Brain Sci., Volume 10, Issue 8 (August 2020) – 98 articles

A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions. Full article

Background. Craniofacial anomalies and minor neurological dysfunction (MNDs) have been identified, in literature, as risk factors for neurodevelopmental disorders. They represent physical indicators of embryonic development suggesting a possible contributory role of complications during early, even pre-conceptional, phases of ontogeny in autism spectrum disorders (ASD). Limited research has been conducted about the co-occurrence of the two biomarkers in children with ASD. This study investigates the associative patterns of cranio-facial anomalies and MNDs in ASD children, and whether these neurodevelopmental markers correlate with intensity of ASD symptoms and overall functioning. Methods. Caucasian children with ASD (n = 33) were examined. Measures were based on five anthropometric cranio-facial indexes and a standardized and detailed neurological examination according to Touwen. Relationships between anthropometric z-scores, MNDs and participant characteristics (i.e., age, cognitive abilities, severity of autistic symptoms measured using the Childhood Autism Rating Scale (CARS) checklist) were assessed. Results. With respect to specific MNDs, significant positive correlations were found between Cephalic Index and Sensory deficits (p-value < 0.001), which did not correlate with CARS score. Importantly, CARS score was positively linked with Intercanthal Index (p-value < 0.001), and negatively associated with posture and muscle tone (p-value = 0.027) and Facial Index (p-value = 0.004). Conclusion. Our data show a link between a specific facial phenotype and anomalies in motor responses, suggesting early brain dysmaturation involving subcortical structures in cerebro-craniofacial development of autistic children. This research supports the concept of a “social brain functional morphology” in autism spectrum disorders. Full article

Thiamine deficiency (TD) has detrimental effects on brain health and neurobehavioral development, and it is associated with many aging-related neurological disorders. To facilitate TD-related neuropsychological studies, we generated a TD mouse model by feeding a thiamine-deficient diet for 30 days, followed by re-feeding the control diet for either one week or 16 weeks as recovery treatment. We then performed neurobehavioral tests in these two cohorts: cohort of one week post TD treatment (1 wk-PTDT) and 16 weeks post TD treatment (16 wks-PTDT). The TD mice showed no significant difference from control in any tests in the 1 wk-PTDT cohort at the age of 13–14 weeks. The tests for the 16 wks-PTDT cohort at the age of 28–29 weeks, however, demonstrated anxiety and reduced locomotion in TD animals in open field and elevated plus maze. In comparison, rotor rod and water maze revealed no differences between TD and control mice. The current findings of the differential effects of the same TD treatment on locomotion and anxiety at different ages may reflect the progressive and moderate change of TD-induced neurobehavioral effects. The study suggests that, even though the immediate neurobehavioral impact of TD is modest or negligible at a young age, the impact could develop and become severe during the aging process. Full article

Anxiety disorders are prevalent and highly disabling mental disorders. In recent years, intensive efforts focused on the search for potential neuroimaging, genetic, and peripheral biomarkers in order to better understand the pathophysiology of these disorders, support their diagnosis, and characterize the treatment response. Of note, peripheral blood biomarkers, as surrogates for the central nervous system, represent a promising instrument to characterize psychiatric disorders, although their role has not been extensively applied to clinical practice. In this report, the state of the art on peripheral biomarkers of DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) Anxiety Disorders is presented, in order to examine their role in the pathogenesis of these conditions and their potential application for diagnosis and treatment. Available data on the cerebrospinal fluid and blood-based biomarkers related to neurotransmitters, neuropeptides, the hypothalamic–pituitary–adrenal axis, neurotrophic factors, and the inflammation and immune system are reviewed. Despite the wide scientific literature and the promising results in the field, only a few of the proposed peripheral biomarkers have been defined as a specific diagnostic instrument or have been identified as a guide in the treatment response to DSM-5 Anxiety Disorders. Therefore, further investigations are needed to provide new biological insights into the pathogenesis of anxiety disorders, to help in their diagnosis, and to tailor a treatment. Full article

Chronic kidney disease and Alzheimer’s disease are chronic conditions highly prevalent in elderly communities and societies, and a diagnosis of them is devastating and life changing. Demanding therapies and changes, such as non-compliance, cognitive impairment, and non-cognitive anomalies, may lead to supplementary symptoms and subsequent worsening of well-being and quality of life, impacting the socio-economic status of both patient and family. In recent decades, additional hypotheses have attempted to clarify the connection between these two diseases, multifactorial in their nature, but even so, the mechanisms behind this link are still elusive. In this paper, we sought to highlight the current understanding of the mechanisms for cognitive decline in patients with these concurrent pathologies and provide insight into the relationship between markers related to these disease entities and whether the potential biomarkers for renal function may be used for the diagnosis of Alzheimer’s disease. Exploring detailed knowledge of etiologies, heterogeneity of risk factors, and neuropathological processes associated with these conditions opens opportunities for the development of new therapies and biomarkers to delay or slow their progression and validation of whether the setting of chronic kidney disease could be a potential determinant for cognitive damage in Alzheimer’s disease. Full article

Structural changes in the hippocampus and amygdala have been demonstrated in schizophrenia patients. However, whether morphological information from these subcortical regions could be used by machine learning algorithms for schizophrenia classification were unknown. The aim of this study was to use volume of the amygdaloid and hippocampal subregions for schizophrenia classification. The dataset consisted of 57 patients with schizophrenia and 69 healthy controls. The volume of 26 hippocampal and 20 amygdaloid subregions were extracted from T1 structural MRI images. Sequential backward elimination (SBE) algorithm was used for feature selection, and a linear support vector machine (SVM) classifier was configured to explore the feasibility of hippocampal and amygdaloid subregions in the classification of schizophrenia. The proposed SBE-SVM model achieved a classification accuracy of 81.75% on 57 patients and 69 healthy controls, with a sensitivity of 84.21% and a specificity of 81.16%. AUC was 0.8241 (p < 0.001 tested with 1000-times permutation). The results demonstrated evidence of hippocampal and amygdaloid structural changes in schizophrenia patients, and also suggested that morphological features from the amygdaloid and hippocampal subregions could be used by machine learning algorithms for the classification of schizophrenia. Full article

Intradural spinal arteriovenous fistulas (sAVF) are spinal vascular lesions that usually manifest due to myelopathy or local symptoms caused by venous congestion and ischemia. In addition, perimedullary arteriovenous fistulas (PMAVF) in particular may rupture and cause subarachnoid or intramedullary hemorrhage along with relevant symptoms. Subarachnoid hemorrhage (SAH) can propagate into cranial space with clinically dominant symptoms and signs of typical aneurysmal intracranial SAH. The standard workup for cerebral SAH, after excluding an intracranial source of hemorrhage, is usually limited to a cervical spine MRI; therefore, thoracolumbar sources of hemorrhage can be missed, or their diagnosis may be delayed. Here we present a case of a pregnant patient who presented with cerebral SAH. The source of hemorrhage was not initially identified, leading to a presumptive diagnosis of benign pretruncal non-aneurysmal SAH. The correct diagnosis of spinal thoracolumbar PMAVF was revealed 2.5 months later due to the progression of local symptoms. While the diagnosis was being refined and endovascular treatment was being planned (but delayed due to pregnancy), there was a recurrence of intraconal hemorrhage followed by brainstem hemorrhage. This led to significant clinical deterioration. The PMAVF was then treated microsurgically and the patient experienced partial recovery. Full article

Background: Recent studies have demonstrated that brain activities using NIRS (near-infrared spectroscopy) at baseline during cognitive tasks (e.g., N-back task) can predict the cognitive benefits of a cognitive training. In this study, we investigated whether brain activities during brain training game (BT) at baseline would predict benefits to cognitive functions after the intervention period. Methods: In a four-week double-blinded randomized control trial (RCT) 72 young adults were randomly assigned to one of the two groups: participants in the BT group played specific game, called the Brain Age. Participants in an active control group (ACT) played the puzzle game Tetris. We measured brain activity during the training games using two channel NIRS before the intervention period. Cognitive functions were tested before and after the four-week intervention period. Results: The BT showed significant improvements in inhibition, processing speed, and working memory performance compared to ACT. The left and right DLPFC (dorsolateral prefrontal cortex) brain activities during the BT at baseline were associated with improvements in inhibition and processing speed. Discussion: This randomized control trial first provides scientific evidence that DLPFC activities during BT at baseline can predict cognitive improvements after a four-week intervention period. Full article

Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells. Full article

Dyslexia is a specific disorder in reading abilities. The aim of this study was to explore whether a short visual attentional training could improve reading capabilities in children with reading disorders by changing their oculomotor characteristics. Two groups (G1 and G2) of 25 children with reading disabilities and who are matched in IQ (intelligence quotient), sex, and age participated in the study. The allocation of a subject to a specific group (G1 = experimental group; G2 = control group) was generated in an unpredictable random sequence. The reading task was recorded twice for G1, i.e., before (T1) and after (T2) 10 min of visual attentional training. Training consisted of oculomotor tasks (saccades and pursuits movements) and searching tasks (three different exercises). For G2, the two reading tasks at T1 and T2 were done at an interval of 10 min instead. We found that at T1, oculomotor performances during reading were statistically similar for both groups of children with reading disabilities (G1 and G2). At T2, the group G1 only improved oculomotor capabilities significantly during reading; in particular, children read faster, and their fixation time was shortest. We conclude that short visual attentional training could improve the cortical mechanisms responsible for attention and reading capabilities. Further studies on a larger number of dyslexic children will be necessary in order to explore the effects of different training types on the visual attentional span given its important role on the orienting and focusing visuospatial attention and on the oculomotor performance in children with dyslexia. Full article

Background: There has been a considerable endeavor to understand associated challenges of caregiving for a child with Autism Spectrum Disorders (ASDs) and to develop the necessary skills and approaches to assist parents of children with ASD. Different studies have been stressed the importance and need for parental involvement in the intervention process to increase positive impacts. Methods: The process of caregiving and the associated challenges should be understood from different aspects to be able to facilitate parent involvement in intervention implementation. In a narrative literature review, ten selected reviews were considered and each review considered a special aspect of caregiving for an individual with ASD. Results: Five main different factors in the available literature and reviews were considered as different themes that needed to be reconsidered in the studies on the impacts of caregiving for an individual with ASD. Conclusions: It is concluded that to facilitate parental involvement in the intervention process, and to support caregivers of this group of individuals this review highlights the need for improved research in some proposed areas in this field and to bridge the gap between research and practice in this field. Full article

Healthy aging is associated with decline in the ability to maintain visual information in working memory (WM). We examined whether this decline can be explained by decreases in the ability to filter distraction during encoding or to ignore distraction during memory maintenance. Distraction consisted of irrelevant objects (Exp. 1) or irrelevant features of an object (Exp. 2). In Experiment 1, participants completed a spatial WM task requiring remembering locations on a grid. During encoding or during maintenance, irrelevant distractor positions were presented. In Experiment 2, participants encoded either single-feature (colors or orientations) or multifeature objects (colored triangles) and later reproduced one of these features using a continuous scale. In multifeature blocks, a precue appeared before encoding or a retrocue appeared during memory maintenance indicating with 100% certainty to the to-be-tested feature, thereby enabling filtering and ignoring of the irrelevant (not-cued) feature, respectively. There were no age-related deficits in the efficiency of filtering and ignoring distractor objects (Exp. 1) and of filtering irrelevant features (Exp. 2). Both younger and older adults could not ignore irrelevant features when cued with a retrocue. Overall, our results provide no evidence for an aging deficit in using attention to manage visual WM. Full article

(1) Objective: The objective was two-fold: (a) test a protocol of combined interventions; (b) administer this combined protocol within the framework of a six-month, intensive, long-duration program. The array of interventions was designed to target the treatment-resistant impairments underlying persistent mobility dysfunction: weakness, balance deficit, limb movement dyscoordination, and gait dyscoordination. (2) Methods: A convenience sample of eight chronic stroke survivors (>4 months post stroke) was enrolled. Treatment was 5 days/week, 1–2.5 h/day for 6 months, as follows: strengthening exercise, balance training, limb/gait coordination training, and aerobic exercise. Outcome measures: Berg Balance Scale (BBS), Fugl-Meyer Lower Limb Coordination (FM), gait speed, 6 Minute Walk Test (6MWT), Timed up and Go (TUG), Functional Independence Measure (FIM), Craig Handicap Assessment Rating Tool (CHART), and personal milestones. Pre-/post-treatment comparisons were conducted using the Permutation Test, suitable for ordinal measures and small sample size. (3) Results: For the group, there was a statistically (p ≤ 0.04) significant improvement in balance, limb movement coordination (FM), gait speed, functional mobility (TUG), and functional activities (FIM). There were measurable differences (minimum detectible change: MDC) in BBS, FM, gait speed, 6MWT, and TUG. There were clinically significant milestones achieved for selected subjects according to clinical benchmarks for the BBS, 6MWT, gait speed, and TUG, as well as achievement of personal milestones of life role participation. Effect sizes (Cohen’s D) ranged from 0.5 to 1.0 (with the exception of the (6MWT)). After six months of treatment, the above array of gains were beyond that reported by other published studies of chronic stroke survivor interventions. Personal milestones included: walking to mailbox, gardening/yardwork, walking a distance to neighbors, return to driving, membership at a fitness center, vacation trip to the beach, swimming at local pool, returning to work, housework, cooking meals. (4) Conclusions: Stroke survivors with mobility dysfunction were able to participate in the long-duration, intensive program, with the intervention array targeted to address impairments underlying mobility dysfunction. There were either clinically or statistically significant improvements in an array of measures of impairment, functional mobility, and personal milestone achievements. Full article

Dural arteriovenous fistulas involving the cavernous sinus can lead to orbital pain, vision loss and, in the setting of associated cortical venous reflux, intracranial hemorrhage. The treatment of dural arteriovenous fistulas has primarily become the role of the endovascular surgeon. The venous anatomy surrounding the cavernous sinus and venous sinus thrombosis that is often associated with these fistulas contributes to the complexity of these interventions. The current report gives a detailed description of the alternate endovascular routes to the cavernous sinus based on a single center’s experience as well as a literature review supporting each approach. A comprehensive understanding of the anatomy and approaches to the cavernous sinus available to the endovascular surgeon is vital to the successful treatment of this condition. Full article

Brain tumours are a serious concern among both physicians and patients. The most feared brain tumour is glioblastoma (GBM) due to its heterogeneous histology, substantial invasive capacity, and rapid postsurgical recurrence. Even in cases of early management consisting of surgery, chemo-, and radiotherapy, the prognosis is still poor, with an extremely short survival period. Consequently, researchers are trying to better understand the underlying pathways involved in GBM development in order to establish a more personalised approach. The latest focus is on molecular characterisation of the tumour, including analysis of extracellular vesicles (EVs), nanostructures derived from both normal and pathological cells that have an important role in intercellular communication due to the various molecules they carry. There are two types of EV based on their biogenesis, but exosomes are of particular interest in GBM. Recent studies have demonstrated that GBM cells release numerous exosomes whose cargo provides them the capacity to facilitate tumour cell invasion and migration, to stimulate malignant transformation of previously normal cells, to increase immune tolerance towards the tumour, to induce resistance to chemotherapy, and to enhance the GBM vascular supply. As exosomes are specific to their parental cells, their isolation would allow a deeper perspective on GBM pathogenesis. A new era of molecular manipulation has emerged, and exosomes are rapidly proving their value not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting GBM cells. Nonetheless, further research will be required before exosomes could be used in clinical practice. This review aims to describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment. Full article

Traditionally, the medial temporal lobe has been considered a key brain region for spatial memory. Nevertheless, executive functions, such as working memory, also play an important role in complex behaviors, such as spatial navigation. Thus, the main goal of this study is to clarify the relationship between working memory capacity and spatial memory performance. Spatial memory was assessed using a virtual reality-based procedure, the Boxes Room task, and the visual working memory with the computer-based Change Localization Task. One hundred and twenty-three (n = 123) participants took part in this study. Analysis of Covariance (ANCOVA) revealed a statistically significant relationship between working memory capacity and spatial abilities. Thereafter, two subgroups n = 60, were formed according to their performance in the working memory task (1st and 4th quartiles, n = 30 each). Results demonstrate that participants with high working memory capacity committed fewer mistakes in the spatial task compared to the low working memory capacity group. Both groups improved their performance through repeated trials of the spatial task, thus showing that they could learn spatial layouts independent of their working memory capacity. In conclusion, these findings support that spatial memory performance is directly related to working memory skills. This could be relevant for spatial memory assessment in brain lesioned patients. Full article

Analysis of physiological signals, electroencephalography more specifically, is considered a very promising technique to obtain objective measures for mental workload evaluation, however, it requires a complex apparatus to record, and thus, with poor usability in monitoring in-vehicle drivers’ mental workload. This study proposes a methodology of constructing a novel mutual information-based feature set from the fusion of electroencephalography and vehicular signals acquired through a real driving experiment and deployed in evaluating drivers’ mental workload. Mutual information of electroencephalography and vehicular signals were used as the prime factor for the fusion of features. In order to assess the reliability of the developed feature set mental workload score prediction, classification and event classification tasks were performed using different machine learning models. Moreover, features extracted from electroencephalography were used to compare the performance. In the prediction of mental workload score, expert-defined scores were used as the target values. For classification tasks, true labels were set from contextual information of the experiment. An extensive evaluation of every prediction tasks was carried out using different validation methods. In predicting the mental workload score from the proposed feature set lowest mean absolute error was 0.09 and for classifying mental workload highest accuracy was 94%. According to the outcome of the study, it can be stated that the novel mutual information based features developed through the proposed approach can be employed to classify and monitor in-vehicle drivers’ mental workload. Full article

Early social-linguistic experience influences infants’ attention to faces but little is known about how infants attend to the faces of speakers engaging in conversation. Here, we examine how monolingual and bilingual infants attended to speakers during a conversation, and we tested for the possibility that infants’ visual attention may be modulated by familiarity with the language being spoken. We recorded eye movements in monolingual and bilingual 15-to-24-month-olds as they watched video clips of speakers using infant-directed speech while conversing in a familiar or unfamiliar language, with each other and to the infant. Overall, findings suggest that bilingual infants visually shift attention to a speaker prior to speech onset more when an unfamiliar, rather than a familiar, language is being spoken. However, this same effect was not found for monolingual infants. Thus, infants’ familiarity with the language being spoken, and perhaps their language experiences, may modulate infants’ visual attention to speakers. Full article

Asymmetrical lower limb strength is a significant contributor to impaired walking abilities in people with multiple sclerosis (PwMS). Transcranial direct current stimulation (tDCS) may be an effective technique to enhance cortical excitability and increase neural drive to more-affected lower limbs. A sham-controlled, randomized, cross-over design was employed. Two women with MS underwent two 20 min sessions of either 3 mA tDCS or Sham before 20 min of treadmill walking at a self-selected speed. During walking, the participants were injected with the glucose analogue, [¹⁸F] fluorodeoxyglucose (FDG). Participants were then imaged to examine glucose metabolism and uptake asymmetries in the legs. Standardized uptake values (SUVs) were compared between the legs and asymmetry indices were calculated. Subject 2 was considered physically active (self-reported participating in at least 30 min of moderate-intensity physical activity on at least three days of the week for the last three months), while Subject 1 was physically inactive. In Subject 1, there was a decrease in SUVs at the left knee flexors, left upper leg, left and right plantar flexors, and left and right lower legs and SUVs in the knee extensors and dorsiflexors were considered symmetric after tDCS compared to Sham. Subject 2 showed an increase in SUVs at the left and right upper legs, right plantar flexors, and right lower leg with no muscle group changing asymmetry status. This study demonstrates that tDCS may increase neural drive to leg muscles and decrease glucose uptake during walking in PwMS with low physical activity levels. Full article

Background: Cladribine (2-CdA) can cross the blood–brain barrier, resulting in inhibition of DNA synthesis and repair and disruption of cellular proliferation in actively dividing lymphocytes. No data on effect on neurons are available. Aim: To study “in vitro” 2-CdA apoptotic effects on neurons in healthy donor and multiple sclerosis patient lymphocytes. Methods: Neuroblastoma cells were co-cultured with lymphocytes, with and without 2-CdA. Results: Apoptosis increased in lymphocytes with 2-CdA; increase was also observed when lymphocytes were cultured with neuronal cells. However, neurons were not affected by 2-CdA for apoptosis. Conclusions: 2-CdA causes peripheral and central lymphocyte death preserving neurons, with a reasonable impact on inflammation and neuroprotection. Full article

Anodal transcranial direct current stimulation (tDCS) is a painless noninvasive method that reportedly improves cognitive function in Alzheimer’s disease (AD) by stimulating the brain. However, its underlying mechanism remains unclear. Thus, the present study investigates the cognitive effects in a 5xFAD AD mouse model using electrophysiological and pathological methods. We used male 5xFAD C57BL/6J and male C57BL/6J wild-type mice; the dementia model was confirmed through DNA sequencing. The verified AD and wild-type mice were randomly assigned into four groups of five mice each: an induced AD group receiving tDCS treatment (Stim-AD), an induced AD group not receiving tDCS (noStim-AD), a non-induction group receiving tDCS (Stim-WT), and a non-induction group not receiving tDCS (noStim-WT). In the Stim group, mice received tDCS in the frontal bregma areas at an intensity of 200 µA for 20 min. After 2 weeks of treatment, we decapitated the mice, removed the hippocampus from the brain, confirmed its neuronal activation through excitatory postsynaptic potential (EPSP) recording, and performed molecular experiments on the remaining tissue using western blots. EPSP significantly increased in the Stim-AD group compared to that in the noStim-AD, which was comparable to that in the non-induced groups, Stim-WT and noStim-WT. There were no significant differences in cyclic amp-response element binding protein (CREB), phosphorylated CREB (pCREB), and Brain-derived neurotrophic factor (BDNF) levels in the Stim-AD group compared to those in the noStim-AD group. This study demonstrated that a tDCS in both frontal lobes of a transgenic 5xFAD mouse model affects long-term potentiation, indicating possible enhancement of cognitive function. Full article

Background: Patients with Fabry’s disease (FD) may be asymptomatic or show a spectrum of clinical manifestations, including cerebrovascular disease, mainly affecting posterior circulation. Few and conflicting studies on cerebral blood flow (CBF) velocity by transcranial Doppler sonography (TCD) in asymptomatic FD (aFD) subjects have been published. Our study aims to assess TCD in aFD subjects to identify any preclinical CBF change. Methods: A total of 30 aFD subjects were consecutively recruited and compared to 28 healthy controls. Brain magnetic resonance imaging was normal in all participants. TCD was used to study blood flow velocity and indices of resistance of intracranial arteries from the middle cerebral artery (MCA), bilaterally, and from the basilar artery (BA). Cerebral vasomotor reactivity (CVR) was also evaluated from MCA. Results: No difference was found between groups for MCA parameters of CBF velocity and CVR. Compared to controls, a higher mean blood flow velocity and a lower resistance index from BA were observed in FD subjects. No correlation was found between any BA-derived TCD parameter and the level of lyso-globotriaosylceramide. Conclusions: aFD subjects show evidence of altered CBF velocity in posterior circulation. Preclinical detection of neurovascular involvement in FD might allow appropriate management and prevention of future cerebrovascular complications and disability. Full article

Valproic acid (VPA) is a multifunctional medication used for the treatment of epilepsy, mania associated with bipolar disorder, and migraine. The pharmacological effects of VPA involve a variety of neurotransmitter and cell signaling systems, but the molecular mechanisms underlying its clinical efficacy is to date largely unknown. In this study, we used the isobaric tags for relative and absolute quantitation shotgun proteomic analysis to screen differentially expressed proteins in VPA-treated SH-SY5Y cells. We identified changes in the expression levels of multiple proteins involved in Alzheimer’s disease, Parkinson’s disease, chromatin remodeling, controlling gene expression via the vitamin D receptor, ribosome biogenesis, ubiquitin-mediated proteolysis, and the mitochondrial oxidative phosphorylation and electron transport chain. Our data indicate that VPA may modulate the differential expression of proteins involved in mitochondrial function and vitamin D receptor-mediated chromatin transcriptional regulation and proteins implicated in the pathogenesis of neurodegenerative diseases. Full article

In this study, we investigated the associations between implicit associative learning with the cortisol and salivary alpha-amylase (sAA) stress response to an acute stressor as well as their associations with attention. Eighty one healthy adults (25 male) participated and either performed the socially evaluated cold-pressor test (SECPT) or a warm-water control task (WWT). Either prior to or immediately after the SECPT/WWT, participants implicitly learned digit-symbol pairs. A not-previously announced recall test was conducted about 20 min after the SECPT/WWT. Attention was assessed by means of a Stroop task at nine time points over the course of the experiment. Memory recall performance was not significantly associated with the acquisition time point (pre or post stressor) and did not significantly differ between the responder groups (i.e., non-responders, sAA-and-cortisol responders, only sAA responders, and only cortisol responders). Attentional performance increased throughout the experiment (i.e., reaction times in the Stroop task decreased). No differences in the attentional time course were found between the responder groups. However, some associations were found (p_uncorrected < 0.05) that did not pass the multiple comparison adjusted alpha level of α_adjusted = 0.002, indicating different associations between attention and implicit learning between the responder groups. We conclude that the associations of sAA and cortisol responses with implicit learning are complex and are related to each other. Further studies in which both (sAA and cortisol responses) are selectively (de-) activated are needed. Furthermore, different learning tasks and less—potentially stressful—attentional assessments should be used in future research. Moreover, field studies are needed in which the associations between acute stress and implicit associative learning are investigated in everyday life. Full article

Reports of behavioral disturbance in Juvenile-Onset Huntington’s Disease (JOHD) have been based primarily on qualitative caregiver reports or retrospective medical record reviews. This study aims to quantify differences in behavior in patients with JOHD using informant- and self-report questionnaires. Informants of 21 children/young adults (12 female) with JOHD and 115 children/young adults (64 female) with a family history of Huntington’s Disease, but who did not inherit the disease themselves (Gene-Non-Expanded; GNE) completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Pediatric Behavior Scale (PBS). Mixed linear regression models (age/sex adjusted) were conducted to assess group differences on these measures. The JOHD group had significantly higher scores, indicating more problems, than the GNE group on all BRIEF subscales, and measures of Aggression/Opposition and Hyperactivity/Inattention of the PBS (all p < 0.05). There were no group differences in Depression/Anxiety. Inhibit, Plan/Organize, Initiate, and Aggression/Opposition had significant negative correlations with Cytosine-Adenine-Guanine (CAG) repeat length (all p < 0.05) meaning that individuals with higher CAG repeats scored lower on these measures. There was greater discrepancy between higher informant-vs. lower self-reported scores in the JOHD group, supporting the notion of lack of insight for the JOHD-affected group. These results provide quantitative evidence of behavioral characteristics of JOHD. Full article

Visual working memory (VWM) resources have been shown to be flexibly distributed according to item priority. This flexible allocation of resources may depend on attentional control, an executive function known to decline with age. In this study, we sought to determine how age differences in attentional control affect VWM performance when attention is flexibly allocated amongst targets of varying priority. Participants performed a delayed-recall task wherein item priority was varied. Error was modelled using a three-component mixture model to probe different aspects of performance (precision, guess-rate, and non-target errors). The flexible resource model offered a good fit to the data from both age groups, but older adults showed consistently lower precision and higher guess rates. Importantly, when demands on flexible resource allocation were highest, older adults showed more non-target errors, often swapping in the item that had a higher priority at encoding. Taken together, these results suggest that the ability to flexibly allocate attention in VWM is largely maintained with age, but older adults are less precise overall and sometimes swap in salient, but no longer relevant, items possibly due to their lessened ability to inhibit previously attended information. Full article

Kava roots have been extensively studied in clinical trials as potential candidate anti-anxiety drugs. However, anti-convulsive properties of various tissues of stems of Kava have not been reported to date. The objective of the study was to evaluate the anti-convulsive potential of aqueous extracts prepared from specific tissues of Kava (Piper methysticum) stems in zebrafish, using the PTZ-induced seizure model. The potency of each extract was compared in terms of the intensity of seizure scores and onset time after pre-treating the zebrafish before the PTZ challenge. The results indicate that aqueous extract of Kava stems without peel after 45 min of pre-treatment exhibited anti-convulsive potential at the dose of 50 mg/L. This study provides evidence to the anti-convulsive properties of peeled Kava stems and its potential for investigation and design of candidate anti-convulsive drugs. Full article

Background: Visual hallucinations (VH) are a common symptom in dementia with Lewy bodies (DLB); however, their cognitive underpinnings remain unclear. Hallucinations have been related to cognitive slowing in DLB and may arise due to impaired sensory input, dysregulation in top-down influences over perception, or an imbalance between the two, resulting in false visual inferences. Methods: Here we employed a drift diffusion model yielding estimates of perceptual encoding time, decision threshold, and drift rate of evidence accumulation to (i) investigate the nature of DLB-related slowing of responses and (ii) their relationship to visuospatial performance and visual hallucinations. The EZ drift diffusion model was fitted to mean reaction time (RT), accuracy and RT variance from two-choice reaction time (CRT) tasks and data were compared between groups of mild cognitive impairment (MCI-LB) LB patients (n = 49) and healthy older adults (n = 25). Results: No difference was detected in drift rate between patients and controls, but MCI-LB patients showed slower non-decision times and boundary separation values than control participants. Furthermore, non-decision time was negatively correlated with visuospatial performance in MCI-LB, and score on visual hallucinations inventory. However, only boundary separation was related to clinical incidence of visual hallucinations. Conclusions: These results suggest that a primary impairment in perceptual encoding may contribute to the visuospatial performance, however a more cautious response strategy may be related to visual hallucinations in Lewy body disease. Interestingly, MCI-LB patients showed no impairment in information processing ability, suggesting that, when perceptual encoding was successful, patients were able to normally process information, potentially explaining the variability of hallucination incidence. Full article

(1) Introduction: Epiconus and conus medullary syndromes that consisted of drop foot, pain, numbness, bladder or bowel dysfunction are serious problems might be caused by lumbar disc(s) herniation (LDH) compression. (2) Objective: To evaluate percutaneous discectomy effectivity for decompressing LDH lesions. (3) Case Report: Three patients suffered from drop feet, numbness, and bowel and bladder problems due to LDH compression. Patient #1 is a male (35 years old, basal metabolism index (BMI) = 23.9), point 1 on manual muscle test (MMT), with protrusion on L3 to S1 discs; Patient #2 is a female (62 years old, BMI = 22.4), point 3 on MMT, with protrusion on L2-4 and L5-S1 discs; Patient #3 is a female (43 years old, BMI = 26.6), point 4 on MMT, with extrusion on T12-L1 and L1-2 and L3-4 protruded discs. Six months follow-up showed of stand and walkability improvement with Patient #1 and #2. Patient #3 showed improvement in bowel and bladder problems within 10 weeks, without suffering of postoperative pain syndromes. (4) Discussion: Patient #1 and #2 showed better outcomes than Patient #3 who affected epiconus and cauda equina syndromes. Triamcinolone and lidocaine have analgesic and anti-inflammatory properties for improving intraepidural circulation adjacent to the lesion sites. (5) Conclusion: Drop foot caused by mechanical compression of LDH ought to be treated immediately. Lateral or posterolateral compression has better outcomes associated with anatomical structures. Discectomy through transforaminal approach that is followed by caudal epidural steroid injection (CESI) under fluoroscopic guidance is a safer and minimally invasive treatment with promising outcomes. Full article

(1) Background: Distal aneurysms of cerebellar arteries are very rare. The authors report their case series of distal aneurysms of the cerebellar arteries solved successfully by microsurgery or by endovascular treatment (Table 1) (2) Materials and Methods: Between January 2010 and March 2020, 346 aneurysms were treated in our institution. Eleven aneurysms in seven patients were located on distal cerebellar arteries and, in three patients, the aneurysms were combined with arteriovenous malformations. There were four women and three men, ranging from 50 to 72 years of age. Five patients presented with different grades of subarachnoid hemorrhage or intraventricular bleeding, and two patients were diagnosed because of headache. Aneurysm location was the posterior inferior cerebellar artery in six cases, the superior cerebellar artery in three cases, and the anterior inferior cerebellar artery in 2 cases. One patient had three aneurysms, and two patients had two aneurysms. (3) Results: Nine aneurysms were treated by microsurgery trapping or clipping and, in two patients, the associated arteriovenous malformation (AVM) was resected. Two aneurysms were treated by endovascular coiling, and one associated AVM was successfully embolized. Clinical follow-up was a mean of 11.5 months (range, 3–45 months). (4) Conclusion: The authors present their experience with the treatment of 11 peripheral aneurysms on distal branches of the cerebellar circulation in seven patients which were excluded from circulation by microsurgery or endovascular treatment. In three patients, the associated AVM was treated (two with microsurgery, one with embolization). Full article