Brain Sci., Volume 13, Issue 7 (July 2023) – 146 articles

The role of the endoscopic transplanum–transtuberculum approach (ETTA) in the treatment of pituitary adenomas/PitNETs (PAs) is sparsely analyzed in the literature, and its use is still debated in the current practice. The aim of this study was to report our experience with this approach. Our institutional registry was retrospectively reviewed, and patients who underwent ETTA for a PA from 1998 to 2022 were included. Fifty-seven cases were enrolled over a time span of 25 years, corresponding to 2.4% of our entire PA caseload. Radical resection was achieved in 57.9% of cases, with re-do surgery (p = 0.033) and vessel encasement/engulfment (p < 0.001) as predictors of partial resection. CSF leak incidence stood at 8.8%, with higher BMI (p = 0.038) as its only significant predictor. Partial or full improvement of the visual field deficits was achieved in 73.5% of cases. No surgical mortality was observed. According to our results, ETTA for the treatment of PAs is characterized by a satisfactory surgical outcome but with greater morbidity than the conventional endoscopic approach. Therefore, it should be reserved for the few selected cases otherwise unsuitable for the endoscopic trans-sphenoidal route, representing a valid alternative and an effective complementary route for the transcranial approach for these challenging PAs. Full article

Previous studies set out profound cognitive impairments in subjects with treatment-resistant depression (TRD). However, little is known about the course of such alterations depending on levels of improvement in those patients followed longitudinally. The main objective of this study was to describe the course of cognitive impairments in responder versus non-responder TRD patients at one-year follow-up. The second aim was to evaluate the predictive aspect of cognitive impairments to treatment resistance in patients suffering from TRD. We included 131 patients from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centers. They undertook comprehensive sociodemographic, clinical, global functioning, and neuropsychological testing (TMT, Baddeley task, verbal fluencies, WAIS-4 subtests, D2 and RLRI-16) at baseline (V0) and one-year follow-up (V1). Most patients (n = 83; 63.36%) did not respond (47 women, 49.47 ± 12.64 years old), while one-third of patients responded (n = 48, 30 women, 54.06 ± 12.03 years old). We compared the cognitive performances of participants to average theoretical performances in the general population. In addition, we compared the cognitive performances of patients between V1 and V0 and responder versus non-responder patients at V1. We observed cognitive impairments during the episode and after a therapeutic response. Overall, each of them tended to show an increase in their cognitive scores. Improvement was more prominent in responders at V1 compared to their non-responder counterparts. They experienced a more marked improvement in code, digit span, arithmetic, similarities, and D2 tasks. Patients suffering from TRD have significant cognitive impairments that persist but alleviate after therapeutic response. Cognitive remediation should be proposed after therapeutic response to improve efficiency and increase the daily functioning. Full article

Background and Objective: Dietary constituents may affect the progression of Parkinson’s disease (PD). This study aimed to assess the contribution of dietary intake of vitamins and minerals to the severity, motor and non-motor symptoms, and risk of PD. Methods: In this case-control study, 120 patients with PD and 50 healthy participants participated. Dietary intake of vitamins and minerals was determined using a 147-item food frequency questionnaire. The severity of PD was determined by the Unified Parkinson’s Disease Rating Scale (UPDRS). Results: Patients with PD had lower intake of several vitamins and minerals including lycopene, thiamine, vitamin B6, vitamin B12, pantothenic acid, magnesium, zinc, manganese, selenium, chromium, and phosphorus, but had higher intake of α-tocopherol. High dietary intake of vitamin A, α-carotene, β-cryptoxanthin, vitamin C, and α-tocopherol were correlated with increased odds of PD. High intake of lycopene, thiamin, vitamin B6, pantothenic acid, magnesium, zinc, manganese, chromium, and phosphorous correlated with reduced odds of PD. The predictive power of α-tocopherol concerning the risk of PD was stronger relative to other vitamins. Dietary intake of pantothenic acid was negatively correlated with PD severity and symptoms of motor examination and complication. The severity and motor symptoms of PD were also negatively correlated with β-carotene, vitamin C, riboflavin, vitamin B6, and biotin intake. The UPDRS total score and motor symptoms in PD patients were negatively correlated with phosphorus, magnesium, zinc, manganese, and chromium, and strongly with potassium intake. Conclusion: The findings indicate that adequate dietary intake of vitamins and minerals may have a preventive effect on developing PD and progression of motor decline. Full article

(1) Background: Intimate partner violence (IPV) is a pervasive and destructive phenomenon. There is a need for an integrated and comprehensive approach to IPV in order to align prevention, support and treatment. Still little is known about the cognitive and affective markers of IPV that are modifiable. Such knowledge, therefore, can support the effectiveness of prevention and intervention programs. In this study, we put forward a hypothesis that, after accounting for the influence of sociodemographic variables, the domains of early maladaptive schemas (EMS) and strategic emotional intelligence would provide additional information for predicting female IPV victimization. (2) Methods: 48 female survivors of IPV and 48 age-matched women with no prior experience of IPV completed the Young Schema Questionnaire-Short Form 3 (YSQ-SF3) and The Emotional Understanding Test (TRE). (3) Results: The domains of disconnection and rejection and impaired limits were significant predictors of IPV victimization, but the results did not support the predictive value for impaired autonomy, other-directedness and strategic emotional intelligence. (4) Conclusions: Our findings add to the emerging evidence of a link between disconnection and rejection domain and IPV victimization. As a consequence, maladaptive beliefs that interpersonal relationships are unstable and insecure and expose to the risk of humiliation and harm, and that basic emotional needs cannot be satisfied in close relationships, are associated with a higher risk of intimate partner violence. In this context, schema therapy appears to be a promising support for IPV victims. Full article

Headaches are common after ischemic stroke (IS). Unlike primary headaches, headaches attributed to IS have specific clinical features. This review describes the epidemiology, clinical characteristics, risk factors, and influence of IS headaches. Previous reports were summarized to show the correlations between headaches and structural lesions in the cerebral cortex, subcortical white matter, deep gray matter nuclei, brainstem, and cerebellum. However, the substantial heterogeneity of IS, subjective evaluations of headaches, and inadequate cohort studies make it difficult to explore the pathophysiology of headaches attributed to IS. In our recommendation, favorable imaging techniques, such as magnetic resonance imaging and positron emission tomography, may provide new insights into mechanical studies of IS headaches from structure to function. It may also be helpful to extend the research field by targeting several shared signal transducers between headaches and IS. These markers might be neuropeptides, vasoactive substances, ion channels, or electrophysiologic changes. Full article

The aim of this study is to review the available literature investigating the relationship between hikikomori, a pathological condition characterized by severe social withdrawal or isolation, autism spectrum disorder (ASD) and Internet gaming disorder (IGD). Studies on the relationship between ASD and IGD have found significant positive correlations between these two conditions. Individuals with ASD would appear to be at risk of developing a problematic use of the Internet, which, to the right extent, would represent a useful tool for social interaction and cognitive development. Even subjects with hikikomori, in whom rarefied interpersonal relationships and social isolation could be balanced by the use of online connections, appear to be at high risk of developing IGD. On the other hand, the finding of significant autistic traits in populations with hikikomori could lead to considering this psychopathological condition as a particular presentation of autism spectrum, a hypothesis that requires further investigation. Full article

Brain aging has been correlated with high metallothionein I-II (MT-I/II) expression, iron and zinc dyshomeostasis, and Aβ deposition in humans and experimental animals. In the present study, iron and zinc accumulation, the expression of MT-I/II and Aβ42, and their potential association with aging in the feline brain were assessed. Tissue sections from the temporal and frontal grey (GM) and white (WM) matter, hippocampus, thalamus, striatum, cerebellum, and dentate nucleus were examined histochemically for the presence of age-related histopathological lesions and iron deposits and distribution. We found, using a modified Perl’s/DAB method, two types of iron plaques that showed age-dependent accumulation in the temporal GM and WM and the thalamus, along with the age-dependent increment in cerebellar-myelin-associated iron. We also demonstrated an age-dependent increase in MT-I/II immunoreactivity in the feline brain. In cats over 7 years old, Aβ immunoreactivity was detected in vessel walls and neuronal somata; extracellular Aβ deposits were also evident. Interestingly, Aβ-positive astrocytes were also observed in certain cases. ICP-MS analysis of brain content regarding iron and zinc concentrations showed no statistically significant association with age, but a mild increase in iron with age was noticed, while zinc levels were found to be higher in the Mature and Senior groups. Our findings reinforce the suggestion that cats could serve as a dependable natural animal model for brain aging and neurodegeneration; thus, they should be further investigated on the basis of metal ion concentration changes and their effects on aging. Full article

The COVID-19 pandemic introduced unprecedented challenges in managing patients with Parkinson’s disease (PD) due to disruptions in healthcare services and the need for social distancing. Understanding the effects of COVID-19 on PD symptoms is crucial for optimizing patient care. We conducted a comprehensive analysis of the data obtained during the period of COVID-19 lockdown, comparing it with analogous timeframes in 2018 and 2019. Our objective was to examine the influence of this unique circumstance on both motor and non-motor symptoms in patients with PD. Telemedicine was employed to assess symptoms using the Movement Disorder Society-sponsored Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). Our findings revealed a notable worsening of symptoms, evidenced by a significant increase in the total MDS-UPDRS score. Specifically, there was an increase in Part III scores, reflecting changes in motor function. However, no differences were observed in Parts I or II, which pertain to non-motor symptoms. Additionally, patient satisfaction and the feasibility of telemedicine consultations were high, highlighting the efficacy of this alternative approach during the pandemic. The COVID-19 pandemic had a discernible impact on PD symptoms, with a significant worsening of motor symptoms observed during the lockdown period. Telemedicine was a valuable tool for remote assessment and follow-up, ensuring continuity of care for individuals with PD in the face of pandemic-related challenges. Full article

Previous studies suggest that producing and comprehending semantically related words relies on inhibitory control over competitive lexical selection which results in the recruitment of the left inferior frontal gyrus (IFG). Few studies, however, have examined the involvement of other regions of the frontal cortex, such as the dorsolateral prefrontal cortex (DLPFC), despite its role in cognitive control related to lexical processing. The primary objective of this study was to elucidate the role of the DLPFC in the production and comprehension of semantically and phonologically related words in blocked cyclic naming and picture–word matching paradigms. Twenty-one adults participated in neuroimaging with functional near-infrared spectroscopy to measure changes in oxygenated and deoxygenated hemoglobin concentrations across the bilateral frontal cortex during blocked cyclic picture naming and blocked cyclic picture–word-matching tasks. After preprocessing, oxygenated and deoxygenated hemoglobin concentrations were obtained for each task (production, comprehension), condition (semantic, phonological) and region (DLPFC, IFG). The results of pairwise t-tests adjusted for multiple comparisons showed significant increases in oxygenated hemoglobin concentration over baseline in the bilateral DLPFC during picture naming for phonologically related words. For picture–word matching, we found significant increases in oxygenated hemoglobin concentration over baseline in the right DLPFC for semantically related words and in the right IFG for phonologically related words. We discuss the results in light of the inhibitory attentional control over competitive lexical access theory in contrast to alternative potential explanations for the findings. Full article

This randomized controlled trial aims to investigate the effect of 12 weeks of therapeutic exercise on cognitive function and daily activities in patients with mild Alzheimer’s disease (AD). A total of 171 patients with mild AD from the Amarousion Day Care Center of the Alzheimer Society of Athens and the Athens General Hospital “G. Gennimatas” were randomly divided into three groups. Group A (aerobic and resistance exercise, n = 57), group B (resistance exercise, n = 57), and group C (control group, n = 57). Group A followed a weekly program consisting of 5 days with 30 min walking and 3 days with resistance exercises for about 45 min. Group B followed only a resistance exercise program, the same as group A. Group C did not participate in any exercise program. After the intervention, cognitive function was assessed with the Cognitive Examination-Revised (ACE-R), Trail Making Test A-B (TMT A-B), and Digit Span Test Forward and Backward (DST F-B) and daily activities with the instrumental activities of daily living scale (IADLs). A significant intervention effect was observed for all outcome measures (global cognitive function and instrumental activities of daily living). ANCOVA Bonferroni corrected post hoc tests revealed that the aerobic and resistance group improved compared to the control group on all measurement scales. The resistance group also showed an improvement compared to the control group. No significant effects were found between the aerobic and resistance group and the resistance group in any of the outcome measures. Full article

Mild cognitive impairment (MCI) is an intermediate stage between normal aging and dementia, and a significant number of individuals with MCI progress to develop dementia. Depression is prevalent in MCI patients and has been found to influence the disease progression of MCI. The default mode network (DMN), a brain network associated with Alzheimer’s disease (AD), and its functional connectivity might be a neurological mechanism linking depression and AD. However, the relationship between depression, DMN functional connectivity, and cerebral beta-amyloid (Aβ) pathology remains unclear. This study aimed to investigate DMN functional connectivity differences in Aβ-positive MCI patients with depression compared to those without depression. A total of 126 Aβ-positive MCI patients were included, with 66 having depression and 60 without depression. The results revealed increased functional connectivity in the anterior DMN in the depression group compared to the non-depression group. The functional connectivity of the anterior DMN positively correlated with depression severity but not with Aβ deposition. Our findings suggest that depression influences DMN functional connectivity in Aβ-positive MCI patients, and the depression-associated DMN functional connectivity aberrance might be an important neural mechanism linking depression, Aβ pathology, and disease progression in the trajectory of AD. Full article

Habituation, the simplest form of learning preserved across species and evolution, is characterized by a response decrease as a stimulus is repeated. This adaptive function has been shown to be altered in some psychiatric and neurodevelopmental disorders such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) or schizophrenia. At the brain level, habituation is characterized by a decrease in neural activity as a stimulation is repeated, referred to as neural adaptation. This phenomenon influences the ability to make predictions and to detect change, two processes altered in some neurodevelopmental and psychiatric disorders. In this comprehensive review, the objectives are to characterize habituation, neural adaptation, and prediction throughout typical development and in neurodevelopmental disorders; and to evaluate their implication in symptomatology, specifically in sensitivity to change or need for sameness. A summary of the different approaches to investigate adaptation will be proposed, in which we report the contribution of animal studies as well as electrophysiological studies in humans to understanding of underlying neuronal mechanisms. Full article

A brain computer interface (BCI) system helps people with motor dysfunction interact with the external environment. With the advancement of technology, BCI systems have been applied in practice, but their practicability and usability are still greatly challenged. A large amount of calibration time is often required before BCI systems are used, which can consume the patient’s energy and easily lead to anxiety. This paper proposes a novel motion-assisted method based on a novel dual-branch multiscale auto encoder network (MSAENet) to decode human brain motion imagery intentions, while introducing a central loss function to compensate for the shortcomings of traditional classifiers that only consider inter-class differences and ignore intra-class coupling. The effectiveness of the method is validated on three datasets, namely BCIIV2a, SMR-BCI and OpenBMI, to achieve zero calibration of the MI-BCI system. The results show that our proposed network displays good results on all three datasets. In the case of subject-independence, the MSAENet outperformed the other four comparison methods on the BCIIV2a and SMR-BCI datasets, while achieving F1_score values as high as 69.34% on the OpenBMI dataset. Our method maintains better classification accuracy with a small number of parameters and short prediction times, and the method achieves zero calibration of the MI-BCI system. Full article

Aspirin has been reported to prevent memory decline in the elderly population. Adult neurogenesis in the hippocampus has been recognized as an underlying basis of learning and memory. This study investigated the effect of aspirin on spatial memory in correlation with the regulation of hippocampal neurogenesis and microglia in the brains of ageing experimental mice. Results from the novel object recognition (NOR) test, Morris water maze (MWM), and cued radial arm maze (cued RAM) revealed that aspirin treatment enhances working memory in experimental mice. Further, the co-immunohistochemical assessments on the brain sections indicated an increased number of doublecortin (DCX)-positive immature neurons and bromodeoxyuridine (BrdU)/neuronal nuclei (NeuN) double-positive newly generated neurons in the hippocampi of mice in the aspirin-treated group compared to the control group. Moreover, a reduced number of ionized calcium-binding adaptor molecule (Iba)-1-positive microglial cells was evident in the hippocampus of aspirin-treated animals. Recently, enhanced activity of acetylcholinesterase (AChE) in circulation has been identified as an indicative biomarker of dementia. The biochemical assessment in the blood of aspirin-treated mice showed decreased activity of AChE in comparison with that of the control group. Results from this study revealed that aspirin facilitates hippocampal neurogenesis which might be linked to enhanced working memory. Full article

Several studies have shown the positive effect of cerebellar transcranial direct current stimulation (ctDCS) on balance in patients and older adults. However, in healthy volunteers, the results are conflicting. We aimed to investigate the immediate effect of anodal ctDCS on the dynamic–static balance in healthy, non-athletic young adults due to the possible benefits for sports performance. Twenty-one healthy volunteers participated in two consecutive 20 min sessions of ctDCS (2 mA current intensity), with 1-week intervals (anodal ctDCS–sham ctDCS). Flamingo and Y-Balance tests were used to evaluate the static and dynamic balances before and after the ctDCS. A Continuous Performance Test (CPT) was used to evaluate the changes in sustained attention, impulsivity, and vigilance. A repeated measure analysis of variance (ANOVA) was used to compare the changes in balance scores, reaction time, omission, and commission numbers. There were no statistically significant differences in dynamic and static balance scores and in CPT parameters between conditions. In conclusion, there was no immediate neuromodulation effect of anodal ctDCS to improve balance performance in healthy, young individuals. Furthermore, no evidence was found to support the use of cerebellar tDCS to improve sports performance. Full article

Pediatric central nervous system (CNS) tumors are the most common solid tumor in children, with the majority being glial in origin. These tumors are classified by the World Health Organization (WHO) as either being low grade (WHO grade 1 and 2) or high grade (WHO grade 3 and 4). Our knowledge of the molecular landscape of pediatric brain tumors has advanced over the last decade, which has led to newer categorizations along with an expansion of therapeutic targets and options. In this review, we will give an overview of common CNS tumors seen in children along with a focus on treatment options and future considerations. Full article

Sensorimotor control can be impaired by slacked muscle spindles. This was shown for reflex responses and, recently, also for muscular stability in the sense of Adaptive Force (AF). The slack in muscle spindles was generated by contracting the lengthened muscle followed by passive shortening. AF was suggested to specifically reflect sensorimotor control since it requires tension-length control in adaptation to an increasing load. This study investigated AF parameters in reaction to another, manually performed slack procedure in a preselected sample (n = 13). The AF of 11 elbow and 12 hip flexors was assessed by an objectified manual muscle test (MMT) using a handheld device. Maximal isometric AF was significantly reduced after manual spindle technique vs. regular MMT. Muscle lengthening started at 64.93 ± 12.46% of maximal voluntary isometric contraction (MVIC). During regular MMT, muscle length could be maintained stable until 92.53 ± 10.12% of MVIC. Hence, muscular stability measured by AF was impaired after spindle manipulation. Force oscillations arose at a significantly lower level for regular vs. spindle. This supports the assumption that they are a prerequisite for stable adaptation. Reduced muscular stability in reaction to slack procedures is considered physiological since sensory information is misled. It is proposed to use slack procedures to test the functionality of the neuromuscular system, which is relevant for clinical practice. Full article

Sleep bruxism (SB) is a sleep-related behavior characterized as rhythmic (phasic) or non-rhythmic (tonic) masticatory muscle activity. SB is a common sleep behavior with a predominantly central origin. The aim of this systematic review was to evaluate the relationship between inflammatory status and SB according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020). The research was registered at PROSPERO (CRD42023395985). We performed a systematic literature analysis using five different databases. Furthermore, the backward snowballing technique was applied to identify additional papers. Initially, 28 papers were screened from the database search, and 162 papers were revealed in the backward snowballing process. Eventually, five articles were included. Data concerning the inflammatory status of patients experiencing SB were investigated and summarized. Due to the heterogeneity of the compared studies, only a qualitative comparison and narrative summary were performed. The results suggest that SB could be associated with systemic inflammation. In fact, this systematic review revealed that there are no papers conclusively showing that the inflammatory status in bruxers is comparable to non-bruxers. However, each of the examined studies utilized different methods of assessing systemic inflammation, which makes the results dubious. Full article

This quasi-experimental, nonrandomized intervention study reports the effect of person-centred, culturally appropriate music on psychological wellbeing of residents with advanced dementia in five rural residential aged care homes in Australia. Seventy-four residents attended in person-centred music sessions and culturally appropriate group sessions. Interest, response, initiation, involvement, enjoyment, and general reactions of the residents were assessed using the Music in Dementia Assessment Scale (MiDAS), and interviews and focus groups were conducted with aged care staff and musicians. The overall effect of person-centred sessions at two-time points were: during the intervention—351.2 (SD 93.5); and two-hours post intervention—315.1 (SD 98.5). The residents presented a moderate to high level of interest, response, initiation, involvement, and enjoyment during the session and at post-intervention. However, the MiDAS sub-categories’ mean scores differed between the time-points: interest (t₅₉ = 2.8, p = 0.001); response (t₅₉ = 2.9, p = 0.005); initiation (t₅₉ = 2.4, p = 0.019); and involvement (t₅₉ = 2.8, p = 0.007), indicating a significant decline in the effect of person-centred music over time. Interestingly, during the period of time, most of the residents were observed with no exhibitions of agitation (87.5%), low in mood (87.5%), and anxiousness (70.3%), and with a presentation of relaxation (75.5%), attentiveness (56.5%), and smiling (56.9%). Themes from qualitative data collected regarding culturally appropriate group music sessions were behavioural change, meaningful interaction, being initiative, increased participation, and contentment. The findings suggest that the integration of music into care plans may reduce the residents’ agitation and improve their emotional wellbeing in rural aged care homes. Full article

Unilateral spastic cerebral palsy (USCP) is caused by damage to the developing brain and affects motor function, mainly lateralized to one side of the body. Children with USCP have difficulties grasping objects, which can affect their ability to perform daily activities. Although cerebral palsy is typically classified according to motor function, sensory abnormalities are often present as well and may contribute to motor impairments, including grasping. In this review, we show that the integrity and connectivity pattern of the corticospinal tract (CST) is related to execution and anticipatory control of grasping. However, as this may not explain all the variance of impairments in grasping function, we also describe the potential roles of sensory and sensorimotor integration deficits that contribute to grasp impairments. We highlight studies measuring fingertip forces during object manipulation tasks, as this approach allows for the dissection of the close association of sensory and motor function and can detect the discriminant use of sensory information during a complex, functional task (i.e., grasping). In addition, we discuss the importance of examining the interactions of the sensory and motor systems together, rather than in isolation. Finally, we suggest future directions for research to understand the underlying mechanisms of grasp impairments. Full article

Background: Histamine is a widely distributed biogenic amine with multiple biological functions mediated by specific receptors that determine the local effects of histamine. This review aims to summarize the published findings on the expression and functional roles of histamine receptors in the inner ear and to identify potential research hotspots and gaps. Methods: A search of the electronic databases PubMed, Web of Science, and OVID EMBASE was performed using the keywords histamine, cochlea*, and inner ear. Of the 181 studies identified, 18 eligible publications were included in the full-text analysis. Results: All four types of histamine receptors were identified in the mammalian inner ear. The functional studies of histamine in the inner ear were mainly in vitro. Clinical evidence suggests that histamine and its receptors may play a role in Ménière’s disease, but the exact mechanism is not fully understood. The effects of histamine on hearing development remain unclear. Conclusions: Existing studies have successfully determined the expression of all four histamine receptors in the mammalian inner ear. However, further functional studies are needed to explore the potential of histamine receptors as targets for the treatment of hearing and balance disorders. Full article

Uni-hemispheric concurrent dual-site anodal transcranial direct current stimulation (UHCDS a-tDCS) of the primary motor cortex (M₁) and the dorsolateral prefrontal cortex (DLPFC) may enhance the efficacy of a-tDCS after stroke. However, the cellular and molecular mechanisms underlying its beneficial effects have not been defined. We aimed to investigate the effect of a-tDCS_M1-DLPFC on brain metabolite concentrations (N-acetyl aspartate (NAA), choline (Cho)) in stroke patients using magnetic resonance spectroscopy (MRS). In this double-blind, sham-controlled, randomized clinical trial (RCT), 18 patients with a first chronic stroke in the territory of the middle cerebral artery trunk were recruited. Patients were allocated to one of the following two groups: (1) Experimental 1, who received five consecutive sessions of a-tDCS_M1-DLPFC M₁ (active)-DLPFC (active). (2) Experimental 2, who received five consecutive sessions of a-tDCS_M1-DLPFC M1 (active)-DLPFC (sham). MRS assessments were performed before and 24 h after the last intervention. Results showed that after five sessions of a-tDCS_M1-DLPFC, there were no significant changes in NAA and Cho levels between groups (Cohen’s d = 1.4, Cohen’s d = 0.93). Thus, dual site a-tDCS_M1-DLPFC did not affect brain metabolites compared to single site a-tDCS M₁. Full article

The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain that can be associated with the progression of Alzheimer’s Disease (AD). To address this burden in type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (NCT04626453, NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well tolerated, even during the COVID-19 pandemic. It was also safe, requiring minimal equipment and no supervision. Our paper presents portable near-infrared spectroscopy (NIRS) based measures that showed muscle oxygen saturation (SmO2), i.e., the balance between oxygen delivery and oxygen consumption in muscle, drop during bilateral heel rise task (BHR) and the 6 min walk task (6MWT) significantly (p < 0.05) changed at the post-intervention follow-up from the pre-intervention baseline in the T2DM Intervention group participants. Moreover, post-intervention changes from pre-intervention baseline for the prefrontal activation (both oxyhemoglobin and deoxyhemoglobin) showed statistically significant (p < 0.05, q < 0.05) effect at the right superior frontal gyrus, dorsolateral, during the Mini-Cog task. Here, operational modal analysis provided further insights into the 2-month exercise intervention effects on the very-low-frequency oscillations (<0.05 Hz) during the Mini-Cog task that improved post-intervention in the sedentary T2DM Intervention group from their pre-intervention baseline when compared to active healthy Control group. Then, the 6MWT distance significantly (p < 0.01) improved in the T2DM Intervention group at post-intervention follow-up from pre-intervention baseline that showed improved aerobic capacity and endurance. Our portable NIRS based measures have practical implications at the point of care for the therapists as they can monitor muscle and brain oxygenation changes during physical and cognitive tests to prescribe personalized physical exercise doses without triggering individual stress response, thereby, enhancing vascular health in T2DM. Full article

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by abnormalities in structure and function of the brain. However, how ASD affects the relationship between fiber-bundle microstructures and functional connectivity (FC) remains unclear. Here, we analyzed structural and functional images of 26 high-functioning adult males with ASD, alongside 26 age-, gender-, and full-scale IQ-matched typically developing controls (TDCs) from the BNI dataset in the ABIDE database. We utilized fixel-based analysis to extract microstructural information from fiber tracts, which was then used to predict FC using a multilinear model. Our results revealed that the structure–function relationships in both ASD and TDC cohorts were strongly aligned in the primary cortex but decoupled in the high-order cortex, and the ASD patients exhibited reduced structure–function relationships throughout the cortex compared to the TDCs. Furthermore, we observed that the disrupted relationships in ASD were primarily driven by alterations in FC rather than fiber-bundle microstructures. The structure–function relationships in the left superior parietal cortex, right precentral and inferior temporal cortices, and bilateral insula could predict individual differences in clinical symptoms of ASD patients. These findings underscore the significance of altered relationships between fiber-bundle microstructures and FC in the etiology of ASD. Full article

Background and Purpose: Little is known about the effect of soluble adhesion molecules on malignant brain edema (MBE) after endovascular thrombectomy (EVT). This study aimed to explore the association between serum concentrations of E-selectin and the risk of MBE in patients who received EVT. Methods: Patients with a large vessel occlusion stroke in the anterior circulation who underwent EVT were prospectively recruited. Serum soluble E-selectin concentrations were measured after admission for all patients. MBE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 h after surgery. Multivariate logistic regression analyses were performed to determine the association between E-selectin levels and the risk of MBE. Results: Among the 261 included patients (mean age, 69.7 ± 12.3 years; 166 males), 59 (22.6%) developed MBE. Increasing circulating E-selectin levels were associated with an increased risk of MBE after multivariable adjustment (odds ratios [OR], highest vs. lowest quartile: 3.593; 95% confidence interval [CI], 1.178−10.956; p = 0.025). We further observed a significantly positive association between E-selectin and MBE (per 1-standard deviation increase; OR, 1.988; 95% CI, 1.379−2.866, p = 0.001) when the E-selectin levels were analyzed as a continuous variable. Furthermore, the restricted cubic spline demonstrated a linear correlation between serum E-selectin levels and the risk of MBE (p < 0.001 for linearity). Conclusions: In this prospective study, circulating levels of E-selectin were associated with an increased risk of MBE after EVT. Further mechanistic studies are warranted to elucidate the pathophysiology underlying this association. Full article

Recent studies have shown that neuropeptides and neurotrophic factors may be involved in the pathophysiological mechanisms of suicide. However, the current research on this aspect is still insufficient. Our study aimed to explore the biological patterns of suicide deaths, including levels of BDNF, proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2. The researchers selected 25 normal control patients matched by age with 30 suicide deaths. We used enzyme-linked immunosorbent assays to detect the levels of BDNF, proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2 in the plasma of suicide and control subjects. proBDNF, BDNF/proBDNF, Trk-b, GDNF, and TPH2 levels are shown as the median (25th–75th percentile). BDNF levels are shown as the mean (standard error of the mean). (1) The levels of plasma TPH2 and proBDNF in people who died by suicide were significantly higher than those in the control group. (2) The plasma levels of GDNF and BDNF/proBDNF in the suicide group were obviously lower than those in the control group. (3) There was no significant difference in plasma BDNF or Trk-b concentrations between the suicide group and the control group.Plasma TPH2, GDNF, and proBDNF levels are related to suicide. Plasma neurotrophic factor markers may predict suicide risk. Full article

Introduction: Post-Coronavirus disease 2019 (Post-COVID-19) syndrome has neurological symptoms related to the dysfunction of the autonomous nerve system. However, a pathogenic relationship between post-COVID-19 syndrome and dysautonomia still remains to be demonstrated. Establishing a pathogenic relationship between paresthesia and the presence of cardiac dysautonomia in patients with post-COVID-19 syndrome is the objective of this study. Participants and Methods: This observational study was carried out in the neurophysiology service wing of the Juan Bruno Zayas Hospital, Santiago de Cuba, in Cuba. The patients were recruited through a post-COVID-19 clinic at the same hospital. A variability study of cardiac frequency and a test of autonomic cardiovascular reflexes was carried out, which is composed of deep breathing, orthostatism, and the Valsalva maneuver. Results: The variability parameters of the cardiac frequency, the expiration–inspiration ratio between deep breaths, and the Valsalva Index showed no statistically significant differences between healthy participants and those with post-COVID-19 syndrome. During the Valsalva maneuver, there was a greater cardiac frequency response in participants with post-COVID-19 syndrome than in healthy subjects. The difference in supine and standing blood pressure was significantly minor in patients with post-COVID-19 syndrome. The logarithm of high frequency (log HF) increased significantly in patients with paresthesia when compared to patients without paresthesia. Conclusions: In the autonomic function tests, no signs of dysautonomia were found in patients with post-COVID-19 syndrome. The presence of paresthesias is associated with differences in cardiac vagal activity, which may suggest that damage to peripheral sensory nerve fibers could be associated with an affectation to autonomic fibres. Full article

Vascular cognitive impairment encompasses several types of deficits, ranging from mild cognitive impairment to dementia. Cognitive reserve refers to the brain’s ability to balance damage and improve performance through certain types of brain networks. The purpose of this review was to assess the relationship between reserve in vascular impairment, specifically looking at whether cognitive impairment is influenced by cognitive reserve, identifying significant vascular risk factors and their pathological pathways. To achieve this purpose, a review covering these issues was conducted within the Embase, Cochrane, and PubMed database. A total of 657 scientific articles were found, and 33 papers were considered for the final analysis. We concluded that there is no consensus on the protective effects of brain reserve on cognitive impairment. Stroke and diabetes can be considered significant risk factors for vascular cognitive impairment, while hypertension is not as damaging as blood pressure variability, which structurally alters the brain through a variety of mechanisms. Full article

One of the components of a dementia diagnosis is the assessment of functional abilities. These abilities are measured via screeners, such as the Instrumental Activities of Daily Living (IADL) scale. The IADL scale is a valid tool that has been adapted in many languages. This study aimed to provide a cut-off point and validate the Greek version of the IADL scale in populations with cognitive impairment. IADL data were collected from 132 individuals: 24 PD patients, 24 Parkinson’s disease dementia (PDD) patients, and 24 AD patients. The remaining 60 participants were cognitive healthy adults (CHAs). The CHA group and the PD group served as the cognitively unimpaired group (CUG), while the PDD and AD groups served as the cognitively impaired group (CIG). Additionally, the MMSE, the AMTS, the Clock Drawing Test CDT, the Arizona Battery for Communication Disorders of Dementia (ABCD), the NPI, and the GDS-15 were administered to the participants. Statistically significant differences in the IADL scores were exhibited between all subgroups. The IADL scale showed high internal consistency (Cronbach’s alpha = 0.890). A threshold equal to 6.00 (AUC = 0.888, p < 0.001) was estimated between the CUG and the CIG. Significant positive correlations were observed between IADL and MMSE (r = 0.764, p < 0.001), IADL and AMTS (r = 0.724, p < 0.001), IADL and ABCD (r = 0.702, p < 0.001), and IADL and CDT (r = 0.627, p < 0.001) results. Given the obtained results, the IADL scale is a valid tool for clinical use with high reliability and sensitivity. Also, the IADL scale is a valuable instrument for screening functional abilities associated with cognitive impairment. Full article

Multiple Sclerosis (MS) is a prevalent inflammatory disease in which the immune system plays an essential role in the damage, inflammation, and demyelination of central nervous system neurons (CNS). The cannabinoid receptor type 2 (CB₂) agonists possess anti-inflammatory effects against noxious stimuli and elevate the neuronal survival rate. We attempted to analyze the protective impact of low doses of β-Caryophyllene (BCP) in experimental autoimmune encephalomyelitis (EAE) mice as a chronic MS model. Immunization of female C57BL/6 mice was achieved through two subcutaneous injections into different areas of the hind flank with an emulsion that consisted of myelin Myelin oligodendrocyte glycoprotein (MOG)_35–55 (150 µg) and complete Freund’s adjuvant (CFA) (400 µg) with an equal volume. Two intraperitoneal (i.p.) injections of pertussis toxin (300 ng) were performed on the animals on day zero (immunizations day) and 48 h (2nd day) after injection of MOG + CFA. The defensive effect of low doses of BCP (2.5 and 5 mg/kg/d) was investigated in the presence and absence of a CB₂ receptor antagonist (1 mg/kg, AM630) in the EAE model. We also examined the pro/anti-inflammatory cytokine levels and the polarization of brain microglia and spleen lymphocytes in EAE animals. According to our findings, low doses of BCP offered protective impacts in the EAE mice treatment in a CB2 receptor-dependent way. In addition, according to results, BCP decreased the pathological and clinical defects in EAE mice via modulating adaptive (lymphocytes) and innate (microglia) immune systems from inflammatory phenotypes (M₁/Th₁/Th₁₇) to anti-inflammatory (M₂/Th₂/T_reg) phenotypes. Additionally, BCP elevated the anti-inflammatory cytokine IL-10 and reduced blood inflammatory cytokines. BCP almost targeted the systemic immune system more than the CNS immune system. Thus, a low dose of BCP can be suggested as a therapeutic effect on MS treatment with potent anti-inflammatory effects and possibly lower toxicity. Full article