Brain Sci., Volume 13, Issue 10 (October 2023) – 146 articles

Autoimmune neuromuscular diseases are a group of heterogenous pathologies secondary to the activation of the immune system that damage the structures of the peripheric nerve, the neuromuscular junction, or the skeleton muscle. The diagnosis of autoimmune neuromuscular disorders comprises a combination of data from clinical, laboratory, electromyography, imaging exam, and biopsy. Particularly, the whole-body MRI examination in the last two decades has been of great use in the assessment of neuromuscular disorders. MRI provides information about the structures involved and the status of activity of the disease. It can also be used as a biomarker, detect the pattern of specific muscle involvement, and is a useful tool for targeting the optimal muscle site for biopsy. In this work, we summarized the most used technical protocol of whole-body MRI and the role of this imaging technique in autoimmune neuromuscular disorders. Full article

(1) Objective: Narcissism is characterized by emotional regulation deficits, a lack of empathy for others, and extreme self-focus. Narcissism has also been linked to an increased desire for fame and celebrity worship. Here, the neuroscience underlying narcissism is examined in order to determine what regions and networks of the brain are altered when non-narcissistic individuals are compared to participants with both grandiose and vulnerable narcissism. (2) Methods: The behavioral relationships between grandiose narcissism and desire for fame and vulnerable narcissism and celebrity worship are explored, along with a possible relationship at the neural level between these constructs. In this paper, we review research demonstrating that increased levels of grandiose narcissism are associated with an increase in obsession with fame, while vulnerable narcissism is associated with celebrity worship. (3) Results: Based on current data, the frontal regions underlie narcissism and also likely underlie celebrity worship and desire for fame. This tenuous conclusion is based on a limited number of studies. (4) Conclusions: The brain areas associated with grandiose narcissism may be associated with an intense desire for fame as well, while brain regions associated with vulnerable narcissism may be similar in celebrity worshipers. Future research studies on the brain that are specifically designed to test these relationships at a neurological level are needed. Full article

Frailty is an emerging concept in clinical practice used to predict outcomes and dictate treatment algorithms. Frail patients, especially older adults, are at higher risk for adverse outcomes. Aneurysmal subarachnoid hemorrhage (aSAH) is a neurosurgical emergency associated with high morbidity and mortality rates that have previously been shown to correlate with frailty. However, the relationship between treatment selection and post-treatment outcomes in frail aSAH patients is not established. We conducted a meta-analysis of the relevant literature in accordance with PRISMA guidelines. We searched PubMed, Embase, Web of Science, and Google Scholar using “Subarachnoid hemorrhage AND frailty” and “subarachnoid hemorrhage AND frail” as search terms. Data on cohort age, frailty measurements, clinical grading systems, and post-treatment outcomes were extracted. Of 74 studies identified, four studies were included, with a total of 64,668 patients. Percent frailty was 30.4% under a random-effects model in all aSAH patients (p < 0.001). Overall mortality rate of aSAH patients was 11.7% when using a random-effects model (p < 0.001). There was no significant difference in mortality rate between frail and non-frail aSAH patients, but this analysis only included two studies and should be interpreted cautiously. Age and clinical grading, rather than frailty, independently predicted outcomes and mortality in aSAH patients. 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

Tinnitus (the perception of sound in the absence of any corresponding external source) is highly prevalent and can be distressing. There are unanswered questions about how tinnitus, suicidal thoughts, and suicidal behaviours co-occur and interact. To establish the extent of scientific literature, this scoping review catalogued primary reports addressing the associations between tinnitus, suicidal ideation, attempted suicide, and death by suicide. We searched OvidSP, Medline, EMBASE, PsycINFO, CINAHL, Google Scholar, EThoS, and ProQuest for all studies and case reports on ideation and/or attempted and/or completed suicide in the context of tinnitus. Twenty-three studies were included, and data were charted according to study type. Several epidemiological and other observational studies gave evidence of risk factors and an association between suicidal ideation, suicidal behaviour, and tinnitus. However, there was no evidence of the direction of causality. Qualitative studies are indicated to explore the patient’s experience and understand the dynamics of any interaction between tinnitus and suicidal thoughts and behaviours. A theory-informed model of tinnitus and suicide needs to be developed to inform the development of interventions and how tinnitus patients are supported clinically. Full article

The landscape of cranial base surgery has undergone monumental transformations over the past several decades. This article serves as a comprehensive survey, detailing both the historical and current techniques and technologies that have propelled this field into an era of unprecedented capabilities and sophistication. In the prologue, we traverse the historical evolution from rudimentary interventions to the state-of-the-art neurosurgical methodologies that define today’s practice. Subsequent sections delve into the anatomical complexities of the anterior, middle, and posterior cranial fossa, shedding light on the intricacies that dictate surgical approaches. In a section dedicated to advanced techniques and modalities, we explore cutting-edge evolutions in minimally invasive procedures, pituitary surgery, and cranial base reconstruction. Here, we highlight the seamless integration of endocrinology, biomaterial science, and engineering into neurosurgical craftsmanship. The article emphasizes the paradigm shift towards “Functionally” Guided Surgery facilitated by intraoperative neuromonitoring. We explore its historical origins, current technologies, and its invaluable role in tailoring surgical interventions across diverse pathologies. Additionally, the digital era’s contributions to cranial base surgery are examined. This includes breakthroughs in endoscopic technology, robotics, augmented reality, and the potential of machine learning and AI-assisted diagnostic and surgical planning. The discussion extends to radiosurgery and radiotherapy, focusing on the harmonization of precision and efficacy through advanced modalities such as Gamma Knife and CyberKnife. The article also evaluates newer protocols that optimize tumor control while preserving neural structures. In acknowledging the holistic nature of cranial base surgery, we advocate for an interdisciplinary approach. The ecosystem of this surgical field is presented as an amalgamation of various medical disciplines, including neurology, radiology, oncology, and rehabilitation, and is further enriched by insights from patient narratives and quality-of-life metrics. The epilogue contemplates future challenges and opportunities, pinpointing potential breakthroughs in stem cell research, regenerative medicine, and genomic tailoring. Ultimately, the article reaffirms the ethos of continuous learning, global collaboration, and patient-first principles, projecting an optimistic trajectory for the field of cranial base surgery in the coming decade. Full article

The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients’ perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients’ view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith–Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients’ and clinicians’ perspectives, although with some differential effects on specific symptoms at given time-points. Including patients’ viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions. Full article

Objective: The structural covariance network (SCN) alterations in patients with temporal lobe epilepsy and comorbid sleep disorder (PWSD) remain poorly understood. This study aimed to investigate changes in SCNs using structural magnetic resonance imaging. Methods: Thirty-four PWSD patients, thirty-three patients with temporal lobe epilepsy without sleep disorder (PWoSD), and seventeen healthy controls underwent high-resolution structural MRI imaging. Subsequently, SCNs were constructed based on gray matter volume and analyzed via graph-theoretical approaches. Results: PWSD exhibited significantly increased clustering coefficients, shortest path lengths, transitivity, and local efficiency. In addition, various distributions and numbers of SCN hubs were identified in PWSD. Furthermore, PWSD networks were less robust to random and target attacks than those of healthy controls and PWoSD patients. Conclusion: This study identifies aberrant SCN changes in PWSD that may be related to the susceptibility of patients with epilepsy to sleep disorders. Full article

(1) Background: Exposure to different sources of stress can have a significant effect on both psychological and physical processes. (2) Methods: The study took place over a period of 34 days and included a total of 40 animals. Regarding the exposure to chronic stressors, we opted for physiological, non-invasive stressors, e.g., running, swimming, and changes in the intensity of light. An unforeseen stress batch was also created that alternated all these stress factors. The animals were divided into five experimental groups, each consisting of eight individuals. In the context of conducting the open field test for behavioral assessment before and after stress exposure, we aimed to investigate the impact of stress exposure on the affective traits of the animals. We also monitored body mass every two days. (3) Results: The control group exhibited an average increase in weight of approximately 30%. The groups exposed to stress factors showed slower growth rates, the lowest being the running group, recording a rate of 20.55%, and the unpredictable stress group at 24.02%. The anxious behavior intensified in the group with unforeseen stress, in the one with light variations, and in the running group. (4) Conclusions: Our research validates the animal model of intermittent light exposure during the dark phase as a novel method of inducing stress. The modification of some anxiety parameters was observed; they vary according to the type of stress. Body mass was found to increase in all groups, especially in the sedentary groups, likely due to the absence of cognitive, spatial, and social stimuli except for cohabitation. Full article

The aim of this study is to evaluate the effectiveness of electrosuit therapy in the clinical treatment of children with Cerebral Palsy, focusing on the effect of the therapy on spasticity and trunk control. Moreover, the compliance of caregivers with respect to the use of the tool was investigated. During the period ranging from 2019 to 2022, a total of 26 children (18 M and 8 F), clinically stable and affected by CP and attending the Neurorehabilitation Unit of the “Padre Pio Foundation and Rehabilitation Centers”, were enrolled in this study. A subset of 12 patients bought or rented the device; thus, they received the administration of the EMS-based therapy for one month, whereas the others received only one-hour training to evaluate the feasibility (by the caregivers) and short-term effects. The Gross Motor Function Classification System was utilized to evaluate gross motor functions and to classify the study sample, while the MAS and the LSS were employed to assess the outcomes of the EMS-based therapy. Moreover, between 80% and 90% of the study sample were satisfied with the safety, ease of use, comfort, adjustment, and after-sales service. Following a single session of electrical stimulation with EMS, patients exhibited a statistically significant enhancement in trunk control. For those who continued this study, the subscale of the QUEST with the best score was adaptability (0.74 ± 0.85), followed by competence (0.67 ± 0.70) and self-esteem (0.59 ± 0.60). This study investigates the impact of the employment of the EMS on CP children’s ability to maintain trunk control. Specifically, after undergoing a single EMS session, LSS showed a discernible improvement in children’s trunk control. In addition, the QUEST and the PIADS questionnaires demonstrated a good acceptability and satisfaction of the garment by the patients and the caregivers. Full article

(1) Background: Incomplete excision of vestibular schwannomas (VSs) is sometimes preferable for facial nerve preservation. On the other hand, subtotal resection may be associated with higher tumor recurrence. We evaluated the correlation between intra-operative assessment of residual tumor and early and follow-up imaging. (2) Methods: The charts of all patients undergoing primary surgery for sporadic vestibular schwannoma during the study period were retrospectively reviewed. Data regarding surgeons’ assessments of the extent of resection, and the residual size of the tumor on post-operative day (POD) one and follow-up MRI were extracted. (3) Results: Of 109 vestibular schwannomas meeting inclusion criteria, gross-total resection (GTR) was achieved in eighty-four, near-total (NTR) and sub-total resection (STR) in twenty-two and three patients, respectively. On follow up imaging, volumetric analysis revealed that of twenty-two NTRs, eight were radiographic GTR and nine were radiographic STR (mean volume ratio 11.9%), while five remained NTR (mean volume ratio 1.8%). Of the three STRs, two were radiographic GTR while one remained STR. Therefore, of eighteen patients with available later follow up MRIs, radiographic classification of the degree of resection changed in six. (4) Conclusions: An early MRI (POD#1) establishes a baseline for the residual tumor that may be more accurate than the surgeon’s intraoperative assessment and may provide a beneficial point of comparison for long-term surveillance. Full article

Promoting active and successful aging has become crucial to improve quality of life in later adulthood and reduce the impact of cognitive decline. Increasing evidence suggested that the ability to think creatively (e.g., via divergent thinking), similar to cognitive reserve, could represent a beneficial factor against the negative effects of aging. However, there is still little evidence investigating the relationships between divergent thinking, cognitive functions, and cognitive reserve in late adulthood. The present study explored these relationships in a sample of 98 individuals ranging from 61 to 88 years old (mean age: 72.44 ± 6.35). Results showed that visual, but not verbal, divergent thinking was affected by aging. Interestingly, visual divergent thinking performance was predicted by both the cognitive component of crystallized intelligence and cognitive reserve. Only the crystallized component of intelligence was found to mediate the aging effect on visual divergent thinking performance. These results suggest that in later adulthood a potential shift strategy to prior knowledge and semantic components over executive and control components of cognition could underlie a preserved ability to think divergently and, plausibly, creatively. Limitations of the study and implications for successful aging are discussed. Full article

Stepping to recover balance is an important way we avoid falling. However, when faced with obstacles in the step path, we must adapt such reactions. Physical obstructions are typically detected through vision, which then cues step modification. The present study describes a novel method to assess visually prompted step inhibition in a reactive balance context. In our task, participants recovered balance by quickly stepping after being released from a supported forward lean. On rare trials, however, an obstacle blocked the stepping path. The timing of vision relative to postural perturbation was controlled using occlusion goggles to regulate task difficulty. Furthermore, we explored step suppression in our balance task related to inhibitory capacity measured at the hand using a clinically feasible handheld device (ReacStick). Our results showed that ReacStick and step outcomes were significantly correlated in terms of successful inhibition (r = 0.57) and overall reaction accuracy (r = 0.76). This study presents a novel method for assessing rapid inhibition in a dynamic postural context, a capacity that appears to be a necessary prerequisite to a subsequent adaptive strategy. Moreover, this capacity is significantly related to ReacStick performance, suggesting a potential clinical translation. Full article

(1) Background: Patients with vestibular migraine (VM) often present with positional vertigo. A portion of these patients have features of benign paroxysmal positional vertigo (BPPV). It is a challenge to rapidly identify the BPPV component of VM associated with positional vertigo. (2) Methods: Retrospective data collected from 60 VM and 47 VM + BPPV patients were used to build a diagnostic model, and then prospective data from 47 patients were used for the external validation. All patients had VM manifesting as positional vertigo, with or without accompanying BPPV. The clinical manifestations and the results of vestibular function tests were comprehensively analyzed using logistic regression. (3) Results: The univariate and multivariate analyses showed that the age, symptom duration, tinnitus, ear fullness, nausea, head shaking nystagmus, the direction of the Dix–Hallpike and roll tests, and horizontal gain could help differentiate between the two groups. A nomogram and an online calculator were generated. The C-index was 0.870. The diagnostic model showed good discriminative power and calibration performance during internal and external validation. (4) Conclusions: This study provided a new perspective for diagnosing VM with positional vertigo by identifying the BPPV component and, for the first time, offers a prediction model integrating multiple predictors. Full article

Workplace bullying is a prevalent issue with a significant impact on employees’ mental health. This study aimed to explore the relationship between workplace bullying and the prevalence of depression, with a particular focus on the role of gender. A total of 12,344 Korean employees aged 19–65 years were included in the study. They completed the Center for Epidemiologic Studies Depression Scale (CES-D) and a score of 16 or higher in CES-D indicated depression. The association between workplace bullying and depression was analyzed using logistic regression analyses. The average CES-D scores were higher for both male and female employees who experienced bullying than for those who did not (p < 0.001). The association between the experience of workplace bullying and the prevalence of depression was statistically significant for both genders, with a stronger correlation observed among male employees (p for interaction < 0.001). Organizations are urged to address workplace bullying, particularly for male employees, through the implementation of anti-bullying strategies and policies, as well as the provision of mental health resources and support. Full article

Background: Fibromyalgia (FM) and major depression disorder (MDD) frequently co-occur. Both disorders may share common serotonergic alterations, although there is less evidence of such alterations in FM. It is also unclear as to whether these alterations are persistent over time or transient. The objectives of this study were to (i) examine the changes in mRNA expression of serotonin transporter (SERT) on the surface of peripheral blood mononuclear cells (PBMCs) in FM, MDD, and the FM + MDD subjects compared to healthy controls, and to (ii) evaluate the effect of drug treatment on SERT expression. Methods: PBMCs were isolated from FM, MDD, FM + MDD, and control subjects. SERT expression was analyzed at the mRNA level via quantitative real-time polymerase chain reaction. Statistical analyses were performed using analyses of variance and linear mixed-effects models. Results: SERT mRNA expression was significantly reduced in MDD subjects compared to controls (p < 0.001), but not in FM nor in FM + MDD subjects. Although the drug treatments improved symptoms in FM, MDD, and FM + MDD subjects, they had no significant effect on SERT mRNA expression. Conclusions: These results corroborate the role of the SERT in the pathophysiology of MDD, but not in FM, and show that the decreased mRNA expression of SERT is a persistent, rather than transient, phenomenon. Full article

This study aims to explore the effect of cochlear implantation on tinnitus perception. A prospective study was conducted on 72 adult hearing-impaired patients to evaluate tinnitus perception before and after cochlear implantation, using standardized tinnitus questionnaires (the tinnitus sample case-history questionnaire, tinnitus functional index (TFI), and tinnitus handicap inventory (THI)). A large variety of demographic and hearing- and implant-related data was collected from patient hospital records to explore possible associations with the implantation effect. The prevalence of tinnitus complaints before implantation was 58.3%. The temporary induction or aggravation of tinnitus immediately after surgery was noted in 20% and 46.7% of patients, respectively. When evaluated 3 months after implantation, 60% of tinnitus patients experienced a clinically significant reduction in their complaints; most of the improvements were experienced immediately after activation of the implant. Only the scores for TFI and THI at baseline were found to be significantly correlated with a reduction in TFI scores after implantation. In 80% of tinnitus patients, the tinnitus remained suppressed for some time after taking off the device. The large subset of patients with residual inhibition supports the involvement of central pathophysiological processes in implantation effects on tinnitus, which are explored in this paper. Full article

Background: The prognosis of diffuse midline glioma (DMG) patients with H3K27M (H3K27M-DMG) alterations is poor; however, a model that encourages accurate prediction of prognosis for such lesions on an individual basis remains elusive. We aimed to construct an H3K27M-DMG survival model based on DeepSurv to predict patient prognosis. Methods: Patients recruited from a single center were used for model training, and patients recruited from another center were used for external validation. Univariate and multivariate Cox regression analyses were used to select features. Four machine learning models were constructed, and the consistency index (C-index) and integrated Brier score (IBS) were calculated. We used the receiver operating characteristic curve (ROC) and area under the receiver operating characteristic (AUC) curve to assess the accuracy of predicting 6-month, 12-month, 18-month and 24-month survival rates. A heatmap of feature importance was used to explain the results of the four models. Results: We recruited 113 patients in the training set and 23 patients in the test set. We included tumor size, tumor location, Karnofsky Performance Scale (KPS) score, enhancement, radiotherapy, and chemotherapy for model training. The accuracy of DeepSurv prediction is highest among the four models, with C-indexes of 0.862 and 0.811 in the training and external test sets, respectively. The DeepSurv model had the highest AUC values at 6 months, 12 months, 18 months and 24 months, which were 0.970 (0.919–1), 0.950 (0.877–1), 0.939 (0.845–1), and 0.875 (0.690–1), respectively. We designed an interactive interface to more intuitively display the survival probability prediction results provided by the DeepSurv model. Conclusion: The DeepSurv model outperforms traditional machine learning models in terms of prediction accuracy and robustness, and it can also provide personalized treatment recommendations for patients. The DeepSurv model may provide decision-making assistance for patients in formulating treatment plans in the future. Full article

In modern society, the time and duration of sleep on workdays are primarily determined by external factors, e.g., the alarm clock. This can lead to a misalignment of the intrinsically determined sleep timing, which is dependent on the individual chronotype, resulting in reduced sleep quality. Although this is highly relevant given the high incidence of sleep disorders, little is known about the effect of this misalignment on sleep architecture. Using Fitbit trackers and questionnaire surveys, our study aims to elucidate sleep timing, sleep architecture, and subjective sleep quality in young healthy adults (n = 59) under real-life conditions (average of 82.4 ± 9.7 days). Correlations between variables were calculated to identify the direction of relationships. On workdays, the midpoint of sleep was earlier, the sleep duration was shorter, and tiredness upon waking was higher than on free days. A higher discrepancy between sleep duration on workdays and free days was associated with a lower stability of the circadian rhythm of REM sleep and also with a higher fragmentation of REM sleep. Similarly, a higher tiredness upon waking on free days, thus under intrinsically determined sleep timing conditions, was associated with a lower proportion and a higher fragmentation of REM sleep. This suggests that the misalignment between extrinsically and intrinsically determined sleep timing affects the architecture of sleep stages, particularly REM sleep, which is closely connected to sleep quality. Full article

Not all elements displayed in a YouTube in-stream video ad are attributable to the ad itself. Some of those are automatically introduced by the platform, such as the countdown timer and the time progress bar. In recent years, some authors started exploring the effects associated with the presence of such non-ad items, providing valuable findings. However, objective evaluation of viewers’ visual attention is lacking in this context as well as emotional investigation. In addition, previous research showed how the manipulation of seemingly negligible details can yield dramatically different outcomes in the context of in-stream advertising. To extend knowledge, the authors explored the effects of the non-ad items’ presence by employing eye-tracking and facial coding techniques in combination with self-reports in a between-subjects experimental design focusing on the YouTube 15-s, mid-roll, non-skippable in-stream ad format. Results showed that the ad format currently employed by YouTube performs worse than its equivalent without the non-ad items on all the investigated measures and than its equivalent in which the non-ad items’ presence was experimentally reduced on facial coding disgust, self-reported disgust, ad irritation, and ad attitude. Managerial insights and challenges concerning the future of in-stream advertising and neuromarketing are highlighted. Full article

Combined antiretroviral therapy (cART) has greatly reduced the severity of HIV-associated neurocognitive disorders in people living with HIV (PLWH); however, PLWH are more likely than the general population to use drugs and suffer from substance use disorders (SUDs) and to exhibit risky behaviors that promote HIV transmission and other infections. Dopamine-boosting psychostimulants such as cocaine and methamphetamine are some of the most widely used substances among PLWH. Chronic use of these substances disrupts brain function, structure, and cognition. PLWH with SUD have poor health outcomes driven by complex interactions between biological, neurocognitive, and social factors. Here we review the effects of comorbid HIV and psychostimulant use disorders by discussing the distinct and common effects of HIV and chronic cocaine and methamphetamine use on behavioral and neurological impairments using evidence from rodent models of HIV-associated neurocognitive impairments (Tat or gp120 protein expression) and clinical studies. We also provide a biopsychosocial perspective by discussing behavioral impairment in differentially impacted social groups and proposing interventions at both patient and population levels. 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

When reading, dyslexic readers exhibit more and longer fixations than normal readers. However, there is no significant difference when dyslexic and control readers perform only visual tasks on a string of letters, showing the importance of cognitive processes in reading. This linguistic and cognitive processing requirement in reading is often perturbed for dyslexic readers by perceived additional letters and word mirror images superposed on the primary images on the primary cortex, inducing internal visual crowding. Here, we show that while for a normal reader, the number and the duration of fixations remain invariant whatever the nature of the lighting, the excess of fixations and total duration of reading can be controlled for a dyslexic reader using the Hebbian mechanisms to erase extra images in optimized pulse-width lighting. In this case, the number of fixations can then be reduced by a factor of about 1.8, recovering the normal reading experiment. Full article

Malignant glioma is a highly invasive tumor, and elucidating the glioma invasion mechanism is essential for developing novel therapies. We aimed to highlight actin alpha 2, smooth muscle (ACTA2) as potential biomarkers of brain invasion and distant recurrence in malignant gliomas. Using the human malignant glioma cell line, U251MG, we generated ACTA2 knockdown (KD) cells treated with small interfering RNA, and the cell motility and proliferation of the ACTA2 KD group were analyzed. Furthermore, tumor samples from 12 glioma patients who underwent reoperation at the time of tumor recurrence were utilized to measure ACTA2 expression in the tumors before and after recurrence. Thereafter, we examined how ACTA2 expression correlates with the time to tumor recurrence and the mode of recurrence. The results showed that the ACTA2 KD group demonstrated a decline in the mean motion distance and proliferative capacity compared to the control group. In the clinical glioma samples, ACTA2 expression was remarkably increased in recurrent samples compared to the primary samples from the same patients, and the higher the change in ACTCA2 expression from the start to relapse, the shorter the progression-free survival. In conclusion, ACTA2 may be involved in distant recurrence in clinical gliomas. Full article

Titanium middle ear (ME) prostheses are widely used in surgical practice due to their acoustic properties. However, they present a significant drawback shared by all synthetic materials currently in use for ME reconstruction: they can be rejected by the organism of the host. In this study, we aim to review the current literature on titanium partial ossicular replacement prostheses (PORPs) and total ossicular replacement prostheses (TORPs) extrusion and dislocation. Eighty articles were analysed after a full article review based on the inclusion and exclusion criteria. The most common indication for reconstruction was chronic otitis media with cholesteatoma. The average extrusion or dislocation rate was 5.2%, ranging from 0 to 35%. The average improvements in the air–bone gap were 12.1 dB (1.6 dB to 25.1 dB) and 13.8 (−0.5 dB to 22.7 dB) for the PORP and TORP groups, respectively. The data reported on this topic are highly variable, demonstrating that functional outcomes are difficult to predict in clinical practice. We believe that the current limitations could be overcome with technological developments, including bioengineering research focused on promoting prosthesis adaptation to the ME environment. Full article

Major depressive disorder (MDD) is one of the most common neuropsychiatric disorders, with symptoms including persistent sadness and loss of interest. MDD is associated with neurochemical alterations in GABA, glutamate, and glutamine levels but, to date, few studies have examined changes in glutathione (GSH) in MDD. This study investigated changes in GSH in an unmedicated group of young adults, including 46 participants with current (n = 12) or past MDD (n = 34) and 20 healthy controls. Glutathione levels were assessed from GSH-edited magnetic resonance (MR) spectra, acquired from a voxel in the left prefrontal cortex, and depressive symptoms were evaluated with validated questionnaires and clinical assessments. Cortisol levels were also assessed as a marker for acute stress. Participants with current MDD demonstrated elevated GSH in comparison to participants with past MDD and controls, although the results could be influenced by differences in tissue composition within the MRS voxel. In addition, participants with both current and past MDD showed elevated cortisol levels in comparison to controls. No significant association was observed between GSH and cortisol levels, but elevated GSH levels were associated with a decrease in positive affect. These results demonstrate for the first time that elevated GSH in current but not past depression may reflect a state rather than a trait neurobiological change, related to a loss of positive affect. Full article

Frontotemporal lobar degeneration (FTLD) belongs to a heterogeneous group of highly complex neurodegenerative diseases and represents the second cause of presenile dementia in individuals under 65. Frontotemporal-TDP is a subgroup of frontotemporal dementia characterized by the aggregation of abnormal protein deposits, predominantly transactive response DNA-binding protein 43 (TDP-43), in the frontal and temporal brain regions. These deposits lead to progressive degeneration of neurons resulting in cognitive and behavioral impairments. Limbic age-related encephalopathy (LATE) pertains to age-related cognitive decline primarily affecting the limbic system, which is crucial for memory, emotions, and learning. However, distinct, emerging research suggests a potential overlap in pathogenic processes, with some cases of limbic encephalopathy displaying TDP-43 pathology. Genetic factors play a pivotal role in both disorders. Mutations in various genes, such as progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72), have been identified as causative in frontotemporal-TDP. Similarly, specific genetic variants have been associated with an increased risk of developing LATE. Understanding these genetic links provides crucial insights into disease mechanisms and the potential for targeted therapies. Full article

Mentalizing, recognized as the capacity to understand behaviors in the context of our own mental states and those of other people, is being researched more and more commonly in regard to various mental disorders. The research on mentalization focuses on, among other things, borderline personality disorder, which is at present perceived as an emerging problem in the population of adolescents. In order to summarize the currently accessible knowledge of mentalizing in adolescents with borderline personality disorder, we thoroughly analyzed relevant publications. Based on the available literature, it can be concluded that the mentalizing ability of adolescents with borderline personality disorder can be impaired. The evidence demonstrates that they are prone to hypermentalizing, defined as an overattribution of mental states to other people. However, this tendency has not been proven to be specific to teenagers with this disorder. Moreover, the existing data suggest that young people with borderline personality exhibit a reduced capacity to mentalize their own inner states. Full article

Elevated glucocorticoid levels triggered by stress potentially contribute to sleep disturbances in stress-induced depression. However, sleep changes in response to elevated corticosterone (CORT), the major glucocorticoid in rodents, remain unclear. Here, we investigated the effects of acute or chronic CORT administration on sleep using electroencephalogram (EEG) and electromyography (EMG) recordings in freely moving mice. Acute CORT exposure rapidly promoted wakefulness, marked by increased episodes and enhanced EEG delta power, while simultaneously suppressing rapid eye movement (REM) and non-rapid eye movement (NREM) sleep, with the latter marked by decreased mean duration and reduced delta power. Prolonged 28-day CORT exposure led to excessive wakefulness and REM sleep, characterized by higher episodes, and decreased NREM sleep, characterized by higher episodes and reduced mean duration. EEG theta activity during REM sleep and delta activity during NREM sleep were attenuated following 28-day CORT exposure. These effects persisted, except for REM sleep amounts, even 7 days after the drug withdrawal. Elevated plasma CORT levels and depressive phenotypes were identified and correlated with observed sleep changes during and after administration. Fos expression significantly increased in the lateral habenula, lateral hypothalamus, and ventral tegmental area following acute or chronic CORT treatment. Our findings demonstrate that CORT exposure enhanced wakefulness, suppressed and fragmented NREM sleep, and altered EEG activity across all stages. This study illuminates sleep alterations during short or extended periods of heightened CORT levels in mice, providing a neural link connecting insomnia and depression. Full article

Cardiac sympathetic denervation, as documented on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, is relatively sensitive and specific for distinguishing Parkinson’s disease (PD) from other neurodegenerative causes of parkinsonism. The present study aims to comprehensively review the literature regarding the use of cardiac MIBG in PD. MIBG is an analog to norepinephrine. They share the same uptake, storage, and release mechanisms. An abnormal result in the cardiac MIBG uptake in individuals with parkinsonism can be an additional criterion for diagnosing PD. However, a normal result of cardiac MIBG in individuals with suspicious parkinsonian syndrome does not exclude the diagnosis of PD. The findings of cardiac MIBG studies contributed to elucidating the pathophysiology of PD. We investigated the sensitivity and specificity of cardiac MIBG scintigraphy in PD. A total of 54 studies with 3114 individuals diagnosed with PD were included. The data were described as means with a Hoehn and Yahr stage of 2.5 and early and delayed registration H/M ratios of 1.70 and 1.51, respectively. The mean cutoff for the early and delayed phases were 1.89 and 1.86. The sensitivity for the early and delayed phases was 0.81 and 0.83, respectively. The specificity for the early and delayed phases were 0.86 and 0.80, respectively. Full article