Feature Papers in Neurosci

Pilocytic astrocytomas (PCA) are WHO Grade I tumors with a favorable prognosis. Surgical resection is usually curative. Nonetheless, progressive and/or metastatic disease occurs in 20% of patients. For these patients, treatment options are limited. The role of the immune system in PCA has not previously been reported. We hypothesize that the circulating cytokines contribute to tumorigenicity in PCA. This is an exploratory study with a focus on the identification of circulating cerebrospinal (CSF) cytokines associated with PCA. The primary objective is to demonstrate that CSF cytokines will be differentially expressed in the subset of PCAs that are difficult to treat in comparison to their surgically amendable counterparts. This is a single-institution, retrospective study of prospectively collected data. Patients with a confirmed histological diagnosis of PCA who have simultaneous intraoperative CSF sampling are included. Cerebrospinal fluid samples are subjected to multiplex cytokine profiling. Patient-derived PCA lines from selected patients in the same study cohort are cultured. Their cell culture supernatants are collected and interrogated using the sample multiplex platform as the CSF. A total of 8 patients are recruited. There were two patients with surgically difficult tumors associated with leptomeningeal involvement. Multiplex profiling of the cohort’s CSF samples showed elevated expressions of IFN-γ, IL-2, IL-12p70, IL-1β, IL-4, and TNF-α in these two patients in comparison to the remaining cohort. Next, primary cell lines derived from the same PCA patients demonstrated a similar trend of differential cytokine expression in their cell culture supernatant in vitro. Although our findings are preliminary at this stage, this is the first study in pediatric PCAs that show cytokine expression differences between the two groups of PCA with different clinical behaviors. Full article

Much work has been done to characterize domain-specific brain networks associated with reading, but very little work has been done with respect to spelling. Our aim was to characterize domain-specific spelling networks (SpNs) and domain-general resting state networks (RSNs) in adults with and without literacy impairments. Skilled and impaired adults were recruited from the University of Alberta. Participants completed three conditions of an in-scanner spelling task called a letter probe task (LPT). We found highly connected SpNs for both groups of individuals, albeit comparatively more connections for skilled (50) vs. impaired (43) readers. Notably, the SpNs did not correlate with spelling behaviour for either group. We also found relationships between SpNs and RSNs for both groups of individuals, this time with comparatively fewer connections for skilled (36) vs. impaired (53) readers. Finally, the RSNs did predict spelling performance in a limited manner for the skilled readers. These results advance our understanding of brain networks associated with spelling and add to the growing body of literature that describes the important and intricate connections between domain-specific networks and domain-general networks (i.e., resting states) in individuals with and without developmental disorders. Full article

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal, and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vessel-enriched and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in tight junction protein expression, serum albumin signals and astrocyte activation, i.e., increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively. Full article

Neuroscience is a vast discipline that deals with the anatomy, biochemistry, molecular biology, physiology and pathophysiology of central and peripheral nerves. Advances made through basic, translational, and clinical research in the field of neuroscience have great potential for long-lasting and beneficial impacts on human and animal health. The emerging field of biological therapy is intersecting with the disciplines of neuroscience, orthopaedics and rheumatology, creating new horizons for interdisciplinary and applied research. Biological drugs, growth factors, therapeutic peptides and monoclonal antibodies are being developed and tested for the treatment of painful arthritic and rheumatic diseases. This concise communication focuses on the solutions provided by the fields of neuroscience and neuroimmunology for real-world clinical problems in the field of orthopaedics and rheumatology, focusing on synovial joint pain and the emerging biological treatments that specifically target pathways implicated in osteoarthritis pain in peripheral nerves. Full article

In rats, some parvocellular paraventricular neurons project to spinal autonomic centers. Using the virus tracing technique, we have demonstrated that some magnocellular paraventricular neurons, but not supraoptic neurons, also project to autonomic preganglionic centers of the mammary gland, gingiva, or lip. A part of these neurons has shown oxytocin immunoreactivity. In the present experiment, we have examined whether the same magnocellular neuron that sends fibers to the retina or autonomic preganglionic centers of the eye also projects to the posterior pituitary. Double neurotropic viral labeling and oxytocin immunohistochemistry were used. After inoculation of the posterior pituitary and the eye with viruses, spreading in a retrograde direction and expressing different fluorescence proteins, we looked for double-labeled neurons in paraventricular and supraoptic nuclei. Double-labeled neurons were observed in non-sympathectomized and cervical-sympathectomized animals. Some double-labeled neurons contained oxytocin. After the optic nerve was cut, the labeling did not appear in the supraoptic nucleus; however, it could still be observed in the paraventricular nucleus. In the paraventricular nucleus, the double-labeled cells may be the origin of centrifugal visual fibers or autonomic premotor neurons. In the supraoptic nucleus, all double-labeled neurons are cells of origin of centrifugal visual fibers. Full article

Introduction and Purpose: Cerebral amyloid angiopathy (CAA) can be observed in patients with progressive supranuclear palsy (PSP), though to a lesser degree than in Alzheimer’s disease. The present post-mortem 7.0-tesla magnetic resonance imaging (MRI) evaluates whether CAA has an influence on the degree of hippocampal atrophy (HA) and on the incidence of associated micro-infarcts (HMIs) and cortical micro-bleeds (HMBs). Material and Methods: Eight brains with PSP-CAA were compared to 20 PSP brains without CAA. In addition to the neuropathological examination, the hippocampus was evaluated on the most representative coronal section with T2 and T2*-weighted MRI sequences. The average degree of HA was determined in both groups. The incidence of HMIs and HMBs was also compared as well as the frequency of cortical micro-infarcts (CoMIs) and cortical micro-bleeds (CoMBs) in the hemispheric neocortex. Results: The neuropathological examination showed a higher incidence of lacunar infarcts in the PSP-CAA brains compared to the PSP ones. With magnetic resonance imaging (MRI), the severity of HA and the incidence of HMIs and HMBs was similar between both groups. Additionally, the frequency of CoMIs and CoMBs in the neocortex was comparable. Conclusions: The association of CAA in PSP brains has no influence on the degree of HA and on the incidence of the small cerebrovascular lesions in the hippocampus as well as in the neocortex. Full article

Depolarization block is such a mechanism that the firing activity of a neuronal system is stopped for particular values of the input current. It is important to block epilepsy or unpleasant firing rates. We investigate this property for a non-linear model of CA3 hippocampal neurons under the action of endocannabinoid transmitters. The aim is to discover if they induce depolarization block, a property already seen in other neuronal models and observed in some experiments, signifying that the neural population increases its spiking frequency as some main parameter changes until reaching a situation of no firing. The results is theoretical and it could be useful for investigating real system of neurons of the hippocampus. In some papers it has been shown that this property is connected with bistability, which means that the system has two equilibrium states for some ranges of its parameters. Endocannabinoids influence the learning and memory process and so we concentrate our attention on the CA3 neurons of the hippocampus. We find bistability and depolarization block for the considered model, which is a generalization of the Wilson-Cowan model. The model describes average properties of neurons divided in three classes: the excitatory neuronal population (CA3 neurons) and two types of inhibitory neuron populations (basket cells). The exogenous concentration of cannabinoids is the parameter that controls bistability. This result can be used for an experiment that could give information for medical therapy. We study the time evolution of the synapses connecting the excitatory population with two types of basket cells. The evolution of synaptic weights is considered to be a toy model of the learning process. But this model cannot encompass the complexity and diversity of exogenous and endogenous endocannabinoids effects in vivo. Full article

Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition characterized by the abrupt, dramatic onset of obsessive–compulsive disorder (OCD) or eating restriction accompanied by equally abrupt and severe comorbid neuropsychiatric symptoms. PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection) is a heterogeneous syndrome identified as post-Streptococcus pyogenes infection (β-hemolytic Streptococcus group A) complications regarding the central nervous system with specific involvement of neuropsychiatric and behavioral skills. In the first part of our study, we share our experience in the treatment of a group of extreme-grade (according to CY-BOCS severity scale) symptomatic patients with intravenous immunoglobulin (IVIG), following the most recent studies regarding the dosage of the drug. Our contribution is to share our experience made on a sample of 55 patients all in the highest level of a severity grade. In the second part of our study, we also analyze the literature on PANS/PANDAS rehabilitation therapy, since in the literature there is no discussion of union and comparison on this method. Objective: This study aims to evaluate the clinical features of the patients observed from different Italian cohorts, with the attempt at evaluating clinical response to IVIG treatment in children with an extreme severity grade of PANS/PANDAS disease. Furthermore, after having analyzed the literature, we propose rehabilitation therapy as an added value to the pharmacological treatment. Materials and Methods: A total of 55 patients with a diagnosis of PANS/PANDAS, who belonged to an extreme grade of disease, were enrolled. All patients were administered with IVIG treatment at 2 g/kg per day for two consecutive days. Results: From our study, a noticeable improvement (until complete remission) of symptoms was evident for at least one year in 47 out of 55 (85%) observed children, while 11 out of these 43 (25%) showed an evident symptoms remission in a single attempt and the remaining 32 (75%) required a second administration to notice a lasting symptomatic improvement. Full article

Increased motivation towards alcohol use and suboptimal behavioral control are suggested to predispose adolescents to alcohol use disorders (AUDs). Paradoxically however, most adolescent AUDs resolve over time without any formal intervention, suggesting adolescent resilience to AUDs. Importantly, studies directly comparing adolescent and adult alcohol use are largely missing. We therefore aimed to unravel the moderating role of age in the relation between alcohol use and motivational and control-related cognitive processes in 45 adolescent drinkers compared to 45 adults. We found that enhancement drinking motives and impulsivity related positively to alcohol use. Although enhancement drinking motives and impulsivity were higher in adolescents, the strength of the relation between these measures and alcohol use did not differ between age groups. None of the alcohol use-related motivational measures (i.e., craving, attentional bias, and approach bias) and behavioral control measures (i.e., interference control, risky decision making, and working-memory) were associated with alcohol use or differed between age groups. These findings support the role of impulsivity and affective sensitivity in adolescent drinking but question the moderating role of age therein. The current study contributes towards understanding the role of age in the relation between alcohol use and cognition. Full article

Statistical learning is an innate function in the brain and considered to be essential for producing and comprehending structured information such as music. Within the framework of statistical learning the brain has an ability to calculate the transitional probabilities of sequences such as speech and music, and to predict a future state using learned statistics. This paper computationally examines whether and how statistical learning and knowledge partially contributes to musical representation in jazz improvisation. The results represent the time-course variations in a musician’s statistical knowledge. Furthermore, the findings show that improvisational musical representation might be susceptible to higher- but not lower-order statistical knowledge (i.e., knowledge of higher-order transitional probability). The evidence also demonstrates the individuality of improvisation for each improviser, which in part depends on statistical knowledge. Thus, this study suggests that statistical properties in jazz improvisation underline individuality of musical representation. Full article

The exact mechanism of action of different modifying treatments in the evolutionary course of multiple sclerosis (MS) remains unknown, but it is assumed that they act upon the cells involved in acquired immunity. One effect of these treatments is the development of lymphopenia, which carries inherent safety risks. This study was conducted to understand the alterations that teriflunomide (TERI) and dimethyl fumarate (DMF) exert upon white blood cells in a series of patients with MS. This study included a total of 99 patients; 44 treated with DMF and 55 patients treated with TERI. Blood counts were evaluated at baseline and every 6 months in order to track the absolute leukocyte, lymphocyte, and neutrophil counts. Twelve months after starting treatment, we observed a significant decrease in leukocytes (21.1%), lymphocytes (39.1%), and neutrophils (10%) in the DMF group. In the TERI group, leukocytes decreased by 11.1%, lymphocytes by 8.1%, and neutrophils by 15.7%. Both TERI and DMF produced a significant decrease in leukocytes during the first year of treatment and this was mainly related with a decrease in neutrophils in the TERI group and a decrease in lymphocytes in the DMF group. Full article

The main goal of this review is to summarize and discuss (1) age-dependent structural reorganization of mammalian visual cortical circuits underlying complex visual behavior functions in primary visual cortex (V1) and multiple extrastriate visual areas, and (2) current evidence supporting the notion of compensatory mechanisms in aged visual circuits as well as the use of rehabilitative therapy for the recovery of neural plasticity in normal and diseased aging visual circuit mechanisms in different species. It is well known that aging significantly modulates both the structural and physiological properties of visual cortical neurons in V1 and other visual cortical areas in various species. Compensatory aged neural mechanisms correlate with the complexity of visual functions; however, they do not always result in major circuit alterations resulting in age-dependent decline in performance of a visual task or neurodegenerative disorders. Computational load and neural processing gradually increase with age, and the complexity of compensatory mechanisms correlates with the intricacy of higher form visual perceptions that are more evident in higher-order visual areas. It is particularly interesting to note that the visual perceptual processing of certain visual behavior functions does not change with age. This review aims to comprehensively discuss the effect of normal aging on neuroanatomical alterations that underlie critical visual functions and more importantly to highlight differences between compensatory mechanisms in aged neural circuits and neural processes related to visual disorders. This type of approach will further enhance our understanding of inter-areal and cortico-cortical connectivity of visual circuits in normal aging and identify major circuit alterations that occur in different visual deficits, thus facilitating the design and evaluation of potential rehabilitation therapies as well as the assessment of the extent of their rejuvenation. Full article