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Brain Sci., Volume 9, Issue 10 (October 2019)

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Cover Story (view full-size image) Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder characterized by deficits in [...] Read more.
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Open AccessArticle
Computer-Aided Diagnosis System of Alzheimer’s Disease Based on Multimodal Fusion: Tissue Quantification Based on the Hybrid Fuzzy-Genetic-Possibilistic Model and Discriminative Classification Based on the SVDD Model
Brain Sci. 2019, 9(10), 289; https://doi.org/10.3390/brainsci9100289 - 22 Oct 2019
Abstract
An improved computer-aided diagnosis (CAD) system is proposed for the early diagnosis of Alzheimer’s disease (AD) based on the fusion of anatomical (magnetic resonance imaging (MRI)) and functional (8F-fluorodeoxyglucose positron emission tomography (FDG-PET)) multimodal images, and which helps to address the [...] Read more.
An improved computer-aided diagnosis (CAD) system is proposed for the early diagnosis of Alzheimer’s disease (AD) based on the fusion of anatomical (magnetic resonance imaging (MRI)) and functional (8F-fluorodeoxyglucose positron emission tomography (FDG-PET)) multimodal images, and which helps to address the strong ambiguity or the uncertainty produced in brain images. The merit of this fusion is that it provides anatomical information for the accurate detection of pathological areas characterized in functional imaging by physiological abnormalities. First, quantification of brain tissue volumes is proposed based on a fusion scheme in three successive steps: modeling, fusion and decision. (1) Modeling which consists of three sub-steps: the initialization of the centroids of the tissue clusters by applying the Bias corrected Fuzzy C-Means (FCM) clustering algorithm. Then, the optimization of the initial partition is performed by running genetic algorithms. Finally, the creation of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF) tissue maps by applying the Possibilistic FCM clustering algorithm. (2) Fusion using a possibilistic operator to merge the maps of the MRI and PET images highlighting redundancies and managing ambiguities. (3) Decision offering more representative anatomo-functional fusion images. Second, a support vector data description (SVDD) classifier is used that must reliably distinguish AD from normal aging and automatically detects outliers. The “divide and conquer” strategy is then used, which speeds up the SVDD process and reduces the load and cost of the calculating. The robustness of the tissue quantification process is proven against noise (20% level), partial volume effects and when inhomogeneities of spatial intensity are high. Thus, the superiority of the SVDD classifier over competing conventional systems is also demonstrated with the adoption of the 10-fold cross-validation approach for synthetic datasets (Alzheimer disease neuroimaging (ADNI) and Open Access Series of Imaging Studies (OASIS)) and real images. The percentage of classification in terms of accuracy, sensitivity, specificity and area under ROC curve was 93.65%, 90.08%, 92.75% and 97.3%; 91.46%, 92%, 91.78% and 96.7%; 85.09%, 86.41%, 84.92% and 94.6% in the case of the ADNI, OASIS and real images respectively. Full article
(This article belongs to the Special Issue Biomarkers for Early Diagnosis of Dementia)
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Open AccessArticle
Integrated Analysis of microRNA and mRNA Expression Profiles: An Attempt to Disentangle the Complex Interaction Network in Attention Deficit Hyperactivity Disorder
Brain Sci. 2019, 9(10), 288; https://doi.org/10.3390/brainsci9100288 - 22 Oct 2019
Abstract
Attention Deficit Hyperactivity Disorder (ADHD) is a childhood-onset neurodevelopmental disorder, whose etiology and pathogenesis are still largely unknown. In order to uncover novel regulatory networks and molecular pathways possibly related to ADHD, we performed an integrated miRNA and mRNA expression profiling analysis in [...] Read more.
Attention Deficit Hyperactivity Disorder (ADHD) is a childhood-onset neurodevelopmental disorder, whose etiology and pathogenesis are still largely unknown. In order to uncover novel regulatory networks and molecular pathways possibly related to ADHD, we performed an integrated miRNA and mRNA expression profiling analysis in peripheral blood samples of children with ADHD and age-matched typically developing (TD) children. The expression levels of 13 miRNAs were evaluated with microfluidic qPCR, and differentially expressed (DE) mRNAs were detected on an Illumina HiSeq 2500 genome analyzer. The miRNA targetome was identified using an integrated approach of validated and predicted interaction data extracted from seven different bioinformatic tools. Gene Ontology (GO) and pathway enrichment analyses were carried out. Results showed that six miRNAs (miR-652-3p, miR-942-5p, let-7b-5p, miR-181a-5p, miR-320a, and miR-148b-3p) and 560 genes were significantly DE in children with ADHD compared to TD subjects. After correction for multiple testing, only three miRNAs (miR-652-3p, miR-148b-3p, and miR-942-5p) remained significant. Genes known to be associated with ADHD (e.g., B4GALT2, SLC6A9 TLE1, ANK3, TRIO, TAF1, and SYNE1) were confirmed to be significantly DE in our study. Integrated miRNA and mRNA expression data identified critical key hubs involved in ADHD. Finally, the GO and pathway enrichment analyses of all DE genes showed their deep involvement in immune functions, reinforcing the hypothesis that an immune imbalance might contribute to the ADHD etiology. Despite the relatively small sample size, in this study we were able to build a complex miRNA-target interaction network in children with ADHD that might help in deciphering the disease pathogenesis. Validation in larger samples should be performed in order to possibly suggest novel therapeutic strategies for treating this complex disease. Full article
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Open AccessArticle
Assessing the Effects of Cytoprotectants on Selective Neuronal Loss, Sensorimotor Deficit and Microglial Activation after Temporary Middle Cerebral Occlusion
Brain Sci. 2019, 9(10), 287; https://doi.org/10.3390/brainsci9100287 - 22 Oct 2019
Abstract
Although early reperfusion after stroke salvages the still-viable ischemic tissue, peri-infarct selective neuronal loss (SNL) can cause sensorimotor deficits (SMD). We designed a longitudinal protocol to assess the effects of cytoprotectants on SMD, microglial activation (MA) and SNL, and specifically tested whether the [...] Read more.
Although early reperfusion after stroke salvages the still-viable ischemic tissue, peri-infarct selective neuronal loss (SNL) can cause sensorimotor deficits (SMD). We designed a longitudinal protocol to assess the effects of cytoprotectants on SMD, microglial activation (MA) and SNL, and specifically tested whether the KCa3.1-blocker TRAM-34 would prevent SNL. Spontaneously hypertensive rats underwent 15 min middle-cerebral artery occlusion and were randomized into control or treatment group, which received TRAM-34 intraperitoneally for 4 weeks starting 12 h after reperfusion. SMD was assessed longitudinally using the sticky-label test. MA was quantified at day 14 using in vivo [11C]-PK111195 positron emission tomography (PET), and again across the same regions-of-interest template by immunofluorescence together with SNL at day 28. SMD recovered significantly faster in the treated group (p = 0.004). On PET, MA was present in 5/6 rats in each group, with no significant between-group difference. On immunofluorescence, both SNL and MA were present in 5/6 control rats and 4/6 TRAM-34 rats, with a non-significantly lower degree of MA but a significantly (p = 0.009) lower degree of SNL in the treated group. These findings document the utility of our longitudinal protocol and suggest that TRAM-34 reduces SNL and hastens behavioural recovery without marked MA blocking at the assessed time-points. Full article
(This article belongs to the collection Collection on Molecular and Cellular Neuroscience)
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Open AccessArticle
Is It Speech or Song? Effect of Melody Priming on Pitch Perception of Modified Mandarin Speech
Brain Sci. 2019, 9(10), 286; https://doi.org/10.3390/brainsci9100286 - 22 Oct 2019
Abstract
Tonal languages make use of pitch variation for distinguishing lexical semantics, and their melodic richness seems comparable to that of music. The present study investigated a novel priming effect of melody on the pitch processing of Mandarin speech. When a spoken Mandarin utterance [...] Read more.
Tonal languages make use of pitch variation for distinguishing lexical semantics, and their melodic richness seems comparable to that of music. The present study investigated a novel priming effect of melody on the pitch processing of Mandarin speech. When a spoken Mandarin utterance is preceded by a musical melody, which mimics the melody of the utterance, the listener is likely to perceive this utterance as song. We used functional magnetic resonance imaging to examine the neural substrates of this speech-to-song transformation. Pitch contours of spoken utterances were modified so that these utterances can be perceived as either speech or song. When modified speech (target) was preceded by a musical melody (prime) that mimics the speech melody, a task of judging the melodic similarity between the target and prime was associated with increased activity in the inferior frontal gyrus (IFG) and superior/middle temporal gyrus (STG/MTG) during target perception. We suggest that the pars triangularis of the right IFG may allocate attentional resources to the multi-modal processing of speech melody, and the STG/MTG may integrate the phonological and musical (melodic) information of this stimulus. These results are discussed in relation to subvocal rehearsal, a speech-to-song illusion, and song perception. Full article
(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)
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Open AccessPerspective
The Neuroprotective Effects of Melatonin: Possible Role in the Pathophysiology of Neuropsychiatric Disease
Brain Sci. 2019, 9(10), 285; https://doi.org/10.3390/brainsci9100285 - 21 Oct 2019
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Abstract
Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and [...] Read more.
Melatonin is a hormone that is secreted by the pineal gland. To date, melatonin is known to regulate the sleep cycle by controlling the circadian rhythm. However, recent advances in neuroscience and molecular biology have led to the discovery of new actions and effects of melatonin. In recent studies, melatonin was shown to have antioxidant activity and, possibly, to affect the development of Alzheimer’s disease (AD). In addition, melatonin has neuroprotective effects and affects neuroplasticity, thus indicating potential antidepressant properties. In the present review, the new functions of melatonin are summarized and a therapeutic target for the development of new drugs based on the mechanism of action of melatonin is proposed. Full article
(This article belongs to the Special Issue Neurogenesis and Gliogenesis in Health and Disease)
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Open AccessArticle
Overexpression of Macrophage Migration Inhibitory Factor and Its Homologue D-Dopachrome Tautomerase as Negative Prognostic Factor in Neuroblastoma
Brain Sci. 2019, 9(10), 284; https://doi.org/10.3390/brainsci9100284 - 19 Oct 2019
Viewed by 116
Abstract
Neuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that exerts [...] Read more.
Neuroblastoma (NB) represents one of the most frequent pediatric solid tumors. Macrophage migration inhibitory factor (MIF) is a cytokine exerting multiple biological functions. More recently, a second member of the MIF family of cytokine has been identified, the D-dopachrome tautomerase (DDT), that exerts several overlapping functions with MIF. Growing evidence suggests a key role for MIF and DDT in the development of cancer. The aim of this study is to characterize the prognostic value of MIF and DDT in NB. We show that higher expression levels of MIF and DDT in Stage 4 NB samples are associated with a poorer prognosis, independently of the presence of MYCN amplification. Moreover, higher levels of MIF are mostly enriched by Th1 cells, while lower levels of MIF are associated with an increased proportion of B cells, Cytotoxic T cells, Dendritic cells and Natural Killer T cells. We also show that treatment with the histone deacetylase (HDAC) inhibitor, vorinostat, of the NB cell line, SH-SY5Y, determines a significant reduction in the expression of both MIF and DDT. Finally, MIF and DDT inhibition by short interfering RNA is able to revert vincristine sensitivity in vitro. Overall, our data suggest that MIF exert pro-tumorigenic properties in NB, likely by dampening antigen presentation and cytotoxic immune responses, and we propose the HDAC inhibitors as a potential therapeutic strategy for NB patients. Full article
(This article belongs to the Section Developmental Neuroscience)
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Open AccessReview
A Review of Neurostimulation for Epilepsy in Pediatrics
Brain Sci. 2019, 9(10), 283; https://doi.org/10.3390/brainsci9100283 - 18 Oct 2019
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Abstract
Neurostimulation for epilepsy refers to the application of electricity to affect the central nervous system, with the goal of reducing seizure frequency and severity. We review the available evidence for the use of neurostimulation to treat pediatric epilepsy, including vagus nerve stimulation (VNS), [...] Read more.
Neurostimulation for epilepsy refers to the application of electricity to affect the central nervous system, with the goal of reducing seizure frequency and severity. We review the available evidence for the use of neurostimulation to treat pediatric epilepsy, including vagus nerve stimulation (VNS), responsive neurostimulation (RNS), deep brain stimulation (DBS), chronic subthreshold cortical stimulation (CSCS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). We consider possible mechanisms of action and safety concerns, and we propose a methodology for selecting between available options. In general, we find neurostimulation is safe and effective, although any high quality evidence applying neurostimulation to pediatrics is lacking. Further research is needed to understand neuromodulatory systems, and to identify biomarkers of response in order to establish optimal stimulation paradigms. Full article
(This article belongs to the Special Issue Epilepsy Surgery and Neuromodulation)
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Open AccessArticle
Is It Easy to Synchronize Our Minds When We Are Forced to Cooperate?
Brain Sci. 2019, 9(10), 282; https://doi.org/10.3390/brainsci9100282 - 18 Oct 2019
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Abstract
There is increasing scientific interest in elucidating the biological mechanisms underlying cooperative behaviors. Humans have developed a high degree of complexity in their cooperativity, which has been defined as hyper-cooperativity. An interesting biological marker to study how two individuals are emotionally linked when [...] Read more.
There is increasing scientific interest in elucidating the biological mechanisms underlying cooperative behaviors. Humans have developed a high degree of complexity in their cooperativity, which has been defined as hyper-cooperativity. An interesting biological marker to study how two individuals are emotionally linked when they cooperate is their psychophysiological synchronization (the overlapping of signals as indicators of Autonomous Nervous System activation). Hence, the main aim of this study was to explore participants’ psychophysiological synchronization, based on electrocardiograms (ECG) and galvanic skin response (GSR) signals in a sample of strangers who were set up to cooperate (n = 29 pairs of same sex strangers; mean age = 20.52 ± 1.72), compared to participants who were forced to compete (n = 22 pairs of same sex strangers; mean age = 20.45 ± 1.53) in a laboratory setting. Moreover, the roles of the participants’ gender and the outcomes (positive or negative) obtained in the cooperation were examined as potential moderators of this psychophysiological synchronization. Results showed a progressive increase in ECG and GSR signal synchronization in participants who cooperated, reaching the highest levels of synchronization during the recovery period. Moreover, cooperation induced higher GSR synchronization in comparison with competition. Finally, although gender played an important role in the psychophysiological synchronization during cooperation (women presented the highest overlapping of GSR signals), feedback about the participants’ performance was not significantly associated with their psychophysiological synchronization. Therefore, research in this field would help us to understand more about the body’s physiological responses to different types of social interactions, such as cooperation and competition, providing an opportunity to establish interaction strategies that would be physiologically desirable. Full article
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Open AccessCase Report
Post-Craniopharyngioma and Cranial Nerve-VI Palsy Update on a MS Patient with Major Depression and Concurrent Neuroimmune Conditions
Brain Sci. 2019, 9(10), 281; https://doi.org/10.3390/brainsci9100281 - 17 Oct 2019
Viewed by 199
Abstract
We report the case of a male multiple sclerosis (MS) patient with type 2 diabetes (T2D), asthma, major depression (MD or major depressive disorder, MDD), and other chronic conditions, after his recent difficulties with craniopharyngioma and cranial nerve-VI (CN6) palsy. In addition, we [...] Read more.
We report the case of a male multiple sclerosis (MS) patient with type 2 diabetes (T2D), asthma, major depression (MD or major depressive disorder, MDD), and other chronic conditions, after his recent difficulties with craniopharyngioma and cranial nerve-VI (CN6) palsy. In addition, we show magnetic resonance image and spectroscopy (MRI, MRS), Humphrey’s Visual Field (HVF), and retinal nerve fiber layer thickness (RNFLT) findings to explain the changes in the patient’s health, and discuss the methods that helped/help him sustain productivity and euthymia despite long-standing problems and new CNS changes. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis Research)
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Open AccessArticle
Association of Polygenic Liability for Alcohol Dependence and EEG Connectivity in Adolescence and Young Adulthood
Brain Sci. 2019, 9(10), 280; https://doi.org/10.3390/brainsci9100280 - 17 Oct 2019
Viewed by 154
Abstract
Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), [...] Read more.
Differences in the connectivity of large-scale functional brain networks among individuals with alcohol use disorders (AUD), as well as those at risk for AUD, point to dysfunctional neural communication and related cognitive impairments. In this study, we examined how polygenic risk scores (PRS), derived from a recent GWAS of DSM-IV Alcohol Dependence (AD) conducted by the Psychiatric Genomics Consortium, relate to longitudinal measures of interhemispheric and intrahemispheric EEG connectivity (alpha, theta, and beta frequencies) in adolescent and young adult offspring from the Collaborative Study on the Genetics of Alcoholism (COGA) assessed between ages 12 and 31. Our findings indicate that AD PRS (p-threshold < 0.001) was associated with increased fronto-central, tempo-parietal, centro-parietal, and parietal-occipital interhemispheric theta and alpha connectivity in males only from ages 18–31 (beta coefficients ranged from 0.02–0.06, p-values ranged from 10−6–10−12), but not in females. Individuals with higher AD PRS also demonstrated more performance deficits on neuropsychological tasks (Tower of London task, visual span test) as well as increased risk for lifetime DSM-5 alcohol and opioid use disorders. We conclude that measures of neural connectivity, together with neurocognitive performance and substance use behavior, can be used to further understanding of how genetic risk variants from large GWAS of AUD may influence brain function. In addition, these data indicate the importance of examining sex and developmental effects, which otherwise may be masked. Understanding of neural mechanisms linking genetic variants emerging from GWAS to risk for AUD throughout development may help to identify specific points when neurocognitive prevention and intervention efforts may be most effective. Full article
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Open AccessArticle
Pre- and Post-Treatment with Novel Antiepileptic Drug Oxcarbazepine Exerts Neuroprotective Effect in the Hippocampus in a Gerbil Model of Transient Global Cerebral Ischemia
Brain Sci. 2019, 9(10), 279; https://doi.org/10.3390/brainsci9100279 - 17 Oct 2019
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Abstract
Oxcarbazepine, an antiepileptic drug, has been reported to modulate voltage-dependent sodium channels, and it is commonly used in epilepsy treatment. In this study, we investigated the neuroprotective effect of oxcarbazepine in the hippocampus after transient ischemia in gerbils. Gerbils randomly received oxcarbazepine 100 [...] Read more.
Oxcarbazepine, an antiepileptic drug, has been reported to modulate voltage-dependent sodium channels, and it is commonly used in epilepsy treatment. In this study, we investigated the neuroprotective effect of oxcarbazepine in the hippocampus after transient ischemia in gerbils. Gerbils randomly received oxcarbazepine 100 or 200 mg/kg before and after transient ischemia. We examined its neuroprotective effect in the cornu ammonis 1 subfield of the gerbil hippocampus at 5 days after transient ischemia by using cresyl violet staining, neuronal nuclei immunohistochemistry and Fluoro-Jade B histofluorescence staining for neuroprotection, and by using glial fibrillary protein and ionized calcium-binding adapter molecule 1 immunohistochemistry for reaction of astrocytes and microglia, respectively. Pre- and post-treatment with 200 mg/kg of oxcarbazepine, but not 100 mg/kg of oxcarbazepine, protected pyramidal neurons of the cornu ammonis 1 subfield from transient ischemic damage. In addition, pre- and post-treatment with oxcarbazepine (200 mg/kg) significantly ameliorated astrocytes and microglia activation in the ischemic cornu ammonis 1 subfield. In brief, our current results indicate that post-treatment as well as pre-treatment with 200 mg/kg of oxcarbazepine can protect neurons from ischemic insults via attenuation of the glia reaction. Full article
(This article belongs to the collection Collection on Molecular and Cellular Neuroscience)
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Open AccessArticle
Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study
Brain Sci. 2019, 9(10), 278; https://doi.org/10.3390/brainsci9100278 - 17 Oct 2019
Viewed by 155
Abstract
Introduction: Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in [...] Read more.
Introduction: Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in cases of (1) late syphilis (acquired >2 years previously), (2) CD4+ cells ≤ 350/mm3 and/or a serum Venereal Disease Research Laboratory/Rapid Plasma Reagin (VDRL/RPR) title > 1:32, (3) “serological failure” after syphilis therapy, and (4) the use of alternative treatment for syphilis. In the present study, we aimed to verify the accuracy of the guideline’s criteria for the indication of LP in the suspicion of ANS in a cohort of PLWH. Methods: This retrospective study was carried out in a cohort of PLWH referred at a single medical center of a large academic hospital in Italy. Clinical and laboratory data of patients diagnosed with late syphilis were extracted from the cohort and analyzed. The European Guidelines of syphilis were adopted for patient management. Results: Out of a cohort of 713 PLWH, only 51 (7%) had a diagnosis of late syphilis and were therefore included in the study. Thirty-one subjects (61%) met one or more diagnostic criteria to perform LP: 39% (12/31) of patients undergoing LP had a diagnosis of ANS. The accuracy of predictive criteria for ANS, suggested by the guidelines, was 62% for RPR > 1:32 and 74% for CD4+ ≤ 350 cc/µL. The simultaneous occurrence of both criteria (RPR > 1:32 plus CD4+ ≤ 350 cc/µL) achieved a diagnostic accuracy of 59%. Interestingly, only 17% of patients who underwent LP for serological failure were eventually diagnosed positive for ANS. Conclusion: Asymptomatic neurosyphilis represents a challenging, but not uncommon, diagnosis. Therefore, it requires a careful investigation. Low CD4+ cell count and RPR > 1:32 remain excellent predictors of neurosyphilis, but have become the only acceptable predictors of ANS in PLWH. “Serologic failure” should be regarded with caution as a criterion to perform LP in order to investigate possible ANS in HIV-syphilis coinfected patients asymptomatic for neurological disorders. The retrospective nature of this single-site study may represent a limit to the interpretation of the data. Thus, larger clinical studies on the topic are warranted. Full article
(This article belongs to the Special Issue Update on HIV-Associated Neurocognitive Disorders (HAND))
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Open AccessArticle
An Investigation of Limbs Exercise as a Treatment in Improving the Psychomotor Speed in Older Adults with Mild Cognitive Impairment
Brain Sci. 2019, 9(10), 277; https://doi.org/10.3390/brainsci9100277 - 16 Oct 2019
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Abstract
Objectives: This study investigated the effects of therapeutic structured limb exercises intended to improve psychomotor speed in older adults with mild cognitive impairment (MCI). Methods: Forty-four patients with mild cognitive impairment who met the inclusion criteria were selected and assigned randomly to either [...] Read more.
Objectives: This study investigated the effects of therapeutic structured limb exercises intended to improve psychomotor speed in older adults with mild cognitive impairment (MCI). Methods: Forty-four patients with mild cognitive impairment who met the inclusion criteria were selected and assigned randomly to either an experimental group (22 patients) or a control group (22 patients). The numbers of participants were selected based on the calculated sample effect size (N = 38). The study involved a 10-week intervention, in which participants completed structured limb exercises during 60-min training sessions delivered three times per week. Forty-one subjects completed the experimental programme. Scores in the Finger Tapping Test (FTT), Purdue Pegboard Test (PPT) and Montreal Cognitive Assessment (MoCA), along with electroencephalography (EEG) data, were collected before, during and after the intervention. The experimental and control groups were compared using repeated measures analysis of variance. Results: The patients with MCI in the experimental group achieved significantly improved scores in the FTT, the PPT and all dimensions of the MoCA. Moreover, these patients exhibited significant increases in the alpha and beta EEG wave power values in all brain areas of MCI patients, indicating that limb exercise training positively influenced their brain functions. Conclusions: The results conclude that a structured therapeutic limb exercise intervention can effectively improve psychomotor speed in patients with MCI and mitigate declines in cognitive function. This training intervention appears to be effective as a treatment for community-dwelling patients with MCI. Full article
(This article belongs to the Special Issue Dementia and Cognitive Ageing)
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Open AccessArticle
The Role of the Embodiment Disturbance in the Anorexia Nervosa Psychopathology: A Network Analysis Study
Brain Sci. 2019, 9(10), 276; https://doi.org/10.3390/brainsci9100276 - 15 Oct 2019
Viewed by 275
Abstract
Anorexia Nervosa (AN) is characterized by body image distortion. From a phenomenological perspective, body image disturbance has been associated with a more profound disturbance encompassing disorders of the way persons experience their own body. The aim of this study was to disentangle the [...] Read more.
Anorexia Nervosa (AN) is characterized by body image distortion. From a phenomenological perspective, body image disturbance has been associated with a more profound disturbance encompassing disorders of the way persons experience their own body. The aim of this study was to disentangle the complex dynamics that connect the experience of one’s own body and self-identity to the psychopathological features of AN by applying a network analysis. Fifty-seven patients with AN restrictive subtype and 27 with AN binge–purging subtype participated in the study. Eating Disorders Inventory-2 and Identity and Eating Disorders subscores, measuring the embodiment dimensions, were included in the network. Two of the main dimensions of embodiment—feeling extraneous from one’s own body and feeling oneself through objective measures—were the nodes with the highest strength together with interoceptive awareness (IA). IA was a node included in several pathways connecting embodiment dimensions with most of the AN psychopathological dimensions. The centrality of the embodiment disorder suggests the importance of considering the body image disturbance in people with AN as resulting from their difficulty in experiencing inner states and as a tool to build its own self. This assumption may orient therapeutic interventions. Full article
(This article belongs to the Special Issue Psychotherapeutic Treatment for Anorexia Nervosa)
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Open AccessArticle
Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery
Brain Sci. 2019, 9(10), 275; https://doi.org/10.3390/brainsci9100275 - 15 Oct 2019
Viewed by 159
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR has been hampered due to its low bioavailability resulting from gastrointestinal degradation, inefficient permeability, and low aqueous solubility. The objective of the present research was to formulate and characterize naringenin-loaded chitosan nanoparticles (NAR NPs) for nose-to-brain delivery. The cellular uptake, cytotoxicity, and neuroprotective effects of NAR NPs were determined using the SH-SY5Y cell line in vitro. NAR NPs were prepared using the ionic gelation method and characterized by zetasizer, transmission electron microscopy (TEM), and field emission microscopy (FESEM). The average particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h in vitro release profile were 87.6 ± 8.47 nm, 0.31 ± 0.04, 15.36 ± 2.05 mV, 91.12 ± 2.99%, and 54.80 ± 4.22%, respectively. The percentage NAR permeation through nasal mucosa from NPs was found to be 67.90 ± 0.72%. Cellular uptake of prepared NPs was confirmed by fluorescence microscopy. Neuroprotective activity of NAR NPs was evaluated through viability assays and by estimating reactive oxygen species (ROS) levels. NAR NPs showed enhanced neuroprotective ability and antioxidant effect against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. However, animal studies are necessary to establish the potential of NAR NPs to be an effective carrier for the treatment of PD for nose-to-brain delivery. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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Open AccessBrief Report
Is a Virtual Reality Test Able to Predict Current and Retrospective ADHD Symptoms in Adulthood and Adolescence?
Brain Sci. 2019, 9(10), 274; https://doi.org/10.3390/brainsci9100274 - 13 Oct 2019
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Abstract
Despite the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood and adolescence, there are few objective, reliable instruments (based on patient performance) that have been shown to be able to predict current and retrospective ADHD symptoms. The present study aimed to explore [...] Read more.
Despite the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood and adolescence, there are few objective, reliable instruments (based on patient performance) that have been shown to be able to predict current and retrospective ADHD symptoms. The present study aimed to explore whether a validated VR test called Nesplora Aquarium is able to predict ADHD symptoms in adults and adolescents, based on both current and retrospective self-reports. A non-clinical sample of 156 adults and adolescents (70 women and 86 men) between 16 and 54 years of age (M = 21.23, SD = 8.04) took part in the study. Virtual reality (VR) variables such as the number of correct answers, omission and commission errors, among others, were used to predict current and retrospective self-reported symptoms of ADHD using multiple regression models. Correct answers and omission errors in the VR test significantly predicted both current and retrospective ADHD symptoms. However, only the number of perseveration errors and gender were able to significantly predict retrospective ADHD symptoms. These findings suggest that inattention problems tend to remain after adolescence, while perseveration errors (which have been related to impulsive behavior) and gender differences tend to diminish. Full article
(This article belongs to the Section Developmental Neuroscience)
Open AccessArticle
Oxidation Stress-Mediated MAPK Signaling Pathway Activation Induces Neuronal Loss in the CA1 and CA3 Regions of the Hippocampus of Mice Following Chronic Cold Exposure
Brain Sci. 2019, 9(10), 273; https://doi.org/10.3390/brainsci9100273 - 12 Oct 2019
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Abstract
Chronic stress can damage homeostasis and induce various primary diseases. Although chronic cold stress is becoming an increasing problem for people who must work or live in extreme environments, risk-induced diseases in the central nervous system remain unstudied. Male C57BL/6 mice were exposed [...] Read more.
Chronic stress can damage homeostasis and induce various primary diseases. Although chronic cold stress is becoming an increasing problem for people who must work or live in extreme environments, risk-induced diseases in the central nervous system remain unstudied. Male C57BL/6 mice were exposed to an environment of 4 °C, 3 h per day for 1, 2, and 3 weeks and homeostasis in the hippocampus and neuronal apoptosis were evaluated by Western blotting, immunohistochemistry, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and immunofluorescence. The phenomena of oxidation stress, MAPK signaling pathway activation, anti-oxidation protein release, neuronal apoptosis increases, and neuronal proliferation inhibition were demonstrated in the CA1 and CA3 regions of mouse hippocampal tissues following cold exposure. We speculated that these phenomena were mediated by the MAPK pathway and were closely linked with oxidative stress in the hippocampus. This study provides novel concepts regarding neurodegenerative diseases, suggesting that chronic cold stress may be a critical factor to induce neurodegenerative diseases. Full article
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Open AccessArticle
Safinamide in Clinical Practice: A Spanish Multicenter Cohort Study
Brain Sci. 2019, 9(10), 272; https://doi.org/10.3390/brainsci9100272 - 11 Oct 2019
Viewed by 181
Abstract
Background: Safinamide is an approved drug for the treatment of motor fluctuations of Parkinson’s Disease (PD) patients with a potential benefit on non-motor symptoms (NMS). Methods: A retrospective multicenter cohort study was conducted, in which the clinical effect of safinamide on both motor [...] Read more.
Background: Safinamide is an approved drug for the treatment of motor fluctuations of Parkinson’s Disease (PD) patients with a potential benefit on non-motor symptoms (NMS). Methods: A retrospective multicenter cohort study was conducted, in which the clinical effect of safinamide on both motor and NMS was assessed by the Clinical Global Impression of Change scale. Furthermore, we assessed the appearance of adverse events (AEs) and its effect on dyskinesia, that were also recorded in non-fluctuating PD patients and in those previously treated with rasagiline. Results: We included 213 PD patients who received safinamide in addition to their regular levodopa therapy. Thirty-five withdrew prematurely from safinamide, mainly because of AEs. Out of 178, clinical improvement on motor and NMS was found in 76.4% and 26.2%, respectively. A total of 44 reported AEs of mild intensity. We did not find a difference concerning the clinical benefit or AEs when comparing either patients who had or had not been taking Monoamine Oxidase B Inhibitor (MAOB-I) previously or between patients with and without motor complications. Conclusions: Safinamide is an effective and safe add-on to levodopa drug for PD patients. Moreover, safinamide could elicit an additional clinical improvement in PD patients previously treated with other MAOB-I and in non- fluctuating patients with suboptimal motor control. Full article
(This article belongs to the Special Issue Progression of Cognitive Decline in Older Adults with Parkinson’s)
Open AccessArticle
Mid-Frontal Theta Modulates Response Inhibition and Decision Making Processes in Emotional Contexts
Brain Sci. 2019, 9(10), 271; https://doi.org/10.3390/brainsci9100271 - 11 Oct 2019
Viewed by 164
Abstract
Inhibitory control is an integral part of executive functions. In this study, we report event-related spectral perturbation (ERSP) results from 15 healthy adults performing an emotional stop-signal task with the use of happy, disgusted, and neutral emotional faces. Our ERSP results at the [...] Read more.
Inhibitory control is an integral part of executive functions. In this study, we report event-related spectral perturbation (ERSP) results from 15 healthy adults performing an emotional stop-signal task with the use of happy, disgusted, and neutral emotional faces. Our ERSP results at the group level suggest that changes in low frequency oscillatory power for emotional and neutral conditions start at as early as 200 ms after stimulus onset and 300 ms before button press for successful go trials. To quantify the dynamics of trial-by-trial theta power, we applied the hierarchical drift diffusion model to single-trial ERSP at the mid-frontal electrode site for the go condition. Hierarchical drift diffusion modeling (HDDM) assigned higher frontal low-frequency oscillatory power for evidence accumulation in emotional contexts as compared to a neutral setting. Our results provide new evidence for dynamic modulation of sensory processing of go stimuli in inhibition and extend our knowledge for processing of response inhibition in emotional contexts. Full article
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Open AccessPerspective
Efficacy of Cell-Based Therapies for Traumatic Brain Injuries
Brain Sci. 2019, 9(10), 270; https://doi.org/10.3390/brainsci9100270 - 10 Oct 2019
Viewed by 273
Abstract
Traumatic brain injuries (TBIs) are a leading cause of death and disability. Additionally, growing evidence suggests a link between TBI-induced neuroinflammation and neurodegenerative disorders. Treatments for TBI patients are limited, largely focused on rehabilitation therapy, and ultimately, fail to provide long-term neuroprotective or [...] Read more.
Traumatic brain injuries (TBIs) are a leading cause of death and disability. Additionally, growing evidence suggests a link between TBI-induced neuroinflammation and neurodegenerative disorders. Treatments for TBI patients are limited, largely focused on rehabilitation therapy, and ultimately, fail to provide long-term neuroprotective or neurorestorative benefits. Because of the prevalence of TBI and lack of viable treatments, new therapies are needed which can promote neurological recovery. Cell-based treatments are a promising avenue because of their potential to provide multiple therapeutic benefits. Cell-based therapies can promote neuroprotection via modulation of inflammation and promote neurorestoration via induction of angiogenesis and neurogenesis. Neural stem/progenitor cell transplantations have been investigated in preclinical TBI models for their ability to directly contribute to neuroregeneration, form neural-like cells, and improve recovery. Mesenchymal stem cells (MSCs) have been investigated in clinical trials through multiple different routes of administration. Intravenous administration of MSCs appears most promising, demonstrating a robust safety profile, correlation with neurological improvements, and reductions in systemic inflammation following TBI. While still preliminary, evidence suggests cell-based therapies may become a viable treatment for TBI based on their ability to promote neuroregeneration and reduce inflammation. Full article
(This article belongs to the Special Issue Stem Cell Therapy in Neurodegenerative Diseases)
Open AccessArticle
High Serum Caspase-Cleaved Cytokeratin-18 Levels and Mortality of Traumatic Brain Injury Patients
Brain Sci. 2019, 9(10), 269; https://doi.org/10.3390/brainsci9100269 - 10 Oct 2019
Viewed by 148
Abstract
Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study [...] Read more.
Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study was to analyze whether serum CCCK-18 levels determined during the first week after TBI could predict early mortality (at 30 days). Methods: Severe TBI patients were included (considering severe when Glasgow Coma Scale < 9) in this observational and multicentre study. Serum CCCK-18 levels were determined at day 1 of TBI, and at days 4 and 8 after TBI. Results: Serum CCCK-18 levels at day 1 of TBI, and in the days 4 and 8 after TBI were higher (p < 0.001) in non-surviving than in surviving patients (34 and 90 patients, respectively) and could predict early mortality (p < 0.001 in the area under the curve). Conclusions: The new findings from our study were that serum CCCK-18 levels at any moment of the first week of TBI were higher in non-surviving patients and were able to predict early mortality. Full article
(This article belongs to the collection Collection on Clinical Neuroscience)
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Open AccessArticle
Ascending Axonal Degeneration of the Corticospinal Tract in Pure Hereditary Spastic Paraplegia: A Cross-Sectional DTI Study
Brain Sci. 2019, 9(10), 268; https://doi.org/10.3390/brainsci9100268 - 09 Oct 2019
Viewed by 217
Abstract
Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 [...] Read more.
Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI). Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 age and gender matched healthy controls. DTI was performed using a 3 T clinical scanner with whole brain tract-based spatial statistical (TBSS) analysis of the obtained fractional anisotropy (FA) data as well as a region-of-interest (ROI)-based analysis of affected tracts including the cervical spinal cord. We further conducted correlation analyses between DTI data and clinical characteristics. Results: TBSS analysis in HSP patients showed significantly decreased fractional anisotropy of the corpus callosum and the corticospinal tract compared to healthy controls. ROI-based analysis confirmed significantly lower FA in HSP compared to controls in the internal capsule (0.77 vs. 0.80, p = 0.048), the corpus callosum (0.84 vs. 0.87, p = 0.048) and the cervical spinal cord (0.72 vs. 0.79, p = 0.003). FA values of the cervical spinal cord significantly correlated with disease duration. Conclusion: DTI metrics of the corticospinal tract from the internal capsule to the cervical spine suggest microstructural damage and axonal degeneration of motor neurons. The CST at the level of the cervical spinal cord is thereby more severely affected than the intracranial part of the CST, suggesting an ascending axonal degeneration of the CST. Since there is a significant correlation with disease duration, FA may serve as a future progression marker for assessment of the disease course in HSP. Full article
(This article belongs to the collection Collection on Clinical Neuroscience)
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Open AccessArticle
Therapeutic Plasma Exchange in Multiple Sclerosis and Autoimmune Encephalitis: A Comparative Study of Indication, Efficacy, and Safety
Brain Sci. 2019, 9(10), 267; https://doi.org/10.3390/brainsci9100267 - 09 Oct 2019
Viewed by 279
Abstract
Therapeutic plasma exchange (TPE) is a well-established method of treatment for steroid-refractory relapses in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Little is known about indications and clinical responses to TPE in autoimmune encephalitis and other immune-mediated disorders of the central [...] Read more.
Therapeutic plasma exchange (TPE) is a well-established method of treatment for steroid-refractory relapses in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Little is known about indications and clinical responses to TPE in autoimmune encephalitis and other immune-mediated disorders of the central nervous system (CNS). We performed a retrospective chart review of patients with immune-mediated disorders of the CNS undergoing TPE at our tertiary care center between 2003 and 2015. The response to TPE within a 3- to 6-month follow-up was scored with an established rating system. We identified 40 patients including 21 patients with multiple sclerosis (MS, 52.5%), 12 with autoimmune encephalitis (AE, 30%), and 7 with other immune-mediated CNS disorders (17.5%). Among patients with AE, eight patients had definite AE (Immunolobulin G for N-methyl-D-aspartate receptor n = 4, Leucine-rich, glioma inactivated 1 n = 2, Ma 2 n = 1, and Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid n = 1). Intravenous immunoglobulins had been given prior to TPE in all but one patient with AE, and indications were dominated by acute psychosis and epileptic seizures. While TPE has a distinct place in the treatment sequence of different immune-mediated CNS disorders, we found consistent efficacy and safety. Further research should be directed toward alternative management strategies in non-responders. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis Research)
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Open AccessArticle
Tissue Plasminogen Activator and MRI Signs of Cerebral Small Vessel Disease
Brain Sci. 2019, 9(10), 266; https://doi.org/10.3390/brainsci9100266 - 05 Oct 2019
Viewed by 284
Abstract
Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify [...] Read more.
Cerebral small vessel disease (SVD) is one of the leading causes of cognitive impairment and stroke. The importance of endothelial dysfunction and high blood–brain barrier (BBB) permeability in pathogenesis, together with ischemia, is under discussion. The aim of this study was to clarify the relationship between tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), and magnetic resonance imaging (MRI) signs of SVD. We examined 71 patients (23 men and 48 women; mean age: 60.5 ± 6.9 years) with clinical and MRI signs of SVD, and 21 healthy volunteers with normal MRIs. All subjects underwent 3T MRI and measurements of t-PA and PAI-1 levels. An increase in t-PA level is correlated with the volume of white matter hyperintensities (WMH) (R = 0.289, p = 0.034), severity on the Fazekas scale (p = 0.000), and with the size of subcortical (p = 0.002) and semiovale (p = 0.008) perivascular spaces. The PAI-1 level is not correlated with the t-PA level or MRI signs of SVD. The correlation between t-PA and the degree of WMH and perivascular spaces’ enlargement, without a correlation with PAI-1 and lacunes, is consistent with the importance of t-PA in BBB disruption and its role in causing brain damage in SVD. Full article
(This article belongs to the collection Collection on Clinical Neuroscience)
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Open AccessReview
Autism Spectrum Disorder and miRNA: An Overview of Experimental Models
Brain Sci. 2019, 9(10), 265; https://doi.org/10.3390/brainsci9100265 - 03 Oct 2019
Viewed by 251
Abstract
Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder characterized by deficits in social interactions, communication, language, and in a limited repertoire of activities and interests. The etiology of ASD is very complex. Genetic, epigenetic, and environmental factors contribute to the onset of [...] Read more.
Autism spectrum disorder (ASD) is a complex neuropsychiatric disorder characterized by deficits in social interactions, communication, language, and in a limited repertoire of activities and interests. The etiology of ASD is very complex. Genetic, epigenetic, and environmental factors contribute to the onset of ASD. Researchers have shown that microRNAs (miRNAs) could be one of the possible causes associated with ASD. miRNAs are small noncoding mRNAs that regulate gene expression, and they are often linked to biological processes and implicated in neurodevelopment. This review aims to provide an overview of the animal models and the role of the different miRNAs involved in ASD. Therefore, the use of animal models that reproduce the ASD and the identification of miRNAs could be a useful predictive tool to study this disorder. Full article
Open AccessArticle
Weight Change after Striatal/Capsule Deep Brain Stimulation Relates to Connectivity to the Bed Nucleus of the Stria Terminalis and Hypothalamus
Brain Sci. 2019, 9(10), 264; https://doi.org/10.3390/brainsci9100264 - 03 Oct 2019
Viewed by 145
Abstract
Weight changes are insufficiently understood adverse events of deep brain stimulation. In this context, exploring neural networks of weight control may inform novel treatment strategies for weight-related disorders. In this study, we investigated weight changes after deep brain stimulation of the ventral striatum/ventral [...] Read more.
Weight changes are insufficiently understood adverse events of deep brain stimulation. In this context, exploring neural networks of weight control may inform novel treatment strategies for weight-related disorders. In this study, we investigated weight changes after deep brain stimulation of the ventral striatum/ventral capsule and to what extent changes are associated with connectivity to feeding-related networks. We retrospectively analyzed 25 patients undergoing deep brain stimulation for obsessive-compulsive disorder or substance dependency. Weight changes were assessed preoperatively and six to twelve months after surgery and then matched with individual stimulation sites and stimulation-dependent functional connectivity to a priori defined regions of interest that are involved in food intake. We observed a significant weight gain after six to twelve months of continuous stimulation. Weight increases were associated with medial/apical localization of stimulation sites and with connectivity to hypothalamic areas and the bed nucleus. Thus, deep brain stimulation of the ventral striatum/ventral capsule influences weight depending on localization and connectivity of stimulation sites. Bearing in mind the significance of weight-related disorders, we advocate further prospective studies investigating the neuroanatomical and neuropsychological underpinnings of food intake and their neuromodulatory therapeutic potential. Full article
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Open AccessArticle
The Serum Melatonin Levels and Mortality of Patients with Spontaneous Intracerebral Hemorrhage
Brain Sci. 2019, 9(10), 263; https://doi.org/10.3390/brainsci9100263 - 01 Oct 2019
Viewed by 257
Abstract
Objective: Providing melatonin in animal models with spontaneous intracerebral hemorrhage (SIH) has been associated with beneficial effects. However, to our knowledge, there are no published data on circulating melatonin levels regarding the prognosis of SIH patients. Therefore, the objectives of this study [...] Read more.
Objective: Providing melatonin in animal models with spontaneous intracerebral hemorrhage (SIH) has been associated with beneficial effects. However, to our knowledge, there are no published data on circulating melatonin levels regarding the prognosis of SIH patients. Therefore, the objectives of this study were to determine whether serum melatonin levels in SIH patients were associated with early mortality and whether they could be used as prognostic biomarkers. Methods: This observational and prospective study included patients with supratentorial and clinically severe SIH (defined as Glasgow Coma Scale GCS <9) admitted to the Intensive Care Units of six Spanish hospitals. Serum melatonin levels were determined at the time of severe SIH diagnosis. Mortality at 30 days was the study end-point. Results: Non-surviving patients (n = 46) showed higher serum melatonin levels (p < 0.001) than surviving (n = 54) patients. An area under the curve was found for the prediction of 30-day mortality by serum melatonin levels of 0.89 (95% CI = 0.81–0.94; p < 0.001). Multiple logistic regression analysis showed an association of serum melatonin levels with 30-day mortality (Odds Ratio = 8.16; 95% CI = 2.30–28.95; p = 0.001) after controlling for midline shift, glycemia, early evacuation of SIH, and Intracerebral hemorrhage (ICH) score. Conclusions: The novel findings by our study were the presence of higher serum melatonin levels in non-surviving patients than in surviving patients and the association of these levels with mortality. Full article
(This article belongs to the collection Collection on Clinical Neuroscience)
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Open AccessReview
Type 2 Diabetes Mellitus Increases the Risk of Late-Onset Alzheimer’s Disease: Ultrastructural Remodeling of the Neurovascular Unit and Diabetic Gliopathy
Brain Sci. 2019, 9(10), 262; https://doi.org/10.3390/brainsci9100262 - 29 Sep 2019
Viewed by 585
Abstract
Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is [...] Read more.
Type 2 diabetes mellitus (T2DM) and late-onset Alzheimer’s disease–dementia (LOAD) are increasing in global prevalence and current predictions indicate they will only increase over the coming decades. These increases may be a result of the concurrent increases of obesity and aging. T2DM is associated with cognitive impairments and metabolic factors, which increase the cellular vulnerability to develop an increased risk of age-related LOAD. This review addresses possible mechanisms due to obesity, aging, multiple intersections between T2DM and LOAD and mechanisms for the continuum of progression. Multiple ultrastructural images in female diabetic db/db models are utilized to demonstrate marked cellular remodeling changes of mural and glia cells and provide for the discussion of functional changes in T2DM. Throughout this review multiple endeavors to demonstrate how T2DM increases the vulnerability of the brain’s neurovascular unit (NVU), neuroglia and neurons are presented. Five major intersecting links are considered: i. Aging (chronic age-related diseases); ii. metabolic (hyperglycemia advanced glycation end products and its receptor (AGE/RAGE) interactions and hyperinsulinemia-insulin resistance (a linking linchpin); iii. oxidative stress (reactive oxygen–nitrogen species); iv. inflammation (peripheral macrophage and central brain microglia); v. vascular (macrovascular accelerated atherosclerosis—vascular stiffening and microvascular NVU/neuroglial remodeling) with resulting impaired cerebral blood flow. Full article
(This article belongs to the Section Neuroglia)
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Open AccessArticle
Short- and Mid-Term Improvement of Postural Balance after a Neurorehabilitation Program via Hippotherapy in Patients with Sensorimotor Impairment after Cerebral Palsy: A Preliminary Kinetic Approach
Brain Sci. 2019, 9(10), 261; https://doi.org/10.3390/brainsci9100261 - 29 Sep 2019
Viewed by 798
Abstract
There is still a lack of studies focused on trunk neurorehabilitation. Accordingly, it is unclear which therapeutic modalities are the most effective in improving static/dynamic balance after brain damage. We designed a pilot study on hippotherapy to assess its short- and mid-term effect [...] Read more.
There is still a lack of studies focused on trunk neurorehabilitation. Accordingly, it is unclear which therapeutic modalities are the most effective in improving static/dynamic balance after brain damage. We designed a pilot study on hippotherapy to assess its short- and mid-term effect on dynamic postural balance in patients with moderate-to-severe sensorimotor impairment secondary to cerebral palsy. Five patients aged 15.4 ± 6.1 years old were recruited. All of them had moderate-to-severe alterations of the muscle tone with associated postural balance impairment. Standing and walking were also impaired. Ten minutes horse riding simulator followed by twenty minutes hippotherapy session were conducted during five session days separated by one week each. We analyzed the displacement of the Center of Pressure (COP) on the sitting surface of the simulator’s saddle by means of a customized pressure pad. We measured the general behavior of the COP displacement as well as the postural adjustments when pace changed from walk to trot to walk during the sessions and among sessions. Statistical analysis revealed an improved postural control both by the end of the session and from session 1 to session 5. These results suggest that hippotherapy might support regularization of postural control in a long-term neurorehabilitation context. Full article
(This article belongs to the Section Clinical Neuroscience)
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Open AccessArticle
Comparative Volumetric Analysis of the Brain and Cerebrospinal Fluid in Chiari Type I Malformation Patients: A Morphological Study
Brain Sci. 2019, 9(10), 260; https://doi.org/10.3390/brainsci9100260 - 29 Sep 2019
Viewed by 285
Abstract
Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume [...] Read more.
Background: Chiari Type I malformation (CM-I) is defined as the migration of cerebellar tonsils from the foramen magnum in the caudal direction and is characterized by the disproportion of the neural structures. The aim of this study was to investigate the brain volume differences between CM-I patients and normal population using a comparative volumetric analysis. Methods: 140 patients with CM-I and 140 age- and sex-matched healthy controls were included in this study. The magnetic resonance imaging (MRI) data of both groups were analyzed with an automated MRI brain morphometry system. Total intracranial, cerebrum, cerebellum, brainstem, cerebrospinal fluid (CSF), and lateral ventricle volumes as well as cerebrum and cerebellum gray/white matter (GM/WM) volumes were measured. Statistical analysis was performed. Results: Both total CSF and lateral ventricle volumes and volume percentages (Pct) were found significantly higher in CM-I patients compared to the control group. However, there were significant decreases in cerebrum and cerebellum volume Pct in CM-I patients. Although there were no significant differences in cerebrum WM volumes and volume Pct, cerebrum GM volume Pct were found to be significantly lower in CM-I patients. Conclusions: Revealing the increased CSF and lateral ventricle volume, and volume Pct supported concomitant ventricular enlargement and hydrocephalus in some CM-I patients. Decreased cerebrum GM volume Pct compared to the control group might be the underlying factor of some cortical dysfunctions in CM-I patients. Full article
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