom and AED independence. Results: Of 63 CRE patients (26 women, 37 men; mean ± SD age, 36.1 ± 14.6 years), 48 (76%) vs. 15 (24%) underwent early (mean ± SD, 2.1 ± 1.7 months) vs. delayed (mean ± SD, 6.2 ± 7.1 years) surgery. Most (32 (67%)) with early surgery presented after 1 seizure; all with delayed surgery had ≥2 seizures. Seven (47%) with delayed surgery had drug-resistant epilepsy. At follow-up (mean ± SD, 5.4 ± 3.3 years), CRE patients with early surgery were more likely to have ILAE class 1 seizure freedom and AED independence than those with delayed surgery (92% (44/48) vs. 53% (8/15), p = 0.002; and 65% (31/48) vs. 33% (5/15), p = 0.03, respectively). Conclusions: Early CRE surgery demonstrated better seizure outcomes than delayed surgery. Multicenter prospective studies are needed to validate these findings. Full article

The duration of slow-wave sleep (SWS) is related to the reported sleep quality and to the important variables of mental and physical health. The internal cues to end an episode of SWS are poorly understood. One such internal cue is the initiation of a body movement, which is detectable as electromyographic (EMG) activity in sleep-electroencephalography (EEG). In the present study, we characterized the termination of SWS episodes by movement to explore its potential as a biomarker. To this end, we characterized the relation between the occurrence of SWS termination by movement and individual characteristics (age, sex), SWS duration and spectral content, chronotype, depression, medication, overnight memory performance, and, as a potential neurological application, epilepsy. We analyzed 94 full-night EEG-EMG recordings (75/94 had confirmed epilepsy) in the video-EEG monitoring unit of the EpiCARE Centre Salzburg, Austria. Segments of SWS were counted and rated for their termination by movement or not through the visual inspection of continuous EEG and EMG recordings. Multiple linear regression was used to predict the number of SWS episodes that ended with movement by depression, chronotype, type of epilepsy (focal, generalized, no epilepsy, unclear), medication, gender, total duration of SWS, occurrence of seizures during the night, occurrence of tonic-clonic seizures during the night, and SWS frequency spectra. Furthermore, we assessed whether SWS movement termination was related to overnight memory retention. According to multiple linear regression, patients with overall longer SWS experienced more SWS episodes that ended with movement (t = 5.64; p = 0.001). No other variable was related to the proportion of SWS that ended with movement, including no epilepsy-related variable. A small sample (n = 4) of patients taking Sertraline experienced no SWS that ended with movement, which was significant compared to all other patients (t = 8.00; p < 0.001) and to n = 35 patients who did not take any medication (t = 4.22; p < 0.001). While this result was based on a small subsample and must be interpreted with caution, it warrants replication in a larger sample with and without seizures to further elucidate the role of the movement termination of SWS and its potential to serve as a biomarker for sleep continuity and for medication effects on sleep. Full article

Once thought of as an immune-privileged site, we now know that the nervous system communicates in a bidirectional manner with the immune system via the neuroimmune axis. Neuropeptides constitute a component of this axis, playing critical roles in the brain and periphery. The function of salivary neuropeptides in the acute stress response is not well understood. The purpose of this study is to investigate salivary neuropeptide levels during acute stress. Salivary samples were collected from fire recruits engaged in a stress training exercise previously shown to induce acute stress, at three separate timepoints during the exercise and levels of oxytocin, neurotensin, Substance P, α-MSH, and β-Endorphin were measured using the Human Neuropeptide 5-Plex Custom Assay Eve Technologies. All neuropeptides increased throughout the acute stress simulation and during the recovery phase. Exploratory factor analysis (EFA) identified one factor contributing to baseline values across five neuropeptides and Pairwise Pearson Correlation Coefficient analysis showed positive correlations >0.9 for almost all neuropeptide combinations at the pre-stress timepoint. Further analysis identified negative and positive correlations between past-life trauma and self-assessed hardiness, respectively. Calculated neuropeptide scores showed an overall positive correlation to self-assessed hardiness. Altogether, our results suggest that salivary neuropeptides increase synchronously during acute stress and higher levels correlate with an increase in self-assessed hardiness. Further study is required to determine if interventions designed to enhance neuropeptide activity can increase stress resilience, especially in high-stress occupations such as firefighting. Full article

Executive functions (EFs) are related abilities, associated with the frontal lobes functions, that allow individuals to modify behavioral patterns when they become unsatisfactory. The aim of this study was to assess EFs in children with sensorineural hearing loss (SNHL) and in children with “specific language impairment” (SLI), compared with a control group of children with normal development, to identify specific skill deficits. Three groups of preschool children aged between 2 and 6 years were assessed: 19 children with normal hearing, cognitive, and language development, 10 children with SNHL, and 20 children with SLI. The FE-PS 2-6 Battery was used for the assessment of preschool EFs, supplemented with the Modified Bell Test for the analysis of selective attention. Statistically significant differences were found between the two experimental groups and the control one, regarding the investigated skills. Children with SNHL showed a clear deficit in flexibility, whereas children with SLI had greater problems in self-regulation and management of waiting for gratification. Selective attention was found to be deficient in all three groups, with no statistically significant differences. This study shows that the skills investigated were found to be deficient in both SNHL and SLI patients. It is essential to start targeted exercises based on specific deficient skills as part of the rehabilitation program. It is of great importance to understand the consequences of EF deficit in preschool children to achieve an accurate diagnosis and carry out customized rehabilitation programs. Full article

Background: In recent years, new technologies have been applied in cerebral palsy. Among these, immersive virtual reality is one with promising motor and cognitive effects along with the reduced costs of its application. The level of immersion of the subject in the illusional world gives the feeling of being a real part of the virtual environment. This study aims to investigate the safety and the efficacy of immersive virtual reality in children affected by cerebral palsy. Methods: PubMed, Embase, Cochrane Database of Systematic Reviews, RehabData, and Web of Science were screened up to February 2023 to identify eligible clinical studies. Results: Out of 788, we included 15 studies involving CP patients. There was high heterogeneity in the outcomes considered, and the results showed non-inferiority to conventional therapy and initial additional benefits in comparison with conventional rehabilitation. Conclusions: Immersive virtual reality emerges as a pivotal technological tool in rehabilitation, seamlessly integrating with conventional therapy within CP rehabilitation programs. Indeed, it not only enhances motivation but significantly increases children’s functional capacity and abilities. Full article

Background: Clinical case illustrations of patients with an impairment of personality functioning (IPF) have repeatedly reported that progress during psychotherapy is reflected by alterations in dream content. However, quantitative studies based on samples of psychotherapy patients are scarce. As a core component of both personality functioning and contemporary psychodynamic dream theory, the construct of affect regulation is of specific significance in this context. Aims: To test if improvement in personality functioning in the course of psychotherapy is associated with an increasing ability to regulate affects in dreams. Method: In a longitudinal design, affect regulation was compared in N = 94 unsolicited dream reports from the first vs. last third of long term psychotherapy of ten patients with initial IPF. Dream reports were transcribed from recordings of the sessions. Expert ratings of the level of personality functioning were obtained using the Scales of Psychological Capacities. The capacity for affect regulation was assessed using the Zurich Dream Process Coding System. Group differences were assessed using linear mixed models, controlling for dream length as well as the nested structure of this data set. Results: Patients demonstrated an increased capacity for affect regulation in dreams that was primarily evident in three core features: the complexity of dream elements (cf., e.g., parameter attributes, p = 0.024); the extent of affective involvement in the dream ego (cf., e.g., parameter subject feeling, p = 0.014); and the flexibility to regulate the dynamics of safety/involvement processes (p ≤ 0.001). This pattern was especially prominent in a subgroup (n = 7) of patients with more pronounced improvements in personality functioning. Conclusion: These findings support the hypotheses that decreasing IPF during psychotherapy is associated with increases in the capacity for affect regulation in dreams. Thus, researchers and therapists can utilize dream reports to illuminate the important aspects of treatment progress in clinical practice. Full article

(1) Background: The discovery of novel diagnostic methods and therapies for Alzheimer’s disease (AD) faces significant challenges. Previous research has shed light on the neuroprotective properties of Apelin-13 in neurodegenerative disorders. However, elucidating the mechanism underlying its efficacy in combating AD-related nerve injury is imperative. In this study, we aimed to investigate Apelin-13’s mechanism of action in an in vivo model of AD induced by streptozocin (STZ). (2) Methods: We utilized an STZ-induced nerve injury model of AD in mice to investigate the effects of Apelin-13 administration. Apelin-13 was administered intranasally, and cognitive impairment was assessed using standardized behavioral tests, primarily, behavioral assessment, histological analysis, and biochemical assays, in order to evaluate synaptic plasticity and oxidative stress signaling pathways. (3) Results: Our findings indicate that intranasal administration of Apelin-13 ameliorated cognitive impairment in the STZ-induced AD model. Furthermore, we observed that this effect was potentially mediated by the enhancement of synaptic plasticity and the attenuation of oxidative stress signaling pathways. (4) Conclusions: The results of this study suggest that intranasal administration of Apelin-13 holds promise as a therapeutic strategy for preventing neurodegenerative diseases such as AD. By improving synaptic plasticity and mitigating oxidative stress, Apelin-13 may offer a novel approach to neuroprotection in AD and related conditions. Full article

Exploring the spatiotemporal dynamic patterns of multi-channel electroencephalography (EEG) is crucial for interpreting dementia and related cognitive decline. Spatiotemporal patterns of EEG can be described through microstate analysis, which provides a discrete approximation of the continuous electric field patterns generated by the brain cortex. Here, we propose a novel microstate spatiotemporal dynamic indicator, termed the microstate sequence non-randomness index (MSNRI). The essence of the method lies in initially generating a sequence of microstate transition patterns through state space compression of EEG data using microstate analysis. Following this, we assess the non-randomness of these microstate patterns using information-based similarity analysis. The results suggest that this MSNRI metric is a potential marker for distinguishing between health control (HC) and frontotemporal dementia (FTD) (HC vs. FTD: 6.958 vs. 5.756, p < 0.01), as well as between HC and populations with Alzheimer’s disease (AD) (HC vs. AD: 6.958 vs. 5.462, p < 0.001). Healthy individuals exhibit more complex macroscopic structures and non-random spatiotemporal patterns of microstates, whereas dementia disorders lead to more random spatiotemporal patterns. Additionally, we extend the proposed method by integrating the Complementary Ensemble Empirical Mode Decomposition (CEEMD) method to explore spatiotemporal dynamic patterns of microstates at specific frequency scales. Moreover, we assessed the effectiveness of this innovative method in predicting cognitive scores. The results demonstrate that the incorporation of CEEMD-enhanced microstate dynamic indicators significantly improved the prediction accuracy of Mini-Mental State Examination (MMSE) scores (R² = 0.940). The CEEMD-enhanced MSNRI method not only aids in the exploration of large-scale neural changes in populations with dementia but also offers a robust tool for characterizing the dynamics of EEG microstate transitions and their impact on cognitive function. Full article

Background: The COVID-19 pandemic increased symptoms of stress and anxiety and induced changes in sleep quality, dream activity, and parasomnia episodes. It has been shown that stressful factors and/or bad sleep habits can affect parasomnia behaviors. However, investigations on how COVID-19 has affected sleep, dreams, and episode frequency in parasomnias are rare. The current study focuses on the impact of the pandemic on a specific parasomnia characterized by speech production (sleep talking, ST). Methods: We selected 27 participants with frequent ST episodes (STs) during the pandemic and compared them with 27 participants with frequent STs from a previous study conducted during a pre-pandemic period. All participants performed home monitoring through sleep logs and recorded their nocturnal STs for one week. Results: We observed a higher frequency of STs in the pandemic group. Moreover, STs were related to the emotional intensity of dreams, independent of the pandemic condition. The pandemic was associated with lower bizarreness of dreams in the pandemic group. There were no differences in sleep variables between the two groups. Conclusion: Overall, these results suggest a stressful effect of COVID-19 on the frequency of STs. Both the pandemic and the frequency of STs affect qualitative characteristics of dreams in this population. Full article

Background: Parents report associations between children’s sleep disturbances and behaviors. Children with neurodevelopmental conditions (e.g., Williams Syndrome and autism) are consistently reported to experience increased sleeping problems. Sleep in children with vision impairment and children with a dual diagnosis of vision impairment and autism remains understudied. Methods: Our exploratory study compared sleep profiles in 52 children (aged 4–12 years) and their parents (n = 37), across four groups: children with vision impairment (VI; n = 9), autism (n = 10), comorbid vision impairment + autism (n = 6), and typically developing children (n = 27). Childhood sleep was measured using the parental report Childhood Sleep Habits Questionnaire and sleep diaries. Children’s cognitive functioning was measured using digit span, semantic, and phonemic verbal fluency measures. Parental sleep was measured via the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Results: Clinically disordered sleep was reported in all child groups (p ≤ 0.001), particularly children with VI + autism. Age, not sleep quality/quantity, predicted cognitive task performance in TD and autistic groups, but not in VI and VI + autism groups. The child’s diagnosis affected parental sleep, particularly in children with a dual diagnosis of VI + autism. Conclusions: All participants experienced problematic sleep to varying degrees. Those most affected were children and parents in the VI + autism group, suggesting that autism may be the main driver of sleep problems in our sample. Full article

Recently, we and others have shown that manipulating the activity of cholinergic interneurons (CIN) present in the NAc can modulate binge alcohol consumption. The present study is designed to examine the relationship between binge alcohol consumption and the activity of the CIN in real time by using an in vivo microendoscopic technique. We hypothesized that mice exposed to Drinking in the Dark (DID)—a recognized mouse model for binge drinking—would exhibit increased activity in the accumbal shell region (NAcSh). To test this hypothesis, male mice expressing Cre-recombinase in the cholinergic neurons were exposed to binge alcohol consumption (alcohol group), employing the DID method, and utilized in vivo calcium imaging to observe CIN activity in real time during alcohol consumption. The control (sucrose) group was exposed to 10% (w/v) sucrose. As compared to sucrose, mice in the alcohol group displayed a significant increase in the frequency and amplitude of discharge activity, which was measured using calcium transients in the CIN present in the NAcSh. In summary, our findings suggest that the activity of CIN in the NAcSh plays a crucial role in alcohol self-administration. These results emphasize the potential significance of targeting CIN activity as a therapeutic approach for addressing AUD. Full article

Background: Despite the availability of pharmacotherapy and psychotherapy for treating obsessive–compulsive disorder (OCD), alternative approaches need to be explored due to the high likelihood of treatment resistance. Neuronavigated 20 Hz theta burst stimulation (TBS-20 Hz), targeting the bilateral dorsolateral prefrontal cortex (DLPFC) augmented with the right orbitofrontal cortex (ROFC), was tested for treating OCD comorbid with depression and anxiety disorders. Methods: A retrospective chart review was performed on fourteen patients treated for moderate-to-severe OCD in a private outpatient clinic. Twelve patients had comorbid major depressive disorder (MDD), and thirteen patients had either generalized anxiety disorder (GAD) or panic disorder (PD). Patients completed the Y-BOCS-SR, BDI-II, and BAI rating scales weekly, which were used to measure the changes in OCD, depression, and anxiety symptoms, respectively. Results: Neuronavigated TBS-20 Hz was sequentially applied to the right DLPFC (RDLPFC), left DLPFC (LDLPFC), and ROFC. A total of 64% (9/14) of patients achieved remission from OCD (Y-BOCS-SR ≤ 14) in an average of 6.1 weeks of treatment (SD = 4.0). A total of 58% (7/12) of patients remitted from MDD (BDI < 13) in an average of 4.1 weeks (SD = 2.8), and 62% (8/13) of patients remitted from GAD/PD (BAI < 8) in an average of 4.3 weeks (SD = 2.5). Conclusions: The neuronavigated TBS-20 Hz sequential stimulation of RDLPFC and LDLPFC, followed by ROFC, significantly reduced OCD, MDD, and GAD/PD symptoms. Randomized sham controls are warranted to validate these results. Full article

Objective: The aim of this study is to investigate the association between Cathepsin B and Parkinson’s Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. Methods: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. Results: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563–0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666–1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = −3.65% to 18.69%). Conclusions: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship. Full article

Hyperserotonemia is one of the most studied endophenotypes in autism spectrum disorder (ASD), but there are still no unequivocal results about its causes or biological and behavioral outcomes. This systematic review summarizes the studies investigating the relationship between blood serotonin (5-HT) levels and ASD, comparing diagnostic tools, analytical methods, and clinical outcomes. A literature search on peripheral 5-HT levels and ASD was conducted. In total, 1104 publications were screened, of which 113 entered the present systematic review. Of these, 59 articles reported hyperserotonemia in subjects with ASD, and 26 presented correlations between 5-HT levels and ASD-core clinical outcomes. The 5-HT levels are increased in about half, and correlations between hyperserotonemia and clinical outcomes are detected in a quarter of the studies. The present research highlights a large amount of heterogeneity in this field, ranging from the characterization of ASD and control groups to diagnostic and clinical assessments, from blood sampling procedures to analytical methods, allowing us to delineate critical topics for future studies. Full article

In patients with mild cognitive impairment (MCI), a lower level of cognitive function is associated with a higher likelihood of progression to dementia. In addition, gait disturbances and structural changes on brain MRI scans reflect cognitive levels. Therefore, we aimed to classify MCI based on cognitive level using gait parameters and brain MRI data. Eighty patients diagnosed with MCI from three dementia centres in Gangwon-do, Korea, were recruited for this study. We defined MCI as a Clinical Dementia Rating global score of ≥0.5, with a memory domain score of ≥0.5. Patients were classified as early-stage or late-stage MCI based on their mini-mental status examination (MMSE) z-scores. We trained a machine learning model using gait and MRI data parameters. The convolutional neural network (CNN) resulted in the best classifier performance in separating late-stage MCI from early-stage MCI; its performance was maximised when feature patterns that included multimodal features (GAIT + white matter dataset) were used. The single support time was the strongest predictor. Machine learning that incorporated gait and white matter parameters achieved the highest accuracy in distinguishing between late-stage MCI and early-stage MCI. Full article

The Michelangelo effect is a phenomenon that shows a reduction in perceived effort and an improvement in performance among both healthy subjects and patients when completing a motor task related to artistic stimuli, compared to performing the same task with non-artistic stimuli. It could contribute to the efficacy of art therapy in neurorehabilitation. In this study, the possible occurrence of this effect was tested in a cognitive task by asking 15 healthy subjects and 17 patients with a history of stroke to solve a digital version of the classical memory card game. Three different types of images were used in a randomized order: French cards, artistic portraits, and photos of famous people (to compensate for the possible effects of face recognition). Healthy subjects were involved to test the usability and the load demand of the developed system, reporting no statistically significant differences among the three sessions (p > 0.05). Conversely, patients had a better performance in terms of time (p = 0.014) and the number of attempts (p = 0.007) needed to complete the task in the presence of artistic stimuli, accompanied by a reduction in the perceived effort (p = 0.033). Furthermore, artistic stimuli, with respect to the other two types of images, seemed more associated with visuospatial control than linguistic functions. Full article

The generation of images from electroencephalography (EEG) signals has become a popular research topic in recent research because it can bridge the gap between brain signals and visual stimuli and has wide application prospects in neuroscience and computer vision. However, due to the high complexity of EEG signals, the reconstruction of visual stimuli through EEG signals continues to pose a challenge. In this work, we propose an EEG-ConDiffusion framework that involves three stages: feature extraction, fine-tuning of the pretrained model, and image generation. In the EEG-ConDiffusion framework, classification features of EEG signals are first obtained through the feature extraction block. Then, the classification features are taken as conditions to fine-tune the stable diffusion model in the image generation block to generate images with corresponding semantics. This framework combines EEG classification and image generation means to enhance the quality of generated images. Our proposed framework was tested on an EEG-based visual classification dataset. The performance of our framework is measured by classification accuracy, 50-way top-k accuracy, and inception score. The results indicate that the proposed EEG-Condiffusion framework can extract effective classification features and generate high-quality images from EEG signals to realize EEG-to-image conversion. Full article

The psychological refractory period (PRP) effect occurs when two stimuli that require separate responses are presented sequentially, particularly with a short and variable time interval between them. Fatigue is a suboptimal psycho-physiological state that leads to changes in strategies. In recent years, numerous studies have investigated the effects of transcranial direct current stimulation (tDCS) on motor control. The present study aimed to investigate the effects of two tDCS methods, anodal and cathodal, on PRP in ten different conditions of stimulus-onset asynchronies (SOAs) under non-fatigue and mental fatigue conditions. The participants involved 39 male university students aged 19 to 25 years. In the pre-test, they were assessed using the PRP measurement tool under both non-fatigue and mental fatigue conditions. The mental fatigue was induced by a 30-min Stroop task. The test consisted of two stimuli with different SOAs (50, 75, 100, 150, 300, 400, 600, 900, 1200, and 1500 ms). The first was a visual stimulus with three choices (letters A, B, and C). After a random SOA, the second stimulus, a visual stimulus with three choices (colors red, yellow, and blue), was presented. Subsequently, participants were randomly assigned to the anodal, cathodal, and sham stimulation groups and underwent four consecutive sessions of tDCS stimulation. In the anodal and cathodal stimulation groups, 20 min of tDCS stimulation were applied to the PLPFC area in each session, while in the sham group, the stimulation was artificially applied. All participants were assessed using the same measurement tools as in the pre-test phase, in a post-test phase one day after the last stimulation session, and in a follow-up phase four days after that. Inferential statistics include mixed ANOVA, one-way ANOVA, independent, and dependent t-tests. The findings indicated that the response time to the second stimulus was longer at lower SOAs. However, there was no significant difference between the groups in this regard. Additionally, there was no significant difference in response time to the second stimulus between the fatigue and non-fatigue conditions, or between the groups. Therefore, tDCS had no significant effect. There was a significant difference between mental fatigue and non-fatigue conditions in the psychological refractory period. Moreover, at lower SOAs, the PRP was longer than at higher SOAs. In conditions of fatigue, the active stimulation groups (anodal and cathodal) performed better than the sham stimulation group at higher SOAs. Considering the difference in response to both stimuli at different SOAs, some central aspects of the response can be simultaneously parallel. Fatigue also affects parallel processing. This study supports the response integration phenomenon in PRP, which predicts that there will be an increase in response time to the first stimulus as the interval between the presentation of the two stimuli increases. This finding contradicts the bottleneck model. In this study, the effectiveness of cathodal and anodal tDCS on response time to the second stimulus and PRP was found to be very small. Full article

Rotenone is a pesticide used in research for its ability to induce changes similar, in vivo and in vitro, to those observed in Parkinson’s disease (PD). This includes a selective death of dopaminergic neurons in the substantia nigra. Nonetheless, the precise mechanism through which rotenone modifies structure and function of neurons remains unclear. The PC12 cells closely resemble dopamine terminal neurons. This makes it a preferred model for studying the morphology of central dopamine neurons and predicting neurotoxicity. In this paper, we investigated the effects of 0.5 µM rotenone for 24–48 h on PC12 cell viability and ultrastructure (TEM), trying to identify primary and more evident alterations that can be related to neuronal damages similar to that seen in animal PD models. Cell viability decreased after 24 h rotenone treatment, with a further decrease after 48 h. Ultrastructural changes included vacuolar degeneration, mitochondrial mild swelling, decrease in the number of neuropeptide granules, and the loss of cell-to-cell adhesion. These findings are in agreement with previous research suggesting that rotenone, by inhibiting energy production and increasing ROS generation, is responsible for significant alterations of the ultrastructure and cell death of PC12 cells. Our data confirm the link between rotenone exposure, neuronal damage, and changes in dopamine metabolism, suggesting its role in the pathogenesis of PD. Full article

Infant attention is a cognitive function that underlines sensory–motor integration processes at the interface between the baby and the surrounding physical and socio-relational environment, mainly with the caregivers. The investigation of the role of non-visual inputs (i.e., vocal and tactile) provided by the caregivers in shaping infants’ attention in the context of visual impairment is relevant from both a theoretical and clinical point of view. This study investigated the social attention (i.e., gaze orientation) skills in a group of visually impaired (VI) and age-matched sighted controls (SCs) between 9 and 12 months of age. Moreover, the role of VI severity and maternal vocalizations and touch in shaping the social attention were investigated. Overall, 45 infants and their mothers participated in a video-recorded 4 min interaction procedure, including a play and a still-face episode. The infants’ gaze orientation (i.e., mother-directed, object-directed, or unfocused) and the types of maternal vocalizations and touch (i.e., socio-cognitive, affective) were micro-analytically coded. Maternal vocalizations and touch were found to influence gaze orientation differently in VI infants compared SCs. Moreover, the group comparisons during the play episode showed that controls were predominantly oriented to the mothers, while VI infants were less socially oriented. Visual impairment severity did not emerge as linked with social attention. These findings contribute to our understanding of socio-cognitive developmental trajectories in VI infants and highlight the need for tailored interventions to promote optimal outcomes for VI populations. Full article

Epilepsy is one of the most common neurological diseases. Epileptic seizures very often result in head injuries that may lead to many adverse consequences, both acute and chronic. They contribute to the need for hospitalization, modification of treatment, and a general decline in social productivity. The objective of our review is to characterize and assess management aspects of seizure-related head injuries (SRHIs) as an important and frequent clinical problem present in emergency department settings. PubMed and other relevant databases and websites were systematically searched for articles on traumatic brain injuries connected with the occurrence of seizures published from inception to 9 April 2024; then, we reviewed the available literature. Our review showed that SRHIs can lead to various acute complications, in some cases requiring hospitalization and neurosurgical intervention. Long-term complications and cognitive decline after injury might be present, eventually implying a negative impact on a patient’s quality of life. Despite being frequent and clinically important, there are still no widely accepted, uniform recommendations for the management of patients with SRHIs. As such, a concise and standardized protocol for the management of seizure-related head injuries in emergency departments is worth consideration. Full article

Differences in sensorimotor integration mechanisms have been observed between people who stutter (PWS) and controls who do not. Delayed auditory feedback (DAF) introduces timing discrepancies between perception and action, disrupting sequence production in verbal and non-verbal domains. While DAF consistently enhances speech fluency in PWS, its impact on non-verbal sensorimotor synchronization abilities remains unexplored. A total of 11 PWS and 13 matched controls completed five tasks: (1) unpaced tapping; (2) synchronization-continuation task (SCT) without auditory feedback; (3) SCT with DAF, with instruction either to align the sound in time with the metronome; or (4) to ignore the sound and align their physical tap to the metronome. Additionally, we measured participants’ sensitivity to detecting delayed feedback using a (5) delay discrimination task. Results showed that DAF significantly affected performance in controls as a function of delay duration, despite being irrelevant to the task. Conversely, PWS performance remained stable across delays. When auditory feedback was absent, no differences were found between PWS and controls. Moreover, PWS were less able to detect delays in speech and tapping tasks. These findings show subtle differences in non-verbal sensorimotor performance between PWS and controls, specifically when action–perception loops are disrupted by delays, contributing to models of sensorimotor integration in stuttering. Full article

Plastic production, which exceeds one million tons per year, is of global concern. The constituent low-density polymers enable spread over large distances and micro/nano particles (MNPLs) induce organ toxicity via digestion, inhalation, and skin contact. Particles have been documented in all human tissues including breast milk. MNPLs, especially weathered particles, can breach the blood–brain barrier, inducing neurotoxicity. This has been documented in non-human species, and in human-induced pluripotent stem cell lines. Within the brain, MNPLs initiate an inflammatory response with pro-inflammatory cytokine production, oxidative stress with generation of reactive oxygen species, and mitochondrial dysfunction. Glutamate and GABA neurotransmitter dysfunction also ensues with alteration of excitatory/inhibitory balance in favor of reduced inhibition and resultant neuro-excitation. Inflammation and cortical hyperexcitability are key abnormalities involved in the pathogenic cascade of amyotrophic lateral sclerosis (ALS) and are intricately related to the mislocalization and aggregation of TDP-43, a hallmark of ALS. Water and many foods contain MNPLs and in humans, ingestion is the main form of exposure. Digestion of plastics within the gut can alter their properties, rendering them more toxic, and they cause gut microbiome dysbiosis and a dysfunctional gut–brain axis. This is recognized as a trigger and/or aggravating factor for ALS. ALS is associated with a long (years or decades) preclinical period and neonates and infants are exposed to MNPLs through breast milk, milk substitutes, and toys. This endangers a time of intense neurogenesis and establishment of neuronal circuitry, setting the stage for development of neurodegeneration in later life. MNPL neurotoxicity should be considered as a yet unrecognized risk factor for ALS and related diseases. Full article

Virtual reality (VR) enables the development of virtual training frameworks suitable for various domains, especially when real-world conditions may be hazardous or impossible to replicate because of unique additional resources (e.g., equipment, infrastructure, people, locations). Although VR technology has significantly advanced in recent years, methods for evaluating immersion (i.e., the extent to which the user is engaged with the sensory information from the virtual environment or is invested in the intended task) continue to rely on self-reported questionnaires, which are often administered after using the virtual scenario. Having an objective method to measure immersion is particularly important when using VR for training, education, and applications that promote the development, fine-tuning, or maintenance of skills. The level of immersion may impact performance and the translation of knowledge and skills to the real-world. This is particularly important in tasks where motor skills are combined with complex decision making, such as surgical procedures. Efforts to better measure immersion have included the use of physiological measurements including heart rate and skin response, but so far they do not offer robust metrics that provide the sensitivity to discriminate different states (idle, easy, and hard), which is critical when using VR for training to determine how successful the training is in engaging the user’s senses and challenging their cognitive capabilities. In this study, electroencephalography (EEG) data were collected from 14 participants who completed VR jigsaw puzzles with two different levels of task difficulty. Machine learning was able to accurately classify the EEG data collected during three different states, obtaining accuracy rates of 86% and 97% for differentiating easy versus hard difficulty states and baseline vs. VR states. Building on these results may enable the identification of robust biomarkers of immersion in VR, enabling real-time recognition of the level of immersion that can be used to design more effective and translative VR-based training. This method has the potential to adjust aspects of VR related to task difficulty to ensure that participants are immersed in VR. Full article

Attention deficit hyperactivity disorder (ADHD) is a neuro-developmental disorder that affects approximately 5–10% of school-aged children worldwide. Early diagnosis and intervention are essential to improve the quality of life of patients and their families. In this study, we propose ConvMixer-ECA, a novel deep learning architecture that combines ConvMixer with efficient channel attention (ECA) blocks for the accurate diagnosis of ADHD using electroencephalogram (EEG) signals. The model was trained and evaluated using EEG recordings from 60 healthy children and 61 children with ADHD. A series of experiments were conducted to evaluate the performance of the ConvMixer-ECA. The results showed that the ConvMixer-ECA performed well in ADHD recognition with 94.52% accuracy. The incorporation of attentional mechanisms, in particular ECA, improved the performance of ConvMixer; it outperformed other attention-based variants. In addition, ConvMixer-ECA outperformed state-of-the-art deep learning models including EEGNet, CNN, RNN, LSTM, and GRU. t-SNE visualization of the output of this model layer validated the effectiveness of ConvMixer-ECA in capturing the underlying patterns and features that separate ADHD from typically developing individuals through hierarchical feature learning. These outcomes demonstrate the potential of ConvMixer-ECA as a valuable tool to assist clinicians in the early diagnosis and intervention of ADHD in children. Full article

We present a novel set of quantitative measures for “likeness” (error function) designed to alleviate the time-consuming and subjective nature of manually comparing biological recordings from electrophysiological experiments with the outcomes of their mathematical models. Our innovative “blended” system approach offers an objective, high-throughput, and computationally efficient method for comparing biological and mathematical models. This approach involves using voltage recordings of biological neurons to drive and train mathematical models, facilitating the derivation of the error function for further parameter optimization. Our calibration process incorporates measurements such as action potential (AP) frequency, voltage moving average, voltage envelopes, and the probability of post-synaptic channels. To assess the effectiveness of our method, we utilized the sea slug Melibe leonina swim central pattern generator (CPG) as our model circuit and conducted electrophysiological experiments with TTX to isolate CPG interneurons. During the comparison of biological recordings and mathematically simulated neurons, we performed a grid search of inhibitory and excitatory synapse conductance. Our findings indicate that a weighted sum of simple functions is essential for comprehensively capturing a neuron’s rhythmic activity. Overall, our study suggests that our blended system approach holds promise for enabling objective and high-throughput comparisons between biological and mathematical models, offering significant potential for advancing research in neural circuitry and related fields. Full article

B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain. C57BL/6j mice were intraperitoneally injected with a single dosage of lipopolysaccharide (LPS, 1 mg/kg) to induce inflammation. B355252 (1 mg/kg) intervention was started two days prior to the LPS injection. The animal behavioral changes were assessed pre- and post-LPS injections. The animal brains were harvested at 4 and 24 h post-LPS injection, and histological, biochemical, and cytokine array outcomes were examined. Results showed that B355252 improved LPS-induced behavioral deterioration, mitigated brain tissue damage, and suppressed the activation of microglial and astrocytes. Furthermore, B355252 reduced the protein levels of key pyroptotic markers TLR4, NLRP3, and caspase-1 and inhibited the LPS-induced increases in IL-1β, IL-18, and cytokines. In conclusion, B355252 demonstrates a potent anti-neuroinflammatory effect in vivo, suggesting that its potential therapeutic value warrants further investigation. Full article

The examination of connected speech may serve as a valuable tool for exploring speech output in both healthy speakers and individuals with language disorders. Numerous studies incorporate various fluency and silence measures into their analyses to investigate speech output patterns in different populations, along with the underlying cognitive processes that occur while speaking. However, methodological inconsistencies across existing studies pose challenges in comparing their results. In the current study, we introduce CSAP (Connected Speech Analysis Protocol), which is a specific methodological approach to investigate fluency metrics, such as articulation rate and speech rate, as well as silence measures, including silent pauses’ frequency and duration. We emphasize the importance of employing a comprehensive set of measures within a specific methodological framework to better understand speech output patterns. Additionally, we advocate for the use of distinct narrative tasks for a thorough investigation of speech output in different conditions. We provide an example of data on which we implement CSAP to showcase the proposed pipeline. In conclusion, CSAP offers a comprehensive framework for investigating speech output patterns, incorporating fluency metrics and silence measures in distinct narrative tasks, thus allowing a detailed quantification of connected speech in both healthy and clinical populations. We emphasize the significance of adopting a unified methodological approach in connected speech studies, enabling the integration of results for more robust and generalizable conclusions. Full article