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Brain Sci., Volume 10, Issue 9 (September 2020) – 93 articles

Cover Story (view full-size image): Gulf War veterans suffer from a chronic multi-symptom disorder called Gulf War Illness (GWI) that has been associated with central nervous system (CNS) dysfunction. Symptoms of GWI overlap with other chronic conditions, including irritable bowel syndrome (IBS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To differentiate these disorders, we examined blood-based CNS autoantibody biomarkers among the illnesses. We found that veterans with GWI had much higher levels of autoantibodies to 9 out of 10 CNS proteins in their blood showing that GWI is a distinct disorder with more CNS involvement than ME/CFS or IBS. View this paper
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Open AccessReview
Can Brain Health Be Supported by Vitamin D-Based Supplements? A Critical Review
Brain Sci. 2020, 10(9), 660; https://doi.org/10.3390/brainsci10090660 - 22 Sep 2020
Cited by 2 | Viewed by 1002
Abstract
This review presents recent knowledge on the neuroprotective effects of vitamin D and their usefulness as oral supplementation when combined with other molecules, such as curcumin. A critical look at the effectiveness of vitamin D in this field is also provided. Vitamin D [...] Read more.
This review presents recent knowledge on the neuroprotective effects of vitamin D and their usefulness as oral supplementation when combined with other molecules, such as curcumin. A critical look at the effectiveness of vitamin D in this field is also provided. Vitamin D plays a crucial role in neuroprotection and in the cognitive decline associated with aging, where vitamin D’s levels are related to the levels of several neurotrophic factors. An important role of vitamin D has also been observed in the mechanism of neuroinflammation, which is the basis of several aging conditions, including cognitive decline and neurodegeration; furthermore, the neuroprotective effect of vitamin D in the cognitive decline of aging has recently been reported. For this reason, many food supplements created for humans contain vitamin D alone or combined with other molecules with antioxidant properties. However, recent studies also explored negative consequences of the use at a high dosage of vitamin D. Vitamin D in tissues or brain cells can also modulate calbindin-D28K, parvalbumin, and calretinin, and is involved in immune function, thanks also to the combination with curcumin. Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. In particular, curcumin is a potent immune-regulatory agent and its administration has been reported to attenuate cognitive impairments. These effects could be exploited in the future to control the mechanisms that lead to the brain decay typical of neurodegenerative diseases. Full article
(This article belongs to the Special Issue Biomakers of Brain Ageing)
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Open AccessArticle
Intentional Binding Effects in the Experience of Noticing the Regularity of a Perceptual-Motor Task
Brain Sci. 2020, 10(9), 659; https://doi.org/10.3390/brainsci10090659 - 22 Sep 2020
Viewed by 1305
Abstract
Noticing the regularity of the task is necessary to enhance motor performance. The experience of noticing further motivates improvement in motor performance. Motor control is explained by a comparator model that modifies the motor command to reduce discrepancies between sensory predictions and actual [...] Read more.
Noticing the regularity of the task is necessary to enhance motor performance. The experience of noticing further motivates improvement in motor performance. Motor control is explained by a comparator model that modifies the motor command to reduce discrepancies between sensory predictions and actual outcomes. A similar model could apply to sense of agency (SoA). SoA refers to the sensation of controlling one’s own actions and, through them, the outcomes in the external world. SoA may also be enhanced by the experience of noticing errors. We recently reported gradual enhancement of SoA in participants with high perceptual-motor performance. However, what component of the motor task changed the SoA is unclear. In this study, we aimed to investigate the influence over time of the experience of noticing during a motor task on SoA. Participants performed an implicit regularity perceptual-motor task and an intentional binding task (a method that can quantitatively measure SoA) simultaneously. We separated participants into groups after the experiment based on noticing or not noticing the regularity. SoA was gradually enhanced in the noticing group, compared with that of the non-noticing group. The results suggest that the experience of noticing may enhance SoA during perceptual-motor tasks. Full article
(This article belongs to the Special Issue The Role of Body in Brain Plasticity)
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Open AccessArticle
Effects of Paternal Preconception Vapor Alcohol Exposure Paradigms on Behavioral Responses in Offspring
Brain Sci. 2020, 10(9), 658; https://doi.org/10.3390/brainsci10090658 - 22 Sep 2020
Viewed by 673
Abstract
We and others previously reported that paternal preconception chronic ethanol exposure leads to molecular, physiological, and behavioral changes in offspring including reduced ethanol consumption and preference relative to controls. The goal of the present study was to further explore the impact of paternal [...] Read more.
We and others previously reported that paternal preconception chronic ethanol exposure leads to molecular, physiological, and behavioral changes in offspring including reduced ethanol consumption and preference relative to controls. The goal of the present study was to further explore the impact of paternal ethanol exposure on a wide variety of basal and drug-induced behavioral responses in first generation offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5–6 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. E-sired male offspring showed stress hyporesponsivity in a stress-induced hyperthermia assay and E-sired female offspring had reduced binge-like ethanol consumption in a drinking in the dark assay compared to C-sired offspring. E-sired offspring also showed altered sensitivity to a sedative/hypnotic dose of the GABAergic drug midazolam, but not ketamine or ethanol, in a loss of the righting response assay. E-sired offspring did not differ from controls in marble burying, novel object location, novel object recognition, social interaction, bottle-brush, novelty suppressed feeding, prepulse inhibition, every-other-day ethanol drinking, or home cage activity assays. This study adds to a growing body of literature suggesting that like in utero alcohol exposure, paternal preconception alcohol exposure can also have effects that persist and impact behavior of offspring. Full article
(This article belongs to the Special Issue The Genetics of Alcohol Use Disorder)
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Open AccessArticle
A Framework to Assess the Information Dynamics of Source EEG Activity and Its Application to Epileptic Brain Networks
Brain Sci. 2020, 10(9), 657; https://doi.org/10.3390/brainsci10090657 - 22 Sep 2020
Cited by 1 | Viewed by 834
Abstract
This study introduces a framework for the information-theoretic analysis of brain functional connectivity performed at the level of electroencephalogram (EEG) sources. The framework combines the use of common spatial patterns to select the EEG components which maximize the variance between two experimental conditions, [...] Read more.
This study introduces a framework for the information-theoretic analysis of brain functional connectivity performed at the level of electroencephalogram (EEG) sources. The framework combines the use of common spatial patterns to select the EEG components which maximize the variance between two experimental conditions, simultaneous implementation of vector autoregressive modeling (VAR) with independent component analysis to describe the joint source dynamics and their projection to the scalp, and computation of information dynamics measures (information storage, information transfer, statistically significant network links) from the source VAR parameters. The proposed framework was tested on simulated EEGs obtained mixing source signals generated under different coupling conditions, showing its ability to retrieve source information dynamics from the scalp signals. Then, it was applied to investigate scalp and source brain connectivity in a group of children manifesting episodes of focal and generalized epilepsy; the analysis was performed on EEG signals lasting 5 s, collected in two consecutive windows preceding and one window following each ictal episode. Our results show that generalized seizures are associated with a significant decrease from pre-ictal to post-ictal periods of the information stored in the signals and of the information transferred among them, reflecting reduced self-predictability and causal connectivity at the level of both scalp and source brain dynamics. On the contrary, in the case of focal seizures the scalp EEG activity was not discriminated across conditions by any information measure, while source analysis revealed a tendency of the measures of information transfer to increase just before seizures and to decrease just after seizures. These results suggest that focal epileptic seizures are associated with a reorganization of the topology of EEG brain networks which is only visible analyzing connectivity among the brain sources. Our findings emphasize the importance of EEG modeling approaches able to deal with the adverse effects of volume conduction on brain connectivity analysis, and their potential relevance to the development of strategies for prediction and clinical treatment of epilepsy. Full article
(This article belongs to the Special Issue Human Brain Dynamics: Latest Advances and Prospects)
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Open AccessArticle
Digital Devices Use and Language Skills in Children between 8 and 36 Month
Brain Sci. 2020, 10(9), 656; https://doi.org/10.3390/brainsci10090656 - 21 Sep 2020
Viewed by 1196
Abstract
Background: Over the past decade, the use of digital tools has grown and research evidence suggests that traditional media and new media offer both benefits and health risks for young children. The abilities to understand and use language represent two of the [...] Read more.
Background: Over the past decade, the use of digital tools has grown and research evidence suggests that traditional media and new media offer both benefits and health risks for young children. The abilities to understand and use language represent two of the most important competencies developed during the first 3 years of life through the interaction of the child with people, objects, events, and other environmental factors. The main goal of our study is to evaluate the relationship between digital devices use and language abilities in children between 8 and 36 month, also considering the influence of several factors. Materials and Methods: We conducted a cross-sectional observational study on digital devices use and language abilities in260 children (140 males = 54%) aged between 8 and 36 months (mean = 23.5 ± 7.18 months). All the parents completed a self-report questionnaire investigating the use of digital devices by their children, and a standardized questionnaire for the assessment of language skills (MacArthur-Bates). Linear regression analysis was used to evaluate the relation between different variables. Subsequent moderation analysis were performed to verify the influence of other factors. Results: We found a statistically significant negative relation between the total daily time of exposure to digital devices and the Actions and Gestures Quotient (ß = −0.397) in children between 8 and 17 months, and between the total daily time of exposure to digital devices and Lexical Quotient (ß = −0.224) in children between 18 and 36 months. Gender, level of education/job of parents, modality of use/content of digital device did not significantly affect the result of the regression analysis. Conclusion: In our study we found that a longer time of exposure to digital devices was related to lower mimic-gestural skills in children from 8–17 months and to lower language skills in children between 18 and 36 months, regardless of age, gender, socio-economic status, content, and modality of use. Further studies are needed to confirm and better understand this relation, but parents and pediatricians are advised to limit the use of digital devices by children and encourage the social interaction to support the learning of language and communication skills in this age group. Full article
(This article belongs to the Special Issue Neurological Diseases in Children)
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Open AccessArticle
Non-Immersive Virtual Reality for Post-Stroke Upper Extremity Rehabilitation: A Small Cohort Randomized Trial
Brain Sci. 2020, 10(9), 655; https://doi.org/10.3390/brainsci10090655 - 21 Sep 2020
Cited by 3 | Viewed by 1160
Abstract
Immersive and non-immersive virtual reality (NIVR) technology can supplement and improve standard physiotherapy and neurorehabilitation in post-stroke patients. We aimed to use MIRA software to investigate the efficiency of specific NIVR therapy as a standalone intervention, versus standardized physiotherapy for upper extremity rehabilitation [...] Read more.
Immersive and non-immersive virtual reality (NIVR) technology can supplement and improve standard physiotherapy and neurorehabilitation in post-stroke patients. We aimed to use MIRA software to investigate the efficiency of specific NIVR therapy as a standalone intervention, versus standardized physiotherapy for upper extremity rehabilitation in patients post-stroke. Fifty-five inpatients were randomized to control groups (applying standard physiotherapy and dexterity exercises) and experimental groups (applying NIVR and dexterity exercises). The two groups were subdivided into subacute (<six months post-stroke) and chronic (>six months to four years post-stroke survival patients). The following standardized tests were applied at baseline and after two weeks post-therapy: Fugl–Meyer Assessment for Upper Extremity (FMUE), the Modified Rankin Scale (MRS), Functional Independence Measure (FIM), Active Range of Motion (AROM), Manual Muscle Testing (MMT), Modified Ashworth Scale (MAS), and Functional Reach Test (FRT). The Kruskal–Wallis test was used to determine if there were significant differences between the groups, followed with pairwise comparisons. The Wilcoxon Signed-Rank test was used to determine the significance of pre to post-therapy changes. The Wilcoxon Signed-Rank test showed significant differences in all four groups regarding MMT, FMUE, and FIM assessments pre- and post-therapy, while for AROM, only experimental groups registered significant differences. Independent Kruskal–Wallis results showed that the subacute experimental group outcomes were statistically significant regarding the assessments, especially in comparison with the control groups. The results suggest that NIVR rehabilitation is efficient to be administered to post-stroke patients, and the study design can be used for a further trial, in the perspective that NIVR therapy can be more efficient than standard physiotherapy within the first six months post-stroke. Full article
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Open AccessArticle
Mitigating Effects of Liriope platyphylla on Nicotine-Induced Behavioral Sensitization and Quality Control of Compounds
Brain Sci. 2020, 10(9), 654; https://doi.org/10.3390/brainsci10090654 - 21 Sep 2020
Viewed by 649
Abstract
In this study we investigated the mitigating effects of Liriope platyphylla Wang et Tang extract on behavioral sensitization and the quantification of its major compounds. The extract of L. platyphylla reduces the expression of tyrosine hydroxylase (TH) protein, which is increased by nicotine, [...] Read more.
In this study we investigated the mitigating effects of Liriope platyphylla Wang et Tang extract on behavioral sensitization and the quantification of its major compounds. The extract of L. platyphylla reduces the expression of tyrosine hydroxylase (TH) protein, which is increased by nicotine, back to normal levels, and increases the expression of dopamine transporter (DAT) protein, which is reduced by nicotine, back to normal levels in PC12 cells. In this study, rats received nicotine (0.4 mg/kg, subcutaneously) only for seven days and then received extract of L. platyphylla (200 or 400 mg/kg, oral) 1 h prior to nicotine administration for an additional seven days. The extract of L. platyphylla reduced locomotor activity compared to the nicotine control group in rats. The extract of L. platyphylla significantly attenuated the repeated nicotine-induced DAT protein expression in the nucleus accumbens (NAc), but there was no effect on increased TH protein expression in the dorsal striatum. These findings suggest that L. platyphylla extract has a mitigating effect on nicotine-induced behavioral sensitization by modulating DAT protein expression in the NAc. For quality control of L. plathyphylla, spicatoside A and D, which are saponin compounds, were quantified in the L. platyphylla extract. The amounts of spicatoside A and D in L. platyphylla extract obtained from ultra-high-performance liquid chromatography with tandem mass spectrometry were 0.148 and 0.272 mg/g, respectively. The identification of these compounds in L. platyphylla, which can be used for quality control, provides important information for the development of drugs to treat nicotine dependence. Full article
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Open AccessReview
The Involvement of Hypothalamus–Pituitary–Adrenal (HPA) Axis in Suicide Risk
Brain Sci. 2020, 10(9), 653; https://doi.org/10.3390/brainsci10090653 - 21 Sep 2020
Cited by 5 | Viewed by 1026
Abstract
Stress and Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation play a major role in various pathophysiological processes associated with both mood disorders and suicidal behavior. We conducted a systematic review with the primary aim of clarifying the nature and extent of HPA axis activity and suicidal [...] Read more.
Stress and Hypothalamic–Pituitary–Adrenal (HPA) axis dysregulation play a major role in various pathophysiological processes associated with both mood disorders and suicidal behavior. We conducted a systematic review with the primary aim of clarifying the nature and extent of HPA axis activity and suicidal behavior. The second aim of this review was to investigate whether potential biomarkers related to HPA axis abnormalities act as individual susceptibility factors for suicide. The PRISMA statement for reporting systematic reviews was used. Only articles published in English peer-reviewed journals were considered for possible inclusion; we excluded case reports, meta-analyses, and systematic reviews, and studies that did not clearly report statistical analysis, diagnostic criteria, or the number of patients included. Overall, 36 articles on HPA axis and suicide risk met inclusion criteria and were reviewed. Studies that investigated tests detecting biomarkers and the role of early life stressors in suicide risk were also included. We found that HPA axis activity is involved in suicide risk, regardless of the presence or absence of psychiatric conditions. The HPA axis abnormalities, mainly characterized by hyperactivity of the HPA axis, may exert an important modulatory influence on suicide risk. Impaired stress response mechanisms contribute to suicide risk. Targeting HPA axis dysregulation might represent a fruitful strategy for identifying new treatment targets and improving suicide risk prediction. Full article
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Open AccessEditorial
Special Issue: Juvenile Onset Huntington’s Disease
Brain Sci. 2020, 10(9), 652; https://doi.org/10.3390/brainsci10090652 - 20 Sep 2020
Viewed by 684
(This article belongs to the Special Issue Juvenile Onset Huntington's Disease)
Open AccessArticle
Resveratrol Prevents GLUT3 Up-Regulation Induced by Middle Cerebral Artery Occlusion
Brain Sci. 2020, 10(9), 651; https://doi.org/10.3390/brainsci10090651 - 20 Sep 2020
Viewed by 840
Abstract
Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to [...] Read more.
Glucose transporter (GLUT)3 up-regulation is an adaptive response activated to prevent cellular damage when brain metabolic energy is reduced. Resveratrol is a natural polyphenol with anti-oxidant and anti-inflammatory features that protects neurons against damage induced in cerebral ischemia. Since transcription factors sensitive to oxidative stress and inflammation modulate GLUT3 expression, the purpose of this work was to assess the effect of resveratrol on GLUT3 expression levels after ischemia. Male Wistar rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by different times of reperfusion. Resveratrol (1.9 mg/kg; i. p.) was administered at the onset of the restoration of the blood flow. Quantitative-PCR and Western blot showed that MCAO provoked a substantial increase in GLUT3 expression in the ipsilateral side to the lesion of the cerebral cortex. Immunofluorescence assays indicated that GLUT3 levels were upregulated in astrocytes. Additionally, an important increase in GLUT3 occurred in other cellular types (e.g., damaged neurons, microglia, or infiltrated macrophages). Immunodetection of the microtubule-associated protein 2 (MAP2) showed that MCAO induced severe damage to the neuronal population. However, the administration of resveratrol at the time of reperfusion resulted in injury reduction. Resveratrol also prevented the MCAO-induced increase of GLUT3 expression. In conclusion, resveratrol protects neurons from damage induced by ischemia and prevents GLUT3 upregulation in the damaged brain that might depend on AMPK activation. Full article
(This article belongs to the Special Issue Biochemical Biomarkers and Neurodegenerative Diseases)
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Open AccessArticle
The Characteristics of Cognitive Impairment in ALS Patients Depend on the Lateralization of Motor Damage
Brain Sci. 2020, 10(9), 650; https://doi.org/10.3390/brainsci10090650 - 19 Sep 2020
Cited by 1 | Viewed by 776
Abstract
(1) Background: Cognitive features of patients with amyotrophic lateral sclerosis (ALS) have never been specifically analyzed according to the lateralization of motor impairment. In the present study we investigated the cognitive performances of ALS patients to describe the relationship between motor and cognitive [...] Read more.
(1) Background: Cognitive features of patients with amyotrophic lateral sclerosis (ALS) have never been specifically analyzed according to the lateralization of motor impairment. In the present study we investigated the cognitive performances of ALS patients to describe the relationship between motor and cognitive dysfunction, according to site and side of disease onset. (2) Methods: Six-hundred and nine ALS patients underwent a comprehensive neuropsychological evaluation at diagnosis in Turin ALS Centre Tests included—mini-mental state examination (MMSE), frontal assessment battery (FAB), trail-making test A/B (TMT A-B), digit span forward and backward (digit span FW/digit span BW), letter fluency test (FAS), category fluency test (CAT), Rey auditory verbal learning test (RAVLT), Babcock story recall test (BSRT), Rey-Osterrieth complex figure test (ROCFT), Wisconsin card sorting test (WCST), Raven’s coloured progressive matrices (CPM47). Cognitive performances of patients, grouped by side and site of onset, were statistically compared using z-scores, as appropriate. (3) Results: Bulbar patients and bilateral spinal onset patients (Sbil) were generally characterized by lower cognitive performances in most neuropsychological tests, when compared to patients with lateralized onset (right-side spinal onset, Sri and left-side spinal onset, Sle). Digit span backward and visual memory task (ROCFT) median z-scores were significantly higher, reflecting a better cognitive performance, in Sri patients when compared to bulbar/Sbil patients, while verbal memory tasks (RAVLT and BRST) resulted in significantly higher scores in Sle patients. Our results are in keeping with hemispheric functional lateralization of language and visuospatial abilities. (4) Conclusions: In ALS patients, as in other neurodegenerative diseases, we found a direct relationship between lateralized motor and cognitive features. Full article
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Open AccessArticle
Tele-Assisted Behavioral Intervention for Families with Children with Autism Spectrum Disorders: A Randomized Control Trial
Brain Sci. 2020, 10(9), 649; https://doi.org/10.3390/brainsci10090649 - 18 Sep 2020
Cited by 3 | Viewed by 1355
Abstract
Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited. Methods: This randomized control trial—ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID [...] Read more.
Background: Telehealth is useful for both autism spectrum disorder (ASD) diagnosis and treatment, but studies with a direct comparison between teletherapy and traditional in-person therapy are limited. Methods: This randomized control trial—ISRCTN (International Standard Randomised Controlled Trial Number) primary clinical trial registry ID ISRCTN15312724—was aimed at comparing the effect of a tele-assisted and in-person intervention based on a behavioral intervention protocol for families with children affected by ASDs. Forty-two parents with children with autism (30 months to 10 years old) were randomly assigned to 12 sessions of an applied behavioral analysis (ABA) intervention implemented in an individual and group setting, either with or without the inclusion of tele-assistance. Pre- and postintervention assessments were conducted using the Home Situation Questionnaire (HSQ-ASD) and the Parental Stress Index (PSI/SF). Results: Substantial improvements in the perception and management of children’s behavior by parents, as well as in the influence of a reduction in parent stress levels on said children’s behavior through the use of a tele-assisted intervention, were obtained. Conclusions: This randomized controlled trial demonstrates the evidence-based potential for telehealth to improve treatment of ASDs. Full article
(This article belongs to the Special Issue Advances in Autism Research)
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Open AccessOpinion
Promotion of Poststroke Motor-Function Recovery with Repetitive Transcranial Magnetic Stimulation by Regulating the Interhemispheric Imbalance
Brain Sci. 2020, 10(9), 648; https://doi.org/10.3390/brainsci10090648 - 18 Sep 2020
Cited by 1 | Viewed by 794
Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain-stimulation technique that transiently modulates cerebral cortex excitability, achieving overall positive results in poststroke motor-function recovery. Excessive inhibition of the ipsilesional-affected hemisphere by the contralesional-unaffected hemisphere has seriously hindered poststroke motor-function recovery. Hence, intracortical disinhibition [...] Read more.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain-stimulation technique that transiently modulates cerebral cortex excitability, achieving overall positive results in poststroke motor-function recovery. Excessive inhibition of the ipsilesional-affected hemisphere by the contralesional-unaffected hemisphere has seriously hindered poststroke motor-function recovery. Hence, intracortical disinhibition can be used as an approach to managing poststroke brain injury. This technique promotes neural plasticity for faster motor-function recovery. rTMS relieves unilateral inhibition of the brain function by regulatinga interhemispheric-imbalanced inhibition. This paper summarized 12 studies from 2016 to date, focusing on rTMS on motor function after acute and chronic stroke by regulating the interhemispheric imbalance of inhibitory inputs. Although rTMS studies have shown promising outcomes on recovery of motor functions in stroke patients, different intervention methods may lead to discrepancies in results. A uniform optimal stimulus model cannot routinely be used, mainly due to the stimulus schemes, stroke types and outcome-measuring differences among studies. Thus, the effect of rTMS on poststroke motor-function recovery should be investigated further to standardize the rTMS program for optimal poststroke motor-function recovery. More randomized, placebo-controlled clinical trials with standardized rTMS protocols are needed to ensure the effectiveness of the treatment. Full article
(This article belongs to the Special Issue Neuromodulation and Executive Control of Human Movements)
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Open AccessArticle
Gender Differences and Unfairness Processing during Economic and Moral Decision-Making: A fNIRS Study
Brain Sci. 2020, 10(9), 647; https://doi.org/10.3390/brainsci10090647 - 17 Sep 2020
Cited by 1 | Viewed by 1098
Abstract
Decisional conflicts have been investigated with social decision-making tasks, which represent good models to elicit social and emotional dynamics, including fairness perception. To explore these issues, we created two modified versions of the UG framed within an economic vs. a moral context that [...] Read more.
Decisional conflicts have been investigated with social decision-making tasks, which represent good models to elicit social and emotional dynamics, including fairness perception. To explore these issues, we created two modified versions of the UG framed within an economic vs. a moral context that included two kinds of unfair offers: advantageous (upside, U) or disadvantageous (downside, D) from the responder’s perspective, and vice-versa for the proponent. The hemodynamic activity of 36 participants, 20 females and 16 males, was continuously recorded with fNIRS to investigate the presence of general or specific circuits between the different experimental conditions. Results showed that disadvantageous offers (D) are associated with an increased widespread cortical activation. Furthermore, we found that advantageous moral choices at the expense of others (U) were related to the activation of the right prefrontal cortex. Finally, we found gender-related differences in brain activations in the different frameworks. In particular, the DLPFC was recruited by females during the economic task, and by males during the moral frame. In conclusion, the present study confirmed and expanded previous data about the role of the prefrontal cortices in decision-making, suggesting the need for further studies to understand better the different prefrontal networks serving moral and economic decisions also considering gender-related differences. Full article
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Open AccessArticle
Loss of the Mitochondrial Fission GTPase Drp1 Contributes to Neurodegeneration in a Drosophila Model of Hereditary Spastic Paraplegia
Brain Sci. 2020, 10(9), 646; https://doi.org/10.3390/brainsci10090646 - 17 Sep 2020
Viewed by 1137
Abstract
Mitochondrial morphology, distribution and function are maintained by the opposing forces of mitochondrial fission and fusion, the perturbation of which gives rise to several neurodegenerative disorders. The large guanosine triphosphate (GTP)ase dynamin-related protein 1 (Drp1) is a critical regulator of mitochondrial fission by [...] Read more.
Mitochondrial morphology, distribution and function are maintained by the opposing forces of mitochondrial fission and fusion, the perturbation of which gives rise to several neurodegenerative disorders. The large guanosine triphosphate (GTP)ase dynamin-related protein 1 (Drp1) is a critical regulator of mitochondrial fission by mediating membrane scission, often at points of mitochondrial constriction at endoplasmic reticulum (ER)-mitochondrial contacts. Hereditary spastic paraplegia (HSP) subtype SPG61 is a rare neurodegenerative disorder caused by mutations in the ER-shaping protein Arl6IP1. We have previously reported defects in both the ER and mitochondrial networks in a Drosophila model of SPG61. In this study, we report that knockdown of Arl6IP1 lowers Drp1 protein levels, resulting in reduced ER–mitochondrial contacts and impaired mitochondrial load at the distal ends of long motor neurons. Increasing mitochondrial fission, by overexpression of wild-type Drp1 but not a dominant negative Drp1, increases ER–mitochondrial contacts, restores mitochondrial load within axons and partially rescues locomotor deficits. Arl6IP1 knockdown Drosophila also demonstrate impaired autophagic flux and an accumulation of ubiquitinated proteins, which occur independent of Drp1-mediated mitochondrial fission defects. Together, these findings provide evidence that impaired mitochondrial fission contributes to neurodegeneration in this in vivo model of HSP. Full article
(This article belongs to the Special Issue Mitochondria as Therapeutic Target for Acute Brain Pathologies)
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Open AccessFeature PaperArticle
How to Construct a Bottom-Up Nomothetic Network Model and Disclose Novel Nosological Classes by Integrating Risk Resilience and Adverse Outcome Pathways with the Phenome of Schizophrenia
Brain Sci. 2020, 10(9), 645; https://doi.org/10.3390/brainsci10090645 - 17 Sep 2020
Cited by 4 | Viewed by 785
Abstract
Current case definitions of schizophrenia (DSM-5, ICD), made through a consensus among experts, are not cross-validated and lack construct reliability validity. The aim of this paper is to explain how to use bottom-up pattern recognition approaches to construct a reliable and replicable nomothetic [...] Read more.
Current case definitions of schizophrenia (DSM-5, ICD), made through a consensus among experts, are not cross-validated and lack construct reliability validity. The aim of this paper is to explain how to use bottom-up pattern recognition approaches to construct a reliable and replicable nomothetic network reflecting the direct effects of risk resilience (RR) factors, and direct and mediated effects of both RR and adverse outcome pathways (AOPs) on the schizophrenia phenome. This study was conducted using data from 40 healthy controls and 80 patients with schizophrenia. Using partial least squares (PLS) analysis, we found that 39.7% of the variance in the phenomenome (lowered self-reported quality of life) was explained by the unified effects of AOPs (IgA to tryptophan catabolites, LPS, and the paracellular pathway, cytokines, and oxidative stress biomarkers), the cognitome (memory and executive deficits), and symptomatome (negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, formal thought disorders); 55.8% of the variance in the symptomatome was explained by a single trait extracted from AOPs and the cognitome; and 22.0% of the variance in the latter was explained by the RR (Q192R polymorphism and CMPAase activity, natural IgM, and IgM levels to zonulin). There were significant total effects (direct + mediated) of RR and AOPs on the symptomatome and the phenomenome. In the current study, we built a reliable nomothetic network that reflects the associations between RR, AOPs, and the phenome of schizophrenia and discovered new diagnostic subclasses of schizophrenia based on unified RR, AOPs, and phenome scores. Full article
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Open AccessArticle
Functional Connectivity Analysis on Resting-State Electroencephalography Signals Following Chiropractic Spinal Manipulation in Stroke Patients
Brain Sci. 2020, 10(9), 644; https://doi.org/10.3390/brainsci10090644 - 17 Sep 2020
Viewed by 1545
Abstract
Stroke impairments often present as cognitive and motor deficits, leading to a decline in quality of life. Recovery strategy and mechanisms, such as neuroplasticity, are important factors, as these can help improve the effectiveness of rehabilitation. The present study investigated chiropractic spinal manipulation [...] Read more.
Stroke impairments often present as cognitive and motor deficits, leading to a decline in quality of life. Recovery strategy and mechanisms, such as neuroplasticity, are important factors, as these can help improve the effectiveness of rehabilitation. The present study investigated chiropractic spinal manipulation (SM) and its effects on resting-state functional connectivity in 24 subacute to chronic stroke patients monitored by electroencephalography (EEG). Functional connectivity of both linear and non-linear coupling was estimated by coherence and phase lag index (PLI), respectively. Non-parametric cluster-based permutation tests were used to assess the statistical significance of the changes in functional connectivity following SM. Results showed a significant increase in functional connectivity from the PLI metric in the alpha band within the default mode network (DMN). The functional connectivity between the posterior cingulate cortex and parahippocampal regions increased following SM, t (23) = 10.45, p = 0.005. No significant changes occurred following the sham control procedure. These findings suggest that SM may alter functional connectivity in the brain of stroke patients and highlights the potential of EEG for monitoring neuroplastic changes following SM. Furthermore, the altered connectivity was observed between areas which may be affected by factors such as decreased pain perception, episodic memory, navigation, and space representation in the brain. However, these factors were not directly monitored in this study. Therefore, further research is needed to elucidate the underlying mechanisms and clinical significance of the observed changes. Full article
(This article belongs to the Special Issue Brain Plasticity and Motor Control—Series II)
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Open AccessArticle
Inter-Session Reliability of Functional Near-Infrared Spectroscopy at the Prefrontal Cortex While Walking in Multiple Sclerosis
Brain Sci. 2020, 10(9), 643; https://doi.org/10.3390/brainsci10090643 - 17 Sep 2020
Cited by 2 | Viewed by 983
Abstract
Many established technologies are limited in analyzing the executive functions in motion, especially while walking. Functional near-infrared spectroscopy (fNIRS) fills this gap. The aim of the study is to investigate the inter-session reliability (ISR) of fNIRS-derived parameters at the prefrontal cortex while walking [...] Read more.
Many established technologies are limited in analyzing the executive functions in motion, especially while walking. Functional near-infrared spectroscopy (fNIRS) fills this gap. The aim of the study is to investigate the inter-session reliability (ISR) of fNIRS-derived parameters at the prefrontal cortex while walking in people with multiple sclerosis (MS) and healthy control (HC) individuals. Twenty people with MS/HC individuals walked a 12 m track back and forth over 6 min. The primary outcomes were the absolute and relative reliability of the mean, slope coefficient (SC), and area under the curve (A) of the oxy-/deoxyhemoglobin concentrations (HbO/HbR) in the Brodmann areas (BA) 9/46/10. The SC and the A of HbO exhibited a fair ISR in BA10 in people with MS. For the mean and A of the HbR, almost all areas observed revealed a fair ISR. Overall, the ISR was better for HbR than HbO. A fair to excellent ISR was found for most BA of the prefrontal cortex in HC individuals. In total, the ISR of the analyzed fNIRS-derived parameters was limited. To improve the ISR, confounders such as fatigue and mind wandering should be minimized. When reporting the ISR, the focus should be on the mean/A rather than SC. Full article
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Open AccessCase Report
Evaluation of Automatic Segmentation of Thalamic Nuclei through Clinical Effects Using Directional Deep Brain Stimulation Leads: A Technical Note
Brain Sci. 2020, 10(9), 642; https://doi.org/10.3390/brainsci10090642 - 17 Sep 2020
Viewed by 714
Abstract
Automatic anatomical segmentation of patients’ anatomical structures and modeling of the volume of tissue activated (VTA) can potentially facilitate trajectory planning and post-operative programming in deep brain stimulation (DBS). We demonstrate an approach to evaluate the accuracy of such software for the ventral [...] Read more.
Automatic anatomical segmentation of patients’ anatomical structures and modeling of the volume of tissue activated (VTA) can potentially facilitate trajectory planning and post-operative programming in deep brain stimulation (DBS). We demonstrate an approach to evaluate the accuracy of such software for the ventral intermediate nucleus (VIM) using directional leads. In an essential tremor patient with asymmetrical brain anatomy, lead placement was adjusted according to the suggested segmentation made by the software (Brainlab). Postoperatively, we used directionality to assess lead placement using side effect testing (internal capsule and sensory thalamus). Clinical effects were then compared to the patient-specific visualization and VTA simulation in the GUIDE™ XT software (Boston Scientific). The patient’s asymmetrical anatomy was correctly recognized by the software and matched the clinical results. VTA models matched best for dysarthria (6 out of 6 cases) and sensory hand side effects (5/6), but least for facial side effects (1/6). Best concordance was observed for the modeled current anterior and back spread of the VTA, worst for the current side spread. Automatic anatomical segmentation and VTA models can be valuable tools for DBS planning and programming. Directional DBS leads allow detailed postoperative assessment of the concordance of such image-based simulation and visualization with clinical effects. Full article
(This article belongs to the Special Issue Deep Brain Stimulation in Essential Tremor)
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Open AccessBrief Report
Dynamic Cerebral Autoregulation Post Endovascular Thrombectomy in Acute Ischemic Stroke
Brain Sci. 2020, 10(9), 641; https://doi.org/10.3390/brainsci10090641 - 16 Sep 2020
Cited by 1 | Viewed by 869
Abstract
The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context [...] Read more.
The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context of EVT may assist with post-procedure hemodynamic optimization to prevent complications. We examined cerebral autoregulation in 107 patients with an LVO in the anterior circulation (proximal middle cerebral artery (M1/2) and internal cerebral artery (ICA) terminus) who had been treated using an EVT. Dynamic cerebral autoregulation was assessed at multiple time points, ranging from less than 24 hours to 5 days following last seen well (LSW) time, using transcranial Doppler ultrasound recordings and transfer function analysis. Complete (Thrombolysis in Cerebral Infarction (TICI) 3) recanalization was associated with a more favorable autoregulation profile compared with TICI 2b or poorer recanalization (p < 0.05), which is an effect that was present after accounting for differences in the infarct volumes. Less effective autoregulation in the first 24 h following the LSW time was associated with increased rates of parenchymal hematoma types 1 and 2 hemorrhagic transformations (PH1–PH2). These data suggest that patients with incomplete recanalization and poor autoregulation (especially within the first 24 h post-LSW time) may warrant closer blood pressure monitoring and control in the first few days post ictus. Full article
(This article belongs to the Special Issue Cerebral Autoregulation and Cardiovascular Health)
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Open AccessArticle
Global Neural Activities Changes under Human Inhibitory Control Using Translational Scenario
Brain Sci. 2020, 10(9), 640; https://doi.org/10.3390/brainsci10090640 - 16 Sep 2020
Viewed by 724
Abstract
This study presents a new approach to exploring human inhibition in a realistic scenario. In previous inhibition studies, the stimulus design of go/no-go task generally used a simple symbol for the go and stop signals. We can understand the neural activity of inhibition [...] Read more.
This study presents a new approach to exploring human inhibition in a realistic scenario. In previous inhibition studies, the stimulus design of go/no-go task generally used a simple symbol for the go and stop signals. We can understand the neural activity of inhibition through simple symbol scenario. In the real world, situations of human inhibition are more complex than performing an experiment in the laboratory scale. How to explore the neural activities of inhibition in a realistic environment is more complex. Consequently, we designed a battlefield scenario to investigate the neural activities of inhibition in a more realistic environmental setting. The battlefield scenario provides stronger emotion, motivation and real-world experiences for participants during inhibition. In the battlefield scenario, the signs of fixation, go and stop were replaced by images of a sniper scope, a target and a non-target. The battlefield scenario is a shooting game between the enemy and the soldiers. In battlefield scenario participants played the role of the soldiers for shooting target and to stop shooting when a non-target appeared. Electroencephalography (EEG) signals from twenty participants were acquired and analyzed using independent component analysis (ICA) and dipole source localization method. The results of event-related potential (ERP) showed a significant modulation of the peaks N1, N2 and P3 in the frontal and cingulate cortices under inhibitory control. The partially overlapping ERP N2 and P3 waves were associated with inhibition in the frontal cortex. The ERP N2, N1 and P3 waves in the cingulate cortex are related to sustained attention, motivation, emotion and inhibitory control. In addition, the event-related spectral perturbation (ERSP) results shows that the powers of the delta and theta bands increased significantly in the frontal and cingulate cortices under human inhibitory control. The EEG-ERP waves and power spectra in the frontal and cingulate cortices were found more increased than in the parietal, occipital, left and right motor cortices after successful stop. These findings provide new insights to understand the global neural activities changes during human inhibitory control with realistic environmental scenario. Full article
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Open AccessReview
Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms
Brain Sci. 2020, 10(9), 639; https://doi.org/10.3390/brainsci10090639 - 16 Sep 2020
Cited by 5 | Viewed by 1038
Abstract
When a low-salience stimulus of any type of sensory modality—auditory, visual, tactile—immediately precedes an unexpected startle-like stimulus, such as the acoustic startle reflex, the startle motor reaction becomes less pronounced or is even abolished. This phenomenon is known as prepulse inhibition (PPI), and [...] Read more.
When a low-salience stimulus of any type of sensory modality—auditory, visual, tactile—immediately precedes an unexpected startle-like stimulus, such as the acoustic startle reflex, the startle motor reaction becomes less pronounced or is even abolished. This phenomenon is known as prepulse inhibition (PPI), and it provides a quantitative measure of central processing by filtering out irrelevant stimuli. As PPI implies plasticity of a reflex and is related to automatic or attentional processes, depending on the interstimulus intervals, this behavioral paradigm might be considered a potential marker of short- and long-term plasticity. Assessment of PPI is directly related to the examination of neural sensorimotor gating mechanisms, which are plastic-adaptive operations for preventing overstimulation and helping the brain to focus on a specific stimulus among other distracters. Despite their obvious importance in normal brain activity, little is known about the intimate physiology, circuitry, and neurochemistry of sensorimotor gating mechanisms. In this work, we extensively review the current literature focusing on studies that used state-of-the-art techniques to interrogate the neuroanatomy, connectomics, neurotransmitter-receptor functions, and sex-derived differences in the PPI process, and how we can harness it as biological marker in neurological and psychiatric pathology. Full article
(This article belongs to the Special Issue Central Auditory Plasticity)
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Open AccessArticle
Differentiating High-Grade Gliomas from Brain Metastases at Magnetic Resonance: The Role of Texture Analysis of the Peritumoral Zone
Brain Sci. 2020, 10(9), 638; https://doi.org/10.3390/brainsci10090638 - 16 Sep 2020
Viewed by 753
Abstract
High-grade gliomas (HGGs) and solitary brain metastases (BMs) have similar imaging appearances, which often leads to misclassification. In HGGs, the surrounding tissues show malignant invasion, while BMs tend to displace the adjacent area. The surrounding edema produced by the two cannot be differentiated [...] Read more.
High-grade gliomas (HGGs) and solitary brain metastases (BMs) have similar imaging appearances, which often leads to misclassification. In HGGs, the surrounding tissues show malignant invasion, while BMs tend to displace the adjacent area. The surrounding edema produced by the two cannot be differentiated by conventional magnetic resonance (MRI) examinations. Forty-two patients with pathology-proven brain tumors who underwent conventional pretreatment MRIs were retrospectively included (HGGs, n = 16; BMs, n = 26). Texture analysis of the peritumoral zone was performed on the T2-weighted sequence using dedicated software. The most discriminative texture features were selected using the Fisher and the probability of classification error and average correlation coefficients. The ability of texture parameters to distinguish between HGGs and BMs was evaluated through univariate, receiver operating, and multivariate analyses. The first percentile and wavelet energy texture parameters were independent predictors of HGGs (75–87.5% sensitivity, 53.85–88.46% specificity). The prediction model consisting of all parameters that showed statistically significant results at the univariate analysis was able to identify HGGs with 100% sensitivity and 66.7% specificity. Texture analysis can provide a quantitative description of the peritumoral zone encountered in solitary brain tumors, that can provide adequate differentiation between HGGs and BMs. Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
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Open AccessOpinion
Hyperhomocysteinemia and Endothelial Dysfunction in Multiple Sclerosis
Brain Sci. 2020, 10(9), 637; https://doi.org/10.3390/brainsci10090637 - 16 Sep 2020
Cited by 1 | Viewed by 768
Abstract
Endothelial dysfunction is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and the prothrombogenic state. The most [...] Read more.
Endothelial dysfunction is recognized as one of the leading factors in the pathogenesis of diseases of the central nervous system of various etiologies. Numerous studies have shown the role of hyperhomocysteinemia in the development of endothelial dysfunction and the prothrombogenic state. The most important condition in the development of multiple sclerosis (MS) is a dysregulation of the blood-brain barrier (BBB) and transendothelial leukocyte migration. It has been proven that homocysteine also contributes to the damage of neurons by the mechanism of excitotoxicity and the induction of the apoptosis of neurons. These processes can be one of the factors of neurodegenerative brain damage, which plays a leading role in the progression of MS. This review describes the pleiotropic effect of homocysteine on these processes and its role in MS pathogenesis. Full article
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Open AccessArticle
Can Pallidal Deep Brain Stimulation Rescue Borderline Dystonia? Possible Coexistence of Functional (Psychogenic) and Organic Components
Brain Sci. 2020, 10(9), 636; https://doi.org/10.3390/brainsci10090636 - 15 Sep 2020
Viewed by 934
Abstract
The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are [...] Read more.
The diagnosis and treatment of functional movement disorders are challenging for clinicians who manage patients with movement disorders. The borderline between functional and organic dystonia is often ambiguous. Patients with functional dystonia are poor responders to pallidal deep brain stimulation (DBS) and are not good candidates for DBS surgery. Thus, if patients with medically refractory dystonia have functional features, they are usually left untreated with DBS surgery. In order to investigate the outcome of functional dystonia in response to pallidal DBS surgery, we retrospectively included five patients with this condition. Their dystonia was diagnosed as organic by dystonia specialists and also as functional according to the Fahn and Williams criteria or the Gupta and Lang Proposed Revisions. Microelectrode recordings in the globus pallidus internus of all patients showed a cell-firing pattern of bursting with interburst intervals, which is considered typical of organic dystonia. Although their clinical course after DBS surgery was incongruent to organic dystonia, the outcome was good. Our results question the possibility to clearly differentiate functional dystonia from organic dystonia. We hypothesized that functional dystonia can coexist with organic dystonia, and that medically intractable dystonia with combined functional and organic features can be successfully treated by DBS surgery. Full article
(This article belongs to the Collection Collection on Clinical Neuroscience)
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Open AccessArticle
Resting EEG, Hair Cortisol and Cognitive Performance in Healthy Older People with Different Perceived Socioeconomic Status
Brain Sci. 2020, 10(9), 635; https://doi.org/10.3390/brainsci10090635 - 15 Sep 2020
Viewed by 871
Abstract
Successful aging depends upon several internal and external factors that influence the overall aging process. Objective and subjective socioeconomic status emerge as potential psychosocial factors in the ethiopathophysiology of aging-related disorders. Presumably, low socioeconomic status can act as a psychosocial stressor that can [...] Read more.
Successful aging depends upon several internal and external factors that influence the overall aging process. Objective and subjective socioeconomic status emerge as potential psychosocial factors in the ethiopathophysiology of aging-related disorders. Presumably, low socioeconomic status can act as a psychosocial stressor that can affect humans’ physiology via psychoneuroendocrine mechanisms, that may, in turn, affect the brain physiology. In resting-state electroencephalography (EEG), excess theta and delta activity has been related to cognitive decline and dementia. The main aim of this study was to analyze the effect of objective and subjective socioeconomic status (SES) on cognition and brain electrical activity through EEG measures. The present research constitutes a cross-sectional study with thirty healthy older adults (61–82 years old) separated into two clusters: high socioeconomic (HS) and low socioeconomic (LS) status; they were evaluated and compared in cognitive terms using the Wechsler Adult Intelligence Scale (WAIS-IV). An EEG at rest was recorded to measure brain activity and, as an indicator of long-term stress exposure, hair cortisol concentrations (HCC) were measured. Our results show that lower SES is related to a worse performance in working memory tasks (p = 0.009), higher delta (p = 0.002) and theta power (p = 0.039), and lower alpha activity (p = 0.028). However, it seems that SES does not significantly affect HCC in this population of healthy older adults. The effects of SES on long-term cortisol exposure, brain electrical activity, and cognitive functions in healthy older people emphasize the role of psychosocial factors in aging from an integrative perspective that will allow us to implement better prevention programs to target cognitive decline in adults. Full article
(This article belongs to the Special Issue The Role of Stress and Glucocorticoids in Learning and Memory)
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Open AccessArticle
Levetiracetam Reduced the Basal Excitability of the Dentate Gyrus without Restoring Impaired Synaptic Plasticity in Rats with Temporal Lobe Epilepsy
Brain Sci. 2020, 10(9), 634; https://doi.org/10.3390/brainsci10090634 - 11 Sep 2020
Viewed by 830
Abstract
Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive [...] Read more.
Temporal lobe epilepsy (TLE), the most common type of focal epilepsy, affects learning and memory; these effects are thought to emerge from changes in synaptic plasticity. Levetiracetam (LEV) is a widely used antiepileptic drug that is also associated with the reversal of cognitive dysfunction. The long-lasting effect of LEV treatment and its participation in synaptic plasticity have not been explored in early chronic epilepsy. Therefore, through the measurement of evoked field potentials, this study aimed to comprehensively identify the alterations in the excitability and the short-term (depression/facilitation) and long-term synaptic plasticity (long-term potentiation, LTP) of the dentate gyrus of the hippocampus in a lithium–pilocarpine rat model of TLE, as well as their possible restoration by LEV (1 week; 300 mg/kg/day). TLE increased the population spike (PS) amplitude (input/output curve); interestingly, LEV treatment partially reduced this hyperexcitability. Furthermore, TLE augmented synaptic depression, suppressed paired-pulse facilitation, and reduced PS-LTP; however, LEV did not alleviate such alterations. Conversely, the excitatory postsynaptic potential (EPSP)-LTP of TLE rats was comparable to that of control rats and was decreased by LEV. LEV caused a long-lasting attenuation of basal hyperexcitability but did not restore impaired synaptic plasticity in the early chronic phase of TLE. Full article
(This article belongs to the Section Molecular and Cellular Neuroscience)
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Open AccessEditorial
Recent Advances and Future Perspectives in the Development of Therapeutic Approaches for Neurodegenerative Diseases
Brain Sci. 2020, 10(9), 633; https://doi.org/10.3390/brainsci10090633 - 11 Sep 2020
Viewed by 921
Abstract
Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD), severely impact the function of neuronal cells in the brain and have devastating consequences on the quality of life of patients and their families [...] Full article
Open AccessArticle
Developing Employment Environments Where Individuals with ASD Thrive: Using Machine Learning to Explore Employer Policies and Practices
Brain Sci. 2020, 10(9), 632; https://doi.org/10.3390/brainsci10090632 - 11 Sep 2020
Cited by 2 | Viewed by 1075
Abstract
An online survey instrument was developed to assess employers’ perspectives on hiring job candidates with Autism Spectrum Disorder (ASD). The investigators used K-means clustering to categorize companies in clusters based on their hiring practices related to individuals with ASD. This methodology allowed the [...] Read more.
An online survey instrument was developed to assess employers’ perspectives on hiring job candidates with Autism Spectrum Disorder (ASD). The investigators used K-means clustering to categorize companies in clusters based on their hiring practices related to individuals with ASD. This methodology allowed the investigators to assess and compare the various factors of businesses that successfully hire employees with ASD versus those that do not. The cluster analysis indicated that company structures, policies and practices, and perceptions, as well as the needs of employers and employees, were important in determining who would successfully hire individuals with ASD. Key areas that require focused policies and practices include recruitment and hiring, training, accessibility and accommodations, and retention and advancement. Full article
(This article belongs to the Special Issue Advances in Autism Research)
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Open AccessReview
Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway
Brain Sci. 2020, 10(9), 631; https://doi.org/10.3390/brainsci10090631 - 11 Sep 2020
Cited by 3 | Viewed by 1486
Abstract
Autism Spectrum Disorder (ASD) etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and the Kynurenine pathway; here we review the nature of these interactions. Pre-natal or neonatal infections [...] Read more.
Autism Spectrum Disorder (ASD) etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and the Kynurenine pathway; here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies have also identified some important polymorphisms in chromosome loci related to the human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates the Kynurenine pathway with an increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in the glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of the Kynurenine branch induces depletion of melatonin and serotonin, worsening ASD symptoms. Thus, in genetically predisposed subjects, aberrant neurodevelopment may derive from a complex interplay between inflammatory processes, mitochondrial dysfunction, oxidative stress and Kynurenine pathway overexpression. To validate this hypothesis a new translational research approach is necessary. Full article
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