Brain Sci., Volume 14, Issue 1 (January 2024) – 109 articles

Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives. Full article

Whereas traditional histology and light microscopy require multiple steps of formalin fixation, paraffin embedding, and sectioning to generate images for pathologic diagnosis, Microscopy using Ultraviolet Surface Excitation (MUSE) operates through UV excitation on the cut surface of tissue, generating images of high resolution without the need to fix or section tissue and allowing for potential use for downstream molecular tests. Here, we present the first study of the use and suitability of MUSE microscopy for neuropathological samples. MUSE images were generated from surgical biopsy samples of primary and metastatic brain tumor biopsy samples (n = 27), and blinded assessments of diagnoses, tumor grades, and cellular features were compared to corresponding hematoxylin and eosin (H&E) images. A set of MUSE-treated samples subsequently underwent exome and targeted sequencing, and quality metrics were compared to those from fresh frozen specimens. Diagnostic accuracy was relatively high, and DNA and RNA integrity appeared to be preserved for this cohort. This suggests that MUSE may be a reliable method of generating high-quality diagnostic-grade histologic images for neuropathology on a rapid and sample-sparing basis and for subsequent molecular analysis of DNA and RNA. Full article

It is still a matter of debate whether developmental prosopagnosia is a disorder selective to faces or whether object recognition is also affected. In a previous study, based on a small sample of developmental prosopagnosics (DPs; N = 10), we found impairments in both domains although the difficulties were most pronounced for faces. Importantly, impairments with faces and objects were systematically related. We suggested that that the seemingly disproportional impairment for faces in DP was likely to reflect differences between stimulus categories in visual similarity. Here, we aimed to replicate these findings in a larger, independent sample of DPs (N = 21) using the same experimental paradigms. Contrary to our previous results, we found no disproportional effect of visual similarity on performance with faces or objects in the new DP group when compared to controls (N = 21). The new DP group performed within the control range, and significantly better than the old DP-group, on sensitive and demanding object recognition tasks, and we can demonstrate a classical dissociation between face and object recognition at the group level. These findings are perhaps the strongest evidence yet presented for a face-specific deficit in developmental prosopagnosia. Full article

Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying mechanisms in insomnia treatment. We hypothesized that anodal prefrontal cortex stimulation activates glutamatergic projections from the infralimbic cortex (IL) to the ventrolateral preoptic area (VLPO) to promote sleep. After administering 0.06 mA of electrical currents for 8 min, our results indicate significant non-rapid eye movement (NREM) enhancement in naïve mice within the initial 3 h post-stimulation, persisting up to 16–24 h. In the insomnia group, tDCS enhanced NREM sleep bout numbers during acute stress response and improved NREM and REM sleep duration in subsequent acute insomnia. Sleep quality, assessed through NREM delta powers, remains unaffected. Interference of the IL-VLPO pathway, utilizing designer receptors exclusively activated by designer drugs (DREADDs) with the cre-DIO system, partially blocked tDCS’s sleep improvement in stress-induced insomnia. This study elucidated that the activation of the IL-VLPO pathway mediates tDCS’s effect on stress-induced insomnia. These findings support the understanding of tDCS effects on sleep disturbances, providing valuable insights for future research and clinical applications in sleep therapy. Full article

Individuals with internalizing conditions such as depression or anxiety are at risk of sleep difficulties. Social–ecological models of sleep health propose factors at the individual (e.g., mental health) and neighborhood (e.g., crime risk) levels that contribute to sleep difficulties. However, these relationships have been under-researched in terms of internalizing conditions. Therefore, the current study comprised participants diagnosed with major depression (n = 24) or social anxiety (n = 35). Sleep measures included actigraphic variables (i.e., total sleep time, waking after sleep onset, sleep onset latency) and subjective sleep quality. Geocoding was used to assess nationally-normed crime risk exposure at the person level (e.g., murder, assault) and property level (e.g., robbery, burglary). Analyses consisted of independent t-tests to evaluate potential differences between diagnostic groups. To examine relationships, multiple regressions were used with internalizing symptoms, crime risk, and age as independent variables and sleep measures as the dependent variable. The t-test results revealed that groups differed in symptoms and age but not sleep or neighborhood crime. Regression results revealed crime risk positively corresponded with sleep onset latency but no other sleep measures. Also, only depression positively corresponded with total sleep time. Preliminary findings suggest exposure to crime and depression relate differentially to facets of sleep in individuals with internalizing conditions. Full article

Single sided deafness (SSD) is characterized by significant sensorineural hearing loss, severe or profound, in only one ear. SSD adversely affects various aspects of auditory perception, including causing impairment in sound localization, difficulties with speech comprehension in noisy environments, and decreased spatial awareness, resulting in a significant decline in overall quality of life (QoL). Several treatment options are available for SSD, including cochlear implants (CI), contralateral routing of signal (CROS), and bone conduction devices (BCD). The lack of consensus on outcome domains and measurement tools complicates treatment comparisons and decision-making. This narrative overview aims to summarize the treatment options available for SSD in adult and pediatric populations, discussing their respective advantages and disadvantages. Rerouting devices (CROS and BCD) attenuate the effects of head shadow and improve sound awareness and signal-to-noise ratio in the affected ear; however, they cannot restore binaural hearing. CROS devices, being non-implantable, are the least invasive option. Cochlear implantation is the only strategy that can restore binaural hearing, delivering significant improvements in speech perception, spatial localization, tinnitus control, and overall QoL. Comprehensive preoperative counseling, including a discussion of alternative technologies, implications of no treatment, expectations, and auditory training, is critical to optimizing therapeutic outcomes. Full article

The current literature globally highlights the efficacy of Clozapine in several psychiatric disorders all over the world, with an FDA indication for reducing the risk of repeated suicidal behavior in patients with schizophrenia or schizoaffective disorder. A growing field of research is also stressing a possible broader beneficial effect of Clozapine in promoting neuroprotection and neurotrophism. However, this drug is linked to several life-threatening side effects, such as agranulocytosis, myocarditis and seizures, that limit its use in daily clinical practice. For this work, a search was performed on PubMed using the terms “Clozapine indications”, “Clozapine adverse effects”, “Clozapine regenerative effects”, and “Clozapine neuroplasticity” with the aim of reviewing the scientific literature on Clozapine’s treatment indications, adverse effects and potential regenerative role. The results confirmed the efficacy of clozapine in clinical practice, although limited by its adverse effects. It appears crucial to raise awareness among clinicians about the potential benefits of using Clozapine, as well educating medical personnel about its risks and the early identification of possible adverse effects and their management. Full article

Lithium remains an effective option in the treatment of bipolar disorder (BD). Thus, we aim to characterize the pharmaco-epidemiological patterns of lithium use internationally over time and elucidate clinical correlates associated with BD using a scoping review, which was conducted using the methodological framework by Arksey and O’Malley (2005). We searched several databases for studies that examined the prescriptions for lithium and clinical associations in BD from inception until December 2023. This review included 55 articles from 1967 to 2023, which collected data from North America (n = 24, 43.6%), Europe (n = 20, 36.4%), and Asia (n = 11, 20.0%). The overall prescription rates ranged from 3.3% to 84% (33.4% before and 30.6% after the median year cutoffs). Over time, there was a decline in lithium use in North America (27.7% before 2010 to 17.1% after 2010) and Europe (36.7% before 2003 to 35.7% after 2003), and a mild increase in Asia (25.0% before 2003 to 26.2% after 2003). Lithium use was associated with specific demographic (e.g., age, male gender) and clinical factors (e.g., lower suicide risk). Overall, we found a trend of declining lithium use internationally, particularly in the West. Specific clinical correlates can support clinical decision-making for continued lithium use. Full article

The dual-process theory of thought rests on the co-existence of two different thinking modalities: a quick, automatic, and associative process opposed to a slow, thoughtful, and deliberative process. The increasing interest in determining the neural foundation of the dual-process distinction has yielded mixed results, also given the difficulty of applying the fMRI standard approach to tasks usually employed in the cognitive literature. We report an activation likelihood estimation (ALE) meta-analysis to investigate the neural foundation of the dual-process theory of thought. Eligible studies allowed for the identification of cerebral areas associated with dual-process theory-based tasks without differentiating between fast and slow thinking. The ALE algorithm converged on the medial frontal cortex, superior frontal cortex, anterior cingulate cortex, insula, and left inferior frontal gyrus. These structures partially overlap with the cerebral areas recurrently reported in the literature about the neural basis of the dual-process distinction, where the PARCS theory-based interpretation emphasizes the role of the right inferior gyrus. The results confirm the potential (but still almost unexplored) common ground between the dual-process literature and the cognitive control literature. Full article

Parkinson’s disease (PD) is a multifactorial disease, with genetic and environmental factors contributing to the disease onset. Classically, PD is a movement disorder characterized by the loss of dopaminergic neurons in the nigrostriatal pathway and intraneuronal aggregates mainly constituted of the protein α-synuclein. However, PD patients also display non-motor symptoms, including depression, which have been linked to functional abnormalities of non-dopaminergic neurons, including serotonergic and noradrenergic ones. Thus, through this comprehensive literature review, we shed light on the noradrenergic and serotonergic impairment linked to depression in PD, focusing on the putative involvement of inflammatory mechanisms. Full article

Looming motion interacts with threatening emotional cues in the initial stages of visual processing. However, the underlying neural networks are unclear. The current study investigated if the interactive effect of threat elicited by angry and looming faces is favoured by rapid, magnocellular neural pathways and if exogenous or endogenous attention influences such processing. Here, EEG/ERP techniques were used to explore the early ERP responses to moving emotional faces filtered for high spatial frequencies (HSF) and low spatial frequencies (LSF). Experiment 1 applied a passive-viewing paradigm, presenting filtered angry and neutral faces in static, approaching, or receding motions on a depth-cued background. In the second experiment, broadband faces (BSF) were included, and endogenous attention was directed to the expression of faces. Our main results showed that regardless of attentional control, P1 was enhanced by BSF angry faces, but neither HSF nor LSF faces drove the effect of facial expressions. Such findings indicate that looming motion and threatening expressions are integrated rapidly at the P1 level but that this processing relies neither on LSF nor on HSF information in isolation. The N170 was enhanced for BSF angry faces regardless of attention but was enhanced for LSF angry faces during passive viewing. These results suggest the involvement of a neural pathway reliant on LSF information at the N170 level. Taken together with previous reports from the literature, this may indicate the involvement of multiple parallel neural pathways during early visual processing of approaching emotional faces. Full article

Sleep state misperception (SSM) is a common issue in insomnia disorder (ID), causing a discrepancy between objective and subjective sleep/wake time estimation and increased daytime impairments. In this context, the hyperarousal theory assumes that sustained central nervous system activation contributes to the SSM. This study investigates factors influencing SSM during sleep latency (SL) and total sleep time (TST). Objective polysomnographic sleep variables (the alpha density index, latency-to-sleep stages and the first K-complex, and Rapid Eye Movement (REM) arousal density) and subjective sleep indices, taken from sleep diaries, were analyzed in 16 ID patients. Correlation analyses revealed a positive association between the degree of SL misperception (SLm) and the percentage of epochs that contained a visually scored stereotyped alpha rhythm during objective SL. A regression analysis showed that the REM arousal density and alpha density index significantly predicted TST misperception (TSTm). Furthermore, the degree of SLm was associated with an increased probability of transitioning from stage 1 of non-REM sleep to wakefulness during subjective SL. These findings support the role of hyperarousal in SSM and highlight the importance of alpha activity in unravelling the heterogeneous underpinnings of SSM. Full article

There are approximately 24 million cases of Alzheimer’s disease (AD) worldwide, and the number of cases is expected to increase four-fold by 2050. AD is a neurodegenerative disease that leads to severe dementia in most patients. There are several neuropathological signs of AD, such as deposition of amyloid beta (Aβ) plaques, formation of neurofibrillary tangles (NFTs), neuronal loss, activation of inflammasomes, and declining autophagy. Several of these hallmarks are linked to the gut microbiome. The gastrointestinal (GI) tract contains microbial diversity, which is important in regulating several functions in the brain via the gut-brain axis (GBA). The disruption of the balance in the gut microbiota is known as gut dysbiosis. Recent studies strongly support that targeting gut dysbiosis with selective bioflavonoids is a highly plausible solution to attenuate activation of inflammasomes (contributing to neuroinflammation) and resume autophagy (a cellular mechanism for lysosomal degradation of the damaged components and recycling of building blocks) to stop AD pathogenesis. This review is focused on two bioflavonoids, specifically epigallocatechin-3-gallate (EGCG) and genistein (GS), as a possible new paradigm of treatment for maintaining healthy gut microbiota in AD due to their implications in modulating crucial AD signaling pathways. The combination of EGCG and GS has a higher potential than either agent alone to attenuate the signaling pathways implicated in AD pathogenesis. The effects of EGCG and GS on altering gut microbiota and GBA were also explored, along with conclusions from various delivery methods to increase the bioavailability of these bioflavonoids in the body. Full article

Tinnitus is a prevalent hearing-loss deficit manifested as a phantom (internally generated by the brain) sound that is heard as a high-frequency tone in the majority of afflicted persons. Chronic tinnitus is debilitating, leading to distress, sleep deprivation, anxiety, and even suicidal thoughts. It has been theorized that, in the majority of afflicted persons, tinnitus can be attributed to the loss of high-frequency input from the cochlea to the auditory cortex, known as deafferentation. Deafferentation due to hearing loss develops with aging, which progressively causes tonotopic regions coding for the lost high-frequency coding to synchronize, leading to a phantom high-frequency sound sensation. Approaches to tinnitus remediation that demonstrated promise include inhibitory drugs, the use of tinnitus-specific frequency notching to increase lateral inhibition to the deafferented neurons, and multisensory approaches (auditory–motor and audiovisual) that work by coupling multisensory stimulation to the deafferented neural populations. The goal of this review is to put forward a theoretical framework of a multisensory approach to remedy tinnitus. Our theoretical framework posits that due to vision’s modulatory (inhibitory, excitatory) influence on the auditory pathway, a prolonged engagement in audiovisual activity, especially during daily discourse, as opposed to auditory-only activity/discourse, can progressively reorganize deafferented neural populations, resulting in the reduced synchrony of the deafferented neurons and a reduction in tinnitus severity over time. Full article

Post-acute COVID-19 syndrome (PCS) is highly prevalent. Critically ill patients requiring intensive care unit (ICU) admission are at a higher risk of developing PCS. The mechanisms underlying PCS are still under investigation and may involve microvascular damage in the brain. Cerebral misery perfusion, characterized by reduced cerebral blood flow (CBF) and elevated oxygen extraction fraction (OEF) in affected brain areas, has been demonstrated in cerebrovascular diseases such as carotid occlusion and stroke. This pilot study aimed to examine whether COVID-19 ICU survivors exhibited regional misery perfusion, indicating cerebral microvascular damage. In total, 7 COVID-19 ICU survivors (4 female, 20–77 years old) and 19 age- and sex-matched healthy controls (12 female, 22–77 years old) were studied. The average interval between ICU admission and the MRI scan was 118.6 ± 30.3 days. The regional OEF was measured using a recently developed technique, accelerated T₂-relaxation-under-phase-contrast MRI, while the regional CBF was assessed using pseudo-continuous arterial spin labeling. COVID-19 ICU survivors exhibited elevated OEF (β = 5.21 ± 2.48%, p = 0.047) and reduced relative CBF (β = −0.083 ± 0.025, p = 0.003) in the frontal lobe compared to healthy controls. In conclusion, misery perfusion was observed in the frontal lobe of COVID-19 ICU survivors, suggesting microvascular damage in this critical brain area for high-level cognitive functions that are known to manifest deficits in PCS. Physiological biomarkers such as OEF and CBF may provide new tools to improve the understanding and treatment of PCS. Full article

Locked-in syndrome (LIS) is a rare and challenging condition that results in tetraplegia and cranial nerve paralysis while maintaining consciousness and variable cognitive function. Once acute management is completed, it is important to work with the patient on developing a plan to maintain and improve their quality of life (QOL). A key component towards increasing or maintaining QOL within this population involves the establishment of a functional communication system. Evaluating cognition in patients with LIS is vital for evaluating patients’ communication needs along with physical rehabilitation to maximize their QOL. In the past decade or so, there has been an increase in research surrounding brain–computer interfaces to improve communication abilities for paralyzed patients. This article provides an update on the available technology and the protocol for finding the best way for patients with this condition to communicate. This article aims to increase knowledge of how to enhance and manage communication among LIS patients. Full article

Aging often leads to awareness decline and psychological stress. Meditation, a method of modulating consciousness, may help individuals improve overall awareness and increase emotional resilience toward stress. This study explored the potential influence of the Awareness Training Program (ATP), a form of consciousness modulation, on age-related brain wave changes and psychological stress in middle-aged adults. Eighty-five participants with mild stress were recruited and randomly assigned to ATP (45.00 ± 8.00 yr) or control (46.67 ± 7.80 yr) groups, matched by age and gender. Ten-minute resting-state EEG data, obtained while the participants’ eyes were closed, were collected using a 128-channel EEG system (EGI). A strong positive Pearson correlation was found between fast-wave (beta wave, 12–25 Hz; gamma wave, 25–40 Hz) EEG and age. However, after the 7-week ATP intervention, this correlation became insignificant in the ATP group. Furthermore, there was a significant reduction in stress levels, as measured by the Chinese version of the 10 item Perceived Stress Scale (PSS-10), in the ATP group. These results suggest that ATP may help modulate age-related effects on fast brain waves, as evidenced by the reduced correlation magnitude between age and gamma waves, and lower psychological stress. This suggests that ATP, as a form of consciousness modulation, may improve stress resilience and modulate age-related gamma wave changes. Full article

Glioblastoma (GBM) is the most aggressive and treatment-resistant brain tumor. In the GBM microenvironment, interaction with microglia is associated with the dysregulation of cytokines, chemokines, and miRNAs, contributing to angiogenesis, proliferation, anti-apoptosis, and chemoresistance. The flavonoid rutin can inhibit glioma cell growth associated with microglial activation and production of pro-inflammatory mediators by mechanisms that are still poorly understood. The present study investigated the effect of rutin on viability, regulation of miRNA-125b, and the STAT3 expression in GBM cells, as well as the effects on the modulation of the inflammatory profile and STAT3 expression in microglia during indirect interaction with GBM cells. Human GL15-GBM cells and human C20 microglia were treated or not with rutin for 24 h. Rutin (30–50 μM) significantly reduced the viability of GL15 cells; however, it did not affect the viability of microglia. Rutin (30 μM) significantly reduced the expression of miRNA-125b in the cells and secretome and STAT3 expression. Microglia submitted to the conditioned medium from GBM cells treated with rutin showed reactive morphology associated with reduced expression of IL-6, TNF, and STAT3. These results reiterate the anti-glioma effects of the flavonoid, which may also modulate microglia towards a more responsive anti-tumor phenotype, constituting a promising molecule for adjuvant therapy to GBM. Full article

Glioblastoma is highly proliferative and invasive. However, the regulatory cytokine networks that promote glioblastoma cell proliferation and invasion into other areas of the brain are not fully defined. In the present study, we define a critical role for the IL-11/IL-11Rα signalling axis in glioblastoma proliferation, epithelial to mesenchymal transition, and invasion. We identified enhanced IL-11/IL-11Rα expression correlated with reduced overall survival in glioblastoma patients using TCGA datasets. Proteomic analysis of glioblastoma cell lines overexpressing IL-11Rα displayed a proteome that favoured enhanced proliferation and invasion. These cells also displayed greater proliferation and migration, while the knockdown of IL-11Rα reversed these tumourigenic characteristics. In addition, these IL-11Rα overexpressing cells displayed enhanced invasion in transwell invasion assays and in 3D spheroid invasion assays, while knockdown of IL-11Rα resulted in reduced invasion. Furthermore, IL-11Rα-overexpressing cells displayed a more mesenchymal-like phenotype compared to parental cells and expressed greater levels of the mesenchymal marker Vimentin. Overall, our study identified that the IL-11/IL-11Rα pathway promotes glioblastoma cell proliferation, EMT, and invasion. Full article

Calcium and iron are essential elements that regulate many important processes of eukaryotic cells. Failure to maintain homeostasis of calcium and iron causes cell dysfunction or even death. PD (Parkinson’s disease) is the second most common neurological disorder in humans, for which there are currently no viable treatment options or effective strategies to cure and delay progression. Pathological hallmarks of PD, such as dopaminergic neuronal death and intracellular α-synuclein deposition, are closely involved in perturbations of iron and calcium homeostasis and accumulation. Here, we summarize the mechanisms by which Ca²⁺ signaling influences or promotes PD progression and the main mechanisms involved in ferroptosis in Parkinson’s disease. Understanding the mechanisms by which calcium and iron imbalances contribute to the progression of this disease is critical to developing effective treatments to combat this devastating neurological disorder. Full article

Cranial electrotherapy stimulation (CES) delivers low-intensity electrical currents to the brain to treat anxiety, depression, and pain. Though CES is considered safe and cost-effective, little is known about side effects emerging across different contexts. Our objective was to investigate how varying physical and cognitive demands impact the frequency and intensity of CES vestibular sensations in a sample of healthy young adults. We used a 2 (stimulation: sham, active) × 2 (physical demand: static sway, dynamic sit-to-stand) × 2 (cognitive demand: single-task remain silent, dual-task count backward) repeated measures design. Vestibular sensations were measured with surveys and wearable sensors capturing balance changes. Active stimulation did not influence reported vestibular sensations. Instead, high physical demand predicted more sensation reports. High cognitive demand, but not active stimulation, predicted postural sway unsteadiness. Significant effects of active stimulation on balance were observed only during the dynamic sit-to-stand transitions. In summary, CES induces vestibular sensations only for a specific outcome under certain circumstances. Our findings imply that consumers can safely maximize the benefits of CES while ensuring they are taking steps to minimize any potential side effects by considering their context and circumstances. Full article

The predictive coding theory is currently widely accepted as the theoretical basis of perception and chronic perceptual disorders are explained as the maladaptive compensation of the brain to a prediction error. Although this gives us a general framework to work with, it is still not clear who may be more susceptible and/or vulnerable to aberrations in this system. In this paper, we study changes in predictive coding through the lens of tinnitus and pain. We take a step back to understand how the predictive coding system develops from infancy, what are the different neural and bio markers that characterise this system in the acute, transition and chronic phases and what may be the factors that pose a risk to the aberration of this system. Through this paper, we aim to identify people who may be at a higher risk of developing chronic perceptual disorders as a reflection of aberrant predictive coding, thereby giving future studies more facets to incorporate in their investigation of early markers of tinnitus, pain and other disorders of predictive coding. We therefore view this paper to encourage the thinking behind the development of preclinical biomarkers to maladaptive predictive coding. Full article

Migraine is a burdensome neurological disorder that still lacks clear and easily accessible diagnostic biomarkers. Furthermore, a straightforward pathway is hard to find for migraineurs’ management, so the search for response predictors has become urgent. Nowadays, artificial intelligence (AI) has pervaded almost every aspect of our lives, and medicine has not been missed. Its applications are nearly limitless, and the ability to use machine learning approaches has given researchers a chance to give huge amounts of data new insights. When it comes to migraine, AI may play a fundamental role, helping clinicians and patients in many ways. For example, AI-based models can increase diagnostic accuracy, especially for non-headache specialists, and may help in correctly classifying the different groups of patients. Moreover, AI models analysing brain imaging studies reveal promising results in identifying disease biomarkers. Regarding migraine management, AI applications showed value in identifying outcome measures, the best treatment choices, and therapy response prediction. In the present review, the authors introduce the various and most recent clinical applications of AI regarding migraine. Full article

Children and adolescents with externalizing problems show physiological hypo-reactivity toward affective stimuli, which may relate to their disruptive, antisocial, and thrill-seeking behaviors. This study examines differences in explicit and implicit emotion regulation between preadolescents with and without externalizing problems as well as the role of emotion regulation in subjective and autonomic responses to emotional stimuli. Preadolescents showing self- and other-reported externalizing psychopathology, and a control sample, without such difficulties, participated in a passive affective picture-viewing task with neutral, fearful, joyful, and sad images, while their heart rate and heart rate variability were measured. Participants also reported on their emotion regulation difficulties using the Difficulties in Emotion Regulation Scale. Compared to controls, youths scoring high on externalizing problems (1) reported greater emotion regulation difficulties, especially a lack of emotional clarity and difficulty in controlling impulsive actions, (2) showed higher resting heart rate variability and a lower resting heart rate, suggestive of higher emotion/autonomic regulation ability, and (3) showed both subjective and physiological hypo-arousal to emotional pictures. Heart rate variability and, to a lesser degree difficulties in emotional clarity, modulated the effects of emotional pictures on subjective and physiological arousal. Findings suggest that interventions to improve emotion regulation and awareness may help to prevent externalizing problems. Full article

This paper proposes the “calm contact” technique: an imaginative scenario where someone is in gentle contact with a loved one where the essence of the experience is to enjoy safety and calmness in peaceful social contact. The theoretical background is outlined by combining the brain mechanisms of stress reactions and hypnosis. In addition to the ancient stress responses (flight or fight or freeze), there are oxytocin-based options at the human level: tend and befriend behavior and the state of calm and connection, which is not a stress reaction but a resting reaction. These social-based reactions could prevent the organism from the primitive freezing response. Some studies proved that “hypnosis” as a setting reduces cortisol levels and could raise oxytocin levels. The beneficial mechanisms of the “calm contact” technique are analyzed in relation to “social support” and the psychoaffective effects of central oxytocin. The subjective effects of the proposed technique are outlined based on reports of healthy volunteers. The “calm contact” technique could be an alternative or adjunct to the “safe place” technique, applying the recent findings of endocrinological brain mechanisms of hypnosis. Clinical implications and limitations are briefly summarized. Full article

Glioblastoma (GBM) is a primary malignant tumor of the central nervous system responsible for the most deaths among patients with primary brain tumors. Current therapies for GBM are not effective, with the average survival of GBM patients after diagnosis being limited to a few months. Chemotherapy is difficult in this case due to the heterogeneity of GBM and the high efficacy of the blood–brain barrier, which makes drug absorption into the brain extremely difficult. In a previous study, 3′,4′,3,4,5-trimethoxychalcone (MB) showed antiproliferative and anti-invasion activities toward GBM cells. Polymersomes (PMs) are an attractive, new type of nanoparticle for drug administration, due to their high stability, enhanced circulation time, biodegradability, and sustained drug release. In the present study, different MB formulations, PEG2000-PCL and PEG5000-PCL, were synthesized, characterized, and compared in terms of 14-day stability and in vitro cytotoxicity (hCMEC/D3 and U-373 MG). Full article

Maintaining standing balance is essential for people to engage in productive activities in daily life. However, the process of interaction between the cortex and the muscles during balance regulation is understudied. Four balance paradigms of different difficulty were designed by closing eyes and laying sponge pad under feet. Ten healthy subjects were recruited to stand for ten 15 s trials in each paradigm. This study used simultaneously acquired electroencephalography (EEG) and electromyography (EMG) to investigate changes in the human cortico-muscular coupling relationship and functional brain network characteristics during balance control. The coherence and causality of EEG and EMG signals were calculated by magnitude-squared coherence (MSC) and transfer entropy (TE). It was found that changes in balance strategies may lead to a shift in cortico-muscular coherence (CMC) from the beta band to the gamma band when the difficulty of balance increased. As subjects performed the four standing balance paradigms, the causality of the beta band and the gamma band was stronger in the descending neural pathway than that in the ascending neural pathway. A multi-rhythmic functional brain network with 19 EEG channels was constructed and analyzed based on graph theory, showing that its topology also changed with changes in balance difficulty. These results show an active adjustment of the sensorimotor system under different balance paradigms and provide new insights into the endogenous physiological mechanisms underlying the control of standing balance. Full article

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary of various scales and patient-reported outcome measures (PROMs) used in stroke research and their MCID values reported in the literature, including a concise overview of the concept of and methods for determining MCIDs in stroke research. Despite the controversies and limitations surrounding the estimation of MCIDs, their importance in modern clinical trials cannot be overstated. Anchor-based and distribution-based methods are recommended for estimating MCIDs, with patient self-evaluation being a crucial component in capturing the patient’s perspective on their health. A combination of methods can provide a more comprehensive understanding of the clinical relevance of treatment effects, and incorporating the patient’s perspective can enhance the care of stroke patients. Full article