Editor’s Choice Articles

Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are critical neurological conditions that necessitate specialized care in the Intensive Care Unit (ICU). Managing cerebral perfusion pressure (CPP) and mean arterial pressure (MAP) is of primary importance in these patients. To maintain targeted MAP and CPP, vasopressors and/or inotropes are commonly used. However, their effects on cerebral oxygenation are not fully understood. The aim of this review is to provide an up-to date review regarding the current uses and pathophysiological issues related to the use of vasopressors and inotropes in TBI and SAH patients. According to our findings, despite achieving similar hemodynamic parameters and CPP, the effects of various vasopressors and inotropes on cerebral oxygenation, local CBF and metabolism are heterogeneous. Therefore, a more accurate understanding of the cerebral activity of these medications is crucial for optimizing patient management in the ICU setting. Full article

Accumulating evidence from behavioral studies and neuroscience suggests that motor and cognitive development are intrinsically intertwined. To explore the underlying mechanisms of this motor–cognition link, our study examined the longitudinal relationship of early motor skills and physical activity with later cognitive skills. The sample was 3188 children from the United Kingdom Millennium Cohort Study, followed at 9 months and 5, 7, and 11 years. Early motor skills were examined at 9 months. Children’s daily physical activity level was measured using accelerometers at 7 years and a questionnaire was conducted at 11 years. Cognitive skills, including executive function and academic achievement, were measured at age 11. The results suggest that gross motor skills were positively associated with spatial working memory, whereas fine motor skills were predictive of good English and science outcomes. Moderate-to-vigorous activity was found to be negatively associated with English performance, although self-reported activity frequency was positively linked to math. Our results highlight the significant role of both gross and fine motor skills in cognitive development. This study also elucidates the limitations of using activity intensity to assess the impact of motor activity on children’s cognitive development, suggesting that attention to the effects of specific types of physical activity would better elucidate the motor/cognition link. Full article

Rett syndrome (RTT) is a neurological disorder that mostly affects females, with a frequency of 1 in 10,000 to 20,000 live birth cases. Symptoms include stereotyped hand movements; impaired learning, language, and communication skills; sudden loss of speech; reduced lifespan; retarded growth; disturbance of sleep and breathing; seizures; autism; and gait apraxia. Pneumonia is the most common cause of death for patients with Rett syndrome, with a survival rate of 77.8% at 25 years of age. Survival into the fifth decade is typical in Rett syndrome, and the leading cause of death is cardiorespiratory compromise. Rett syndrome progression has multiple stages; however, most phenotypes are associated with the nervous system and brain. In total, 95% of Rett syndrome cases are due to mutations in the MECP2 gene, an X-linked gene that encodes for the methyl CpG binding protein, a regulator of gene expression. In this review, we summarize the recent developments in the field of Rett syndrome and therapeutics targeting MECP2. Full article

Assessing executive functions in individuals with disorders or clinical conditions can be challenging, as they may lack the abilities needed for conventional test formats. The use of more personalized test versions, such as adaptive assessments, might be helpful in evaluating individuals with specific needs. This paper introduces PsycAssist, a web-based artificial intelligence system designed for neuropsychological adaptive assessment and training. PsycAssist is a highly flexible and scalable system based on procedural knowledge space theory and may be used potentially with many types of tests. We present the architecture and adaptive assessment engine of PsycAssist and the two currently available tests: Adap-ToL, an adaptive version of the Tower of London-like test to assess planning skills, and MatriKS, a Raven-like test to evaluate fluid intelligence. Finally, we describe the results of an investigation of the usability of Adap-ToL and MatriKS: the evaluators perceived these tools as appropriate and well-suited for their intended purposes, and the test-takers perceived the assessment as a positive experience. To sum up, PsycAssist represents an innovative and promising tool to tailor evaluation and training to the specific characteristics of the individual, useful for clinical practice. Full article

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

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

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

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

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

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 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

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

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

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

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

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

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

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

Background: Previous investigations on healthy humans showed conflicting evidence regarding the impact of mood on working memory performance. A systematic investigation of how mood affects apathy levels in healthy participants is currently missing. Methods: We administered a visuospatial (VS) and a numerical (N) n-back task to a sample of 120 healthy individuals. In these participants, using a series of questionnaires, we also evaluated apathy, mood, working memory, perceived stress, PTSD symptoms caused by the COVID-19 pandemic outbreak, and general psychiatric symptoms. Successively, we investigated their performance in the n-back task as a function of scores to these questionnaires. Results: Participants performed better in the N block than in the VS one. Their accuracy decreased as a function of the n-back difficulty. We reported no differences in working memory performance or apathy as a function of mood, stress, or PTSD symptoms. We found that phobic anxiety negatively predicted accuracy to the numerical n-back task and that subjects with greater anxiety and difficulty in regulating emotions also showed higher levels of withdrawal from the task. Conclusion: The study’s results suggest that while mood did not significantly affect working memory performance, strong associations were found between WMQ scores and working memory capabilities. Full article

Neuralgic amyotrophy, also called Parsonage–Turner syndrome, in its classic presentation is a brachial plexopathy or a multifocal neuropathy, involving mainly motor nerves of the upper limb with a monophasic course. Recently, a new radiological entity was described, the hourglass constriction, which is characterized by a very focal constriction of a nerve, or part of it, usually associated with nerve thickening proximally and distally to the constriction. Another condition, which is similar from a radiological point of view to hourglass constriction, is nerve torsion. The pathophysiology of neuralgic amyotrophy, hourglass constriction and nerve torsion is still poorly understood, and a generic role of inflammation is proposed for all these conditions. It is now widely accepted that nerve imaging is necessary in identifying hourglass constrictions/nerve torsion pre-surgically in patients with an acute mononeuropathy/plexopathy. Ultrasound and MRI are useful tools for diagnosis, and they are consistent with intraoperative findings. The prognosis is generally favorable after surgery, with a high rate of good motor recovery. Full article

Epilepsy represents a condition in which abnormal neuronal discharges or the hyperexcitability of neurons occur with synchronicity, presenting a significant public health challenge. Prognostic factors, such as etiology, electroencephalogram (EEG) abnormalities, the type and number of seizures before treatment, as well as the initial unsatisfactory effects of medications, are important considerations. Although there are several third-generation antiepileptic drugs currently available, their multiple side effects can negatively affect patient quality of life. The inheritance and etiology of epilepsy are complex, involving multiple underlying genetic and epigenetic mechanisms. Different neurotransmitters play crucial roles in maintaining the normal physiology of different neurons. Dysregulations in neurotransmission, due to abnormal transmitter levels or changes in their receptors, can result in seizures. In this review, we address the roles played by various neurotransmitters and their receptors in the pathophysiology of epilepsy. Furthermore, we extensively explore the neurological mechanisms involved in the development and progression of epilepsy, along with its risk factors. Furthermore, we highlight the new therapeutic targets, along with pharmacological and non-pharmacological strategies currently employed in the treatment of epileptic syndromes, including drug interventions employed in clinical trials related to epilepsy. Full article

Background: Dynamic technological development and its enormous impact on modern societies are posing new challenges for 21st-century neuroscience. A special place is occupied by technologies based on virtual reality (VR). VR tools have already played a significant role in both basic and clinical neuroscience due to their high accuracy, sensitivity and specificity and, above all, high ecological value. Objective: Being in a digital world affects the functioning of the body as a whole and its individual systems. The data obtained so far, both from experimental and modeling studies, as well as (clinical) observations, indicate their great and promising potential, but apart from the benefits, there are also losses and negative consequences for users. Methods: This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework across electronic databases (such as Web of Science Core Collection; PubMed; and Scopus, Taylor & Francis Online and Wiley Online Library) to identify beneficial effects and applications, as well as adverse impacts, especially on brain health in human neuroscience. Results: More than half of these articles were published within the last five years and represent state-of-the-art approaches and results (e.g., 54.7% in Web of Sciences and 63.4% in PubMed), with review papers accounting for approximately 16%. The results show that in addition to proposed novel devices and systems, various methods or procedures for testing, validation and standardization are presented (about 1% of articles). Also included are virtual developers and experts, (bio)(neuro)informatics specialists, neuroscientists and medical professionals. Conclusions: VR environments allow for expanding the field of research on perception and cognitive and motor imagery, both in healthy and patient populations. In this context, research on neuroplasticity phenomena, including mirror neuron networks and the effects of applied virtual (mirror) tasks and training, is of interest in virtual prevention and neurogeriatrics, especially in neurotherapy and neurorehabilitation in basic/clinical and digital neuroscience. Full article

A precise neuropsychological assessment is of the utmost importance for neurosurgical patients undergoing the surgical excision of cerebral lesions. The assessment of mathematical abilities is usually limited to arithmetical operations while other fundamental visuo-spatial aspects closely linked to mathematics proficiency, such as the perception of numerical quantities and geometrical reasoning, are completely neglected. We evaluated these abilities with two objective and reproducible psychophysical tests, measuring numerosity perception and non-symbolic geometry, respectively. We tested sixteen neuro-oncological patients before the operation and six after the operation with classical neuropsychological tests and with two psychophysical tests. The scores of the classical neuropsychological tests were very heterogeneous, possibly due to the distinct location and histology of the tumors that might have spared (or not) brain areas subserving these abilities or allowed for plastic reorganization. Performance in the two non-symbolic tests reflected, on average, the presumed functional role of the lesioned areas, with participants with parietal and frontal lesions performing worse on these tests than patients with occipital and temporal lesions. Single-case analyses not only revealed some interesting exceptions to the group-level results (e.g., patients with parietal lesions performing well in the numerosity test), but also indicated that performance in the two tests was independent of non-verbal reasoning and visuo-spatial working memory. Our results highlight the importance of assessing non-symbolic numerical and geometrical abilities to complement typical neuropsychological batteries. However, they also suggest an avoidance of reliance on an excessively rigid localizationist approach when evaluating the neuropsychological profile of oncological patients. Full article

Executive functions are related to the control of cognition, emotion, and behavior. They are essential to lifelong outcomes, including school performance. Naturalistic interventions embedded in children’s daily activities and environments have greater effects. Therefore, this pilot study aimed to develop a naturalistic program suitable for schools, based on Goal Management Training (GMT), and to analyze its effects on executive functions and behavior. The participants consisted of 35 students from 2nd to 5th grade with executive dysfunction complaints. They underwent neuropsychological assessments of working memory, inhibition, cognitive flexibility, and intellectual capacity. Teachers and parents answered questionnaires on executive functions and behavior. Students were randomly assigned to an active control group, who participated in sessions on citizenship, and an experimental group (EG), stimulated through the executive function program, both with 16 sessions conducted by psychologists. After the intervention, all participants were reevaluated. The two-way Wald-type statistic (WTS) revealed greater improvement in executive functions for the EG, including working memory and inhibition. Additionally, parents and teachers, blind to the experimental conditions, reported improvements in some measures of executive functions and behavior. The results are encouraging, but further studies should test the intervention when implemented with larger samples and by teachers. Full article

Due to similar manifestations, some authors have proposed a potential correlation between autism spectrum disorder (ASD) and obsessive–compulsive disorder (OCD). This link has long been recognized and debated, with some authors arguing that these disorders frequently occur comorbid but distinct while others believe they are part of the same spectrum. The aim of our study was to explore the prevalence and correlates of autistic traits in 55 OCD patients and 55 matched controls and to assess possible autistic dimensions predictive of higher OCD symptoms. All participants were assessed with the Obsessive–Compulsive Spectrum-Short Version (OBS-SV) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). The OCD group scored significantly higher in both questionnaires. Total OBS-SV scores and domains were significantly correlated with all AdAS Spectrum domains and total score. The AdAS Spectrum total, Verbal Communication and Inflexibility and adherence to routine domain scores were significant positive predictors of higher OBS-SV scores. Lastly, when two clusters of subjects (high and low autism) were determined, Inflexibility and adherence to routine domain presented the greatest influence in forming the clusters. Our findings support the association between OCD and autistic traits in the adult population, supporting the hypothesis of a neurodevelopmental basis for these psychiatric conditions. Full article

Motor memories can be strengthened through online practice and offline consolidation. Offline consolidation involves the stabilization of memory traces in post-practice periods. Following initial consolidation of a motor memory, subsequent practice of the motor skill can lead to reactivation and reconsolidation of the memory trace. The length of motor memory reactivation may influence motor learning outcomes; for example, brief, as opposed to long, practice of a previously learned motor skill appears to optimize intermanual transfer in healthy young adults. However, the influence of aging on reactivation-based motor learning has been scarcely explored. Here, the effects of brief and long motor memory reactivation schedules on the retention and intermanual transfer of a visuomotor tracing task are explored in healthy older adults. Forty older adults practiced a virtual star-tracing task either three (“brief reactivation”) or ten (“long reactivation”) times per session over a two-week period. Comparison with a previously reported group of younger adults revealed significant age-related differences in the effect of the motor memory reactivation schedule on the intermanual transfer of the motor task. In older adults, unlike younger adults, no significant between-group differences were found by practice condition in the speed, accuracy, or skill of intermanual task transfer. That is, motor task transfer in healthy younger, but not older, adults appears to benefit from brief memory reactivation. These results support the use of age-specific motor training approaches and may inform motor practice scheduling, with possible implications for physical rehabilitation, sport, and music. Full article

(1) Background: Transcranial direct current stimulation (tDCS) appears to alleviate chronic pain via a brain-down mechanism. Although several review studies have examined the effects of tDCS on patients with chronic pain, no systematic review or meta-analysis has comprehensively analyzed the effects of tDCS on chronic orthopedic joint pain in one study. We aim to evaluate the effectiveness of tDCS for pain reduction in chronic orthopedic patients; (2) Methods: A comprehensive search of five electronic databases (Medline, Embase, Web of Science, CINAHL, and Cochrane) was performed. Only randomized controlled trials that compared tDCS with a control intervention were included. Eighteen studies met our inclusion criteria. We identified four categories of chronic orthopedic pain: knee (k = 8), lower back (k = 7), shoulder (k = 2), and orofacial pain (k = 1). Random effect models were utilized, and a sensitivity analysis was conducted in the presence of significant heterogeneity. Studies within each pain condition were further classified according to the number of treatment sessions: 1–5 sessions, 6–10 sessions, and >10 sessions.; (3) Results: Significant reductions in chronic orthopedic joint pain were observed following tDCS compared to controls for knee (g = 0.59, p = 0.005), lower back (g = 1.14, p = 0.005), and shoulder (g = 1.17, p = 0.020). Subgroup analyses showed pain reductions after 6–10 tDCS sessions for knee pain and after 1–5 and >10 sessions for lower back pain; (4) Conclusions: tDCS could be considered a potential stand-alone or supplemental therapy for chronic knee and lower back pain. The effectiveness of tDCS treatment varies depending on the number of treatment sessions. Our findings suggest the importance of implementing individualized treatment plans when considering tDCS for chronic pain conditions. Full article

Divergent thinking (DT) is widely considered an essential cognitive dimension of creativity, which involves goal-oriented processes, including working memory (WM), which allows for retrieving and loading of information into the attentional stream and, consequently, enhancing divergence of thinking. Despite the critical role of WM in DT, little work has been done on the mechanism affecting this interplay. The current study addressed the involvement of a formal musical background in the relationship between WM and DT and was conducted with 83 healthy young adults (M = 19.64 years; SD = 0.52 years; 33 females). The participants were requested to indicate if they had a formal background in music in the conservatory (M = 4.78 years; SD = 5.50 years) as well as perform the digit span forward test (DSFT) and the alternative uses task—AUT from the Torrance test of creative thinking (TTCT). The results indicated that years of formal musical background moderated the association between WM and DT. These findings suggest that music enhances the positive effect of high-order cognitive processes, such as WM, on the ability to think divergently. Theoretical and practical implications as well as limitations were discussed. Full article

Due to the widespread involvement of distributed collaboration triggered by COVID-19, it has become a new trend that has continued into the post-pandemic era. This study investigated collective performance within two collaborative environments (co-located and distancing settings) by assessing inter-brain synchrony patterns (IBS) among design collaborators using functional near-infrared spectroscopy. The preliminary study was conducted with three dyads who possessed 2–3 years of professional product design experience. Each dyad completed two designated design tasks in distinct settings. In the distributed condition, participants interacted through video conferencing in which they were allowed to communicate by verbalization and sketching using a shared digital whiteboard. To prevent the influences of different sketching tools on design outputs, we employed digital sketching for both environments. The interactions between collaborators were identified in three behaviors: verbal only, sketch only, and mixed communication (verbal and sketch). The consequences revealed a higher level of IBS when mixed communication took place in distributed conditions than in co-located conditions. Comparably, the occurrence of IBS increased when participants solely utilized sketching as the interaction approach within the co-located setting. A mixed communication method combining verbalization and sketching might lead to more coordinated cognitive processes when in physical isolation. Design collaborators are inclined to adjust their interaction behaviors in order to adapt to different design environments, strengthen the exchange of ideas, and construct design consensus. Overall, the present paper discussed the performance of virtual collaborative design based on a neurocognitive perspective, contributing valuable insights for the future intervention design that promotes effective virtual teamwork. Full article

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed toward examining post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and Trisomy 21 (T21, Down syndrome). This N-of-1 randomized trial examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) over 10 sessions of anodal tDCS (1.5 mA, 25 cm) over Broca’s area with the cathode over the contralateral region was compared to 10 sessions of sham-tDCS and four control sessions in a 20-year-old male individual with T21 presenting moderate–severe childhood apraxia of speech (CAS). The accuracy for NSW production progressively improved (gain of 40%) under tDCS (sham-tDCS and control sessions showed < 20% gain). A decrease in speech severity from moderate–severe to mild–moderate indicated transfer effects in speech production. Speech accuracy under tDCS was correlated with Wernicke’s area activation (P3 current source density), which in turn was correlated with the activation of the left supramarginal gyrus and the Sylvian parietal–temporal junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated speech sound acquisition in a young adult with T21 and CAS, possibly through activating brain regions required for phonological working memory. Full article

In this narrative review, we delve into the evolving concept of brain health, as recognized by the WHO, focusing on its intersection with cognitive decline. We emphasize the imperative need for preventive strategies, particularly in older adults. We describe the target population that might benefit the most from risk-based approaches—namely, people with subjective cognitive decline. Additionally, we consider universal prevention in cognitively unimpaired middle-aged and older adults. Delving into multidomain personalized preventive strategies, we report on empirical evidence surrounding modifiable risk factors and interventions crucial in mitigating cognitive decline. Next, we highlight the emergence of brain health services (BHS). We explain their proposed role in risk assessment, risk communication, and tailored interventions to reduce the risk of dementia. Commenting on ongoing BHS pilot experiences, we present the inception and framework of our own BHS in Monza, Italy, outlining its operational structure and care pathways. We emphasize the need for global collaboration and intensified research efforts to address the intricate determinants of brain health and their potential impact on healthcare systems worldwide. Full article

Resistance training induces neuromuscular adaptations and its impact on spasticity remains inadequately researched. This systematic review (PROSPERO: CRD42022322164) aimed to analyze the effects of resistance training, compared with no treatment, conventional therapy, or other therapies, in people with stroke-related spasticity. A comprehensive search was conducted up to October 2023 in PubMed, PEDro, Cochrane, Web of Science, and Scopus databases. Selection criteria were randomized controlled trials involving participants with stroke-related spasticity intervened with resistance training. The PEDro scale was used to evaluate the methodological quality. From a total of 274 articles, 23 full-text articles were assessed for eligibility and nine articles were included in the systematic review, involving 225 participants (155 males, 70 females; mean age: 59.4 years). Benefits were found to spasticity after resistance training. Furthermore, studies measuring spasticity also reported benefits to function, strength, gait, and balance. In conclusion, resistance training was superior to, or at least equal to, conventional therapy, other therapies, or no intervention for improving spasticity, as well as function, strength, gait, and balance. However, the results should be taken with caution because of the heterogeneity of the protocols used. Further research is needed to explore the effects of resistance training programs on people with stroke. Full article

Traumatic brain injury (TBI) is a pervasive public health crisis that severely impacts the quality of life of affected individuals. Like peripheral forms of trauma, TBI results from extraordinarily heterogeneous environmental forces being imparted on the cranial space, resulting in heterogeneous disease pathologies. This has made therapies for TBI notoriously difficult to develop, and currently, there are no FDA-approved pharmacotherapies specifically for the acute or chronic treatment of TBI. TBI is associated with changes in cognition and can precipitate the onset of debilitating psychiatric disorders like major depressive disorder (MDD), generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Complicating these effects of TBI, FDA-approved pharmacotherapies utilized to treat these disorders often fail to reach the desired level of efficacy in the context of neurotrauma. Although a complicated association, decades of work have linked central serotonin (5-HT) neurotransmission as being involved in the etiology of a myriad of neuropsychiatric disorders, including MDD and GAD. 5-HT is a biogenic monoamine neurotransmitter that is highly conserved across scales of biology. Though the majority of 5-HT is isolated to peripheral sites such as the gastrointestinal (GI) tract, 5-HT neurotransmission within the CNS exerts exquisite control over diverse biological functions, including sleep, appetite and respiration, while simultaneously establishing normal mood, perception, and attention. Although several key studies have begun to elucidate how various forms of neurotrauma impact central 5-HT neurotransmission, a full determination of precisely how TBI disrupts the highly regulated dynamics of 5-HT neuron function and/or 5-HT neurotransmission has yet to be conceptually or experimentally resolved. The purpose of the current review is, therefore, to integrate the disparate bodies of 5-HT and TBI research and synthesize insight into how new combinatorial research regarding 5-HT neurotransmission and TBI may offer an informed perspective into the nature of TBI-induced neuropsychiatric complications. Full article

Several studies have shown that emotions are asymmetrically represented in the human brain and have proposed three main models (the ‘right hemisphere hypothesis’, the ‘approach-withdrawal hypothesis’ and the ‘valence hypothesis’) that give different accounts of this emotional laterality. Furthermore, in recent years, many investigations have suggested that a similar emotional laterality may also exist in different animal taxa. However, results of a previous systematic review of emotional laterality in non-human primates have shown that some of these studies might be criticized from the methodological point of view and support only in part the hypothesis of a continuum in emotional laterality across vertebrates. The aim of the present review therefore consisted in trying to expand this survey to other cognitively developed and highly social mammals, focusing attention on mainly visual aspects of emotional laterality, in studies conducted on the animal categories of horses, elephants, dolphins and whales. The 35 studies included in the review took into account three aspects of mainly visual emotional laterality, namely: (a) visual asymmetries for positive/familiar vs. negative/novel stimuli; (b) lateral position preference in mother–offspring or other affiliative interactions; (c) lateral position preference in antagonistic interactions. In agreement with data obtained from human studies that have evaluated comprehension or expression of emotions at the facial or vocal level, these results suggest that a general but graded right-hemisphere prevalence in the processing of emotions can be found at the visual level in cognitively developed non-primate social mammals. Some methodological problems and some implications of these results for human psychopathology are briefly discussed. Full article

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical–cortical interactions in arousal, few have explored the relationship between subcortical–cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression. Full article

Interleukin 6 (IL-6) receptor inhibitors tocilizumab and sarilumab have recently been approved for severe coronavirus disease 2019 (COVID-19). They also affect mood, even though their effect on the post-COVID-19 syndrome-related psychopathology still has to be investigated. The aim of this study was to investigate their effect on psychopathology in a sample of patients with post-COVID-19 syndrome. We included 246 patients (34% female, 66% male) aged 18–75 years who had been hospitalized for COVID. Patients were split into those who received anti-IL-6 receptor agents (Anti-IL-6-R, N = 88) and those who did not (Ctrl, N = 158). The former group was further split into those receiving tocilizumab (TOC, N = 67) and those receiving sarilumab (SAR, N = 21). Groups were compared based on clinical characteristics before and during COVID-19 as well as on physical and psychiatric symptoms after COVID-19. Ctrl had less psychiatric and physical symptoms during hospitalization and more post-COVID-19 diarrhea, headache, cough, and dyspnea upon exertion than those receiving IL-6-receptor inhibitors. Ctrl also showed greater difficulties in emotion regulation. These differences were driven by TOC vs. Ctrl, whereas differences between SAR and Ctrl or TOC did not reach significance. IL-6 receptor inhibitors are related to a lower post-COVID-19 illness burden and seem to be effective in emotion regulation. Further research is needed to confirm these findings. Full article

A new postmodern depression type, named “Modern-Type Depression” (MTD), is emerging in Western countries. MTD is often underdiagnosed, mainly due to potentially higher comorbidity with technology-based addictions, including Internet Gaming Disorder (IGD). However, the definition of the relationship between MTD and IGD is still controversial, as few data have been published thus far. In particular, there are no data specifically investigating the prevalence of MTD within Italian young subjects with IGD, as well as their mutual association. Hence, within the SWATCH (Social Withdrawal and TeCno-mediated mental Health issues) project, our study aimed to identify the prevalence of MTD in a sample of Italian young adults who play video games by providing a clinical characterization of MTD within a group of IGD individuals (IGD+) versus a group without IGD (IGD−) who play video games. Our cross-sectional case–control study recruited a sample of 543 Italian young video-gaming players (aged 18–35) from the larger SWATCH database, stratified as IGD+ versus IGD−. Subjects were administered the 22-item Tarumi’s Modern-Type Depression Trait Scale (TACS-22), the Motives for Online Gaming Questionnaire (MOGQ), and the Internet Gaming Disorder Scale-Short Form (IGDS9-SF). Around 21.7% of the total sample was represented by MTD individuals, while within the IGD sample, around 34% of subjects had MTD. Within the MTD group, significantly higher scores at IGDS-9SF (p < 0.001), MOGQ “Escape from reality” (p < 0.001), “Fantasy” (p < 0.001), and MOGQ total score (p = 0.003) were found compared to MTD−. According to the multivariate regression model, controlled for sex and age, higher scores in the TACS-22 were positively predicted by the total score of IGDS9-SF (p = 0.003), the MOGQ “Escape from Reality” subscale (p = 0.014), and MOGQ “Fantasy” (p = 0.011), and negatively predicted by the MOGQ “Competition” subscale (p = 0.035) [F (4538) = 17.265; p < 0.001]. Our findings suggested that MTD displays a strong association with IGD. Video-gaming players who do not have IGD appear to be less prone to MTD; this suggests that further studies could be carried out to specifically investigate whether pathological use of video games could also be determined by the presence of MTD. Full article

Alzheimer’s disease (AD), as the main cause of dementia, affects millions of people around the world, whose diagnosis is based mainly on clinical criteria. Unfortunately, the diagnosis is obtained very late, when the neurodegenerative damage is significant for most patients. Therefore, the exhaustive study of biomarkers is indispensable for diagnostic, prognostic, and even follow-up support. AD is a multifactorial disease, and knowing its underlying pathological mechanisms is crucial to propose new and valuable biomarkers. In this review, we summarize some of the main biomarkers described in AD, which have been evaluated mainly by imaging studies in cerebrospinal fluid and blood samples. Furthermore, we describe and propose neuronal precursors derived from the olfactory neuroepithelium as a potential resource to evaluate some of the widely known biomarkers of AD and to gear toward searching for new biomarkers. These neuronal lineage cells, which can be obtained directly from patients through a non-invasive and outpatient procedure, display several characteristics that validate them as a surrogate model to study the central nervous system, allowing the analysis of AD pathophysiological processes. Moreover, the ease of obtaining and harvesting endows them as an accessible and powerful resource to evaluate biomarkers in clinical practice. Full article

Low-Grade Gliomas (LGGs) represent a diverse group of brain tumors originating from glial cells, characterized by their unique histopathological and molecular features. This article offers a comprehensive exploration of LGGs, shedding light on their subtypes, histological and molecular aspects. By delving into the World Health Organization’s grading system, 5th edition, various specificities were added due to an in-depth understanding of emerging laboratory techniques, especially genomic analysis. Moreover, treatment modalities are extensively discussed. The degree of surgical resection should always be considered according to postoperative quality of life and cognitive status. Adjuvant therapies focused on chemotherapy and radiotherapy depend on tumor grading and invasiveness. In the current literature, emerging targeted molecular therapies are well discussed due to their succinctly therapeutic effect; in our article, those therapies are summarized based on posttreatment results and possible adverse effects. This review serves as a valuable resource for clinicians, researchers, and medical professionals aiming to deepen their knowledge on LGGs and enhance patient care. Full article

This systematic review assesses current molecular targeted therapies for glioblastoma multiforme (GBM), a challenging condition with limited treatment options. Using PRISMA methodology, 166 eligible studies, involving 2526 patients (61.49% male, 38.51% female, with a male-to-female ratio of 1.59/1), were analyzed. In laboratory studies, 52.52% primarily used human glioblastoma cell cultures (HCC), and 43.17% employed animal samples (mainly mice). Clinical participants ranged from 18 to 100 years, with 60.2% using combined therapies and 39.8% monotherapies. Mechanistic categories included Protein Kinase Phosphorylation (41.6%), Cell Cycle-Related Mechanisms (18.1%), Microenvironmental Targets (19.9%), Immunological Targets (4.2%), and Other Mechanisms (16.3%). Key molecular targets included Epidermal Growth Factor Receptor (EGFR) (10.8%), Mammalian Target of Rapamycin (mTOR) (7.2%), Vascular Endothelial Growth Factor (VEGF) (6.6%), and Mitogen-Activated Protein Kinase (MEK) (5.4%). This review provides a comprehensive assessment of molecular therapies for GBM, highlighting their varied efficacy in clinical and laboratory settings, ultimately impacting overall and progression-free survival in GBM management. Full article

Glioblastoma multiforme (GBM) is a primary malignant brain tumor characterized by a high grade of malignancy and an extremely unfavorable prognosis. The current efficacy of established treatments for GBM is insufficient, necessitating the prompt development of novel therapeutic approaches. The progress made in the fundamental scientific understanding of GBM is swiftly translated into more advanced stages of therapeutic studies. Despite extensive efforts to identify new therapeutic approaches, GBM exhibits a high mortality rate. The current efficacy of treatments for GBM patients is insufficient due to factors such as tumor heterogeneity, the blood–brain barrier, glioma stem cells, drug efflux pumps, and DNA damage repair mechanisms. Considering this, pharmacological cocktail therapy has demonstrated a growing efficacy in addressing these challenges. Towards this, various forms of immunotherapy, including the immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy have emerged as potential strategies for enhancing the prognosis of GBM. Current investigations are focused on exploring combination therapies to mitigate undesirable side effects and enhance immune responses against tumors. Furthermore, clinical trials are underway to evaluate the efficacy of several strategies to circumvent the blood–brain barrier (BBB) to achieve targeted delivery in patients suffering from recurrent GBM. In this review, we have described the biological and molecular targets for GBM therapy, pharmacologic therapy status, prominent resistance mechanisms, and new treatment approaches. We also discuss these promising therapeutic approaches to assess prospective innovative therapeutic agents and evaluated the present state of preclinical and clinical studies in GBM treatment. Overall, this review attempts to provide comprehensive information on the current status of GBM therapy. Full article

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide and others) now promises effective, non-invasive treatment of obesity for individuals with and without diabetes. Social media platforms’ users started promoting semaglutide/Ozempic as a weight-loss treatment, and the associated increase in demand has contributed to an ongoing worldwide shortage of the drug associated with levels of non-prescribed semaglutide intake. Furthermore, recent reports emphasized some GLP-1 RA-associated risks of triggering depression and suicidal thoughts. Consistent with the above, we aimed to assess the possible impact of GLP-1 RAs on mental health as being perceived and discussed in popular open platforms with the help of a mixed-methods approach. Reddit posts yielded 12,136 comments, YouTube videos 14,515, and TikTok videos 17,059, respectively. Out of these posts/entries, most represented matches related to sleep-related issues, including insomnia (n = 620 matches); anxiety (n = 353); depression (n = 204); and mental health issues in general (n = 165). After the initiation of GLP-1 RAs, losing weight was associated with either a marked improvement or, in some cases, a deterioration, in mood; increase/decrease in anxiety/insomnia; and better control of a range of addictive behaviors. The challenges of accessing these medications were a hot topic as well. To the best of our knowledge, this is the first study documenting if and how GLP-1 RAs are perceived as affecting mood, mental health, and behaviors. Establishing a clear cause-and-effect link between metabolic diseases, depression and medications is difficult because of their possible reciprocal relationship, shared underlying mechanisms and individual differences. Further research is needed to better understand the safety profile of these molecules and their putative impact on behavioral and non-behavioral addictions. Full article

Studies have demonstrated that many regions in the human brain include multidirectional fiber tracts, in which the diffusion of water molecules within image voxels does not follow a Gaussian distribution. Therefore, the conventional diffusion tensor imaging (DTI) that hypothesizes a single fiber orientation within a voxel is intrinsically incapable of revealing the complex microstructures of brain tissues. Diffusion spectrum imaging (DSI) employs a pulse sequence with different b-values along multiple gradient directions to sample the diffusion information of water molecules in the entire q-space and then quantitatively estimates the diffusion profile using a probability density function with a high angular resolution. Studies have suggested that DSI can reliably observe the multidirectional fibers within each voxel and allow fiber tracking along different directions, which can improve fiber reconstruction reflecting the true but complicated brain structures that were not observed in the previous DTI studies. Moreover, with increasing angular resolution, DSI is able to reveal new neuroimaging biomarkers used for disease diagnosis and the prediction of disorder progression. However, so far, this method has not been used widely in clinical studies, due to its overly long scanning time and difficult post-processing. Within this context, the current paper aims to conduct a comprehensive review of DSI research, including the fundamental principles, methodology, and application progress of DSI tractography. By summarizing the DSI studies in recent years, we propose potential solutions towards the existing problem in the methodology and applications of DSI technology as follows: (1) using compressed sensing to undersample data and to reconstruct the diffusion signal may be an efficient and promising method for reducing scanning time; (2) the probability density function includes more information than the orientation distribution function, and it should be extended in application studies; and (3) large-sample study is encouraged to confirm the reliability and reproducibility of findings in clinical diseases. These findings may help deepen the understanding of the DSI method and promote its development in clinical applications. Full article

Reelin is an extracellular matrix glycoprotein involved in neuronal migration during embryonic brain development and synaptic plasticity in the adult brain. The role of Reelin in the developing central nervous system has been extensively characterized. Indeed, a loss of Reelin or a disruption in its signaling cascade leads to neurodevelopmental defects and is associated with ataxia, intellectual disability, autism, and several psychiatric disorders. In the adult brain, Reelin is critically involved in neurogenesis and synaptic plasticity. Reelin’s signaling potentiates glutamatergic and GABAergic neurotransmission, induces synaptic maturation, and increases AMPA and NMDA receptor subunits’ expression and activity. As a result, there is a growing literature reporting that a loss of function and/or reduction of Reelin is implicated in numerous neurodegenerative diseases. The present review summarizes the current state of the literature regarding the implication of Reelin and Reelin-mediated signaling during aging and neurodegenerative disorders, highlighting Reelin as a possible target in the prevention or treatment of progressive neurodegeneration. Full article

β-carotene is a powerful antioxidant and dietary precursor of vitamin A whose role in maintaining mental health and cognitive performance, either alone or in combination with other dietary compounds, has been a topic of recent research. However, its effectiveness is still unclear. This systematic review, conducted according to the PRISMA guideline and assisted by the MySLR platform, addressed this issue. A total of 16 eligible original research articles were identified. Dietary intake or β-carotene serum levels were associated with improved measures of cognitive function in 7 out of 10 epidemiological studies included. In intervention studies, β-carotene consumption alone did not promote better cognitive function in the short term, but only in a long-term intervention with a mean duration of 18 years. However, all but one intervention study suggested the beneficial effects of β-carotene supplementation at doses ranging from 6 mg to 50 mg per day in combination with a multicomplex such as vitamin E, vitamin C, zinc, or selenium for a period of 16 weeks to 20 years. Despite the current limitations, the available evidence suggests a potential association between β-carotene dietary/supplementary intake and the maintenance of cognitive function. The β-carotene most probably does not act alone but in synergy with other micronutrients. Full article

Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence on the drugs approved for SMA allowed a significant acceleration in the experimental phase of these drugs. However, since these drugs had been authorized through accelerated programs, the conduction of post-marketing studies was requested as a condition of their marketing approval to better understand their risk–benefit profiles in real-world settings. As of the 4 January 2023, a total of 69 post-marketing studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). Currently, ongoing studies are primarily aimed at providing evidence concerning the risk–benefit profile of the three drugs in specific populations that were not included in the pivotal trials and to investigate the long-term safety and clinical benefits of these drugs. Real-world data sources collecting information regarding the natural history of the disease and post-marketing surveillance of the available therapies are increasingly becoming essential for generating real-world evidence on this rare disease and its orphan drugs. Full article

Social cognition involves skills for maintaining harmonious personal and social relationships throughout life. Social cognition issues, including Theory of Mind (ToM), can significantly impact the well-being of older individuals and intensify with the onset of neurological conditions. Mild Cognitive Impairment (MCI) is a state between healthy and pathological neurocognitive aging, where monitoring social functions is crucial. Despite numerous studies on ToM challenges in older adults and cognitive disorders, the underlying mechanisms remain debated. Uncertainty exists regarding whether ToM deficits are related to other cognitive functions, such as Executive Functions (EFs). Our study examined the correlation between EF and ToM performance in 32 MCI patients and 36 healthy elderly controls. The findings revealed a link between EF and ToM performance among healthy elderly individuals. Specifically, within the assessed EFs, the role of the working memory (WM) emerged. The study also highlighted distinctions between the MCI group and the healthy elderly group, showing that despite a general reduction in cognitive performance, the condition could impact these abilities in different ways. The study contributes to the literature, fostering comprehension of the mechanisms underlying ToM difficulties, while also paving the way for targeted interventions and enhanced clinical or preventative care. Full article

The independent detection and classification of brain malignancies using magnetic resonance imaging (MRI) can present challenges and the potential for error due to the intricate nature and time-consuming process involved. The complexity of the brain tumor identification process primarily stems from the need for a comprehensive evaluation spanning multiple modules. The advancement of deep learning (DL) has facilitated the emergence of automated medical image processing and diagnostics solutions, thereby offering a potential resolution to this issue. Convolutional neural networks (CNNs) represent a prominent methodology in visual learning and image categorization. The present study introduces a novel methodology integrating image enhancement techniques, specifically, Gaussian-blur-based sharpening and Adaptive Histogram Equalization using CLAHE, with the proposed model. This approach aims to effectively classify different categories of brain tumors, including glioma, meningioma, and pituitary tumor, as well as cases without tumors. The algorithm underwent comprehensive testing using benchmarked data from the published literature, and the results were compared with pre-trained models, including VGG16, ResNet50, VGG19, InceptionV3, and MobileNetV2. The experimental findings of the proposed method demonstrated a noteworthy classification accuracy of 97.84%, a precision success rate of 97.85%, a recall rate of 97.85%, and an F1-score of 97.90%. The results presented in this study showcase the exceptional accuracy of the proposed methodology in accurately classifying the most commonly occurring brain tumor types. The technique exhibited commendable generalization properties, rendering it a valuable asset in medicine for aiding physicians in making precise and proficient brain diagnoses. Full article

Background: Sport-related concussion (SRC) is a common sport injury. Females are participating in sports at increasing rates, and there is growing awareness that female athletes may be more vulnerable to SRC. Objectives: We aimed to identify sex differences in epidemiology, clinical manifestation and assessment of SRC and examine how these relate to the 6th International Conference on Concussion in Sport (ICCS). Methods: We conducted a scoping review of the Medline database and identified 58 studies examining the effects of sex on SRC in collegiate and high school athletes that were written in English and published in a peer-reviewed journal between March 2012 and March 2022. Results: We found that female athletes suffer higher rates of concussion in sex-comparable sports, in particular soccer. Female athletes experience more somatic symptoms—headache/migraine/sleep disturbance—and may take longer to recover from concussion. Sex differences were also identified regarding some aspects of sideline concussion assessment with the Sport Concussion Assessment Tool. Conclusions: Females are at greater risk and experience SRC differently than males; this is mostly likely due to a combination of biomechanical factors, differences in neck musculature and hormonal and social factors. Sex differences are not widely addressed by the 6th ICSS, which informs many sports’ concussion protocols. Full article