Editor's Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to authors, or important in this field. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

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Article

Article
Changes in the Brain Activity and Visual Performance of Patients with Strabismus and Amblyopia after a Compete Cycle of Light Therapy
Brain Sci. 2021, 11(5), 657; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11050657 - 18 May 2021
Abstract
This research assesses the brain activity and visual performance at baseline and after light therapy (LTH), of seventeen patients with strabismus and amblyopia (SA), and eleven healthy controls (HCs) from Querétaro, México. Quantitative electroencephalogram analysis (qEEG) was used to record the brain activity, [...] Read more.
This research assesses the brain activity and visual performance at baseline and after light therapy (LTH), of seventeen patients with strabismus and amblyopia (SA), and eleven healthy controls (HCs) from Querétaro, México. Quantitative electroencephalogram analysis (qEEG) was used to record the brain activity, and clinical metrics such as the visual acuity, angle of deviation, phoria state, stereopsis, and visual fields determined the visual performance. Results showed a constant higher alpha-wave frequency for HCs. Low voltages remained negative for HCs and positive for SA patients across stimulation. After LTH, high voltage increased in SA patients, and decreased in HCs. A second spectral peak, (theta-wave), was exclusively recorded in SA patients, at baseline and after LTH. Positive Spearman correlations for alpha-wave frequency, low and high voltages were only seen in SA patients. Synchronized brain activity was recorded in all SA patients stimulated with filters transmitting light in the blue but not in the red spectrum. Enhancement in the visual performance of SA patients was found, whereas deterioration of the phoria state and a decrease in the amount of stereopsis was seen in HCs. To conclude, only a suffering brain and a visual pathway which needs to be enabled can benefit from LTH. Full article
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Article
Identifying Diurnal Variability of Brain Connectivity Patterns Using Graph Theory
Brain Sci. 2021, 11(1), 111; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11010111 - 16 Jan 2021
Abstract
Significant differences exist in human brain functions affected by time of day and by people’s diurnal preferences (chronotypes) that are rarely considered in brain studies. In the current study, using network neuroscience and resting-state functional MRI (rs-fMRI) data, we examined the effect of [...] Read more.
Significant differences exist in human brain functions affected by time of day and by people’s diurnal preferences (chronotypes) that are rarely considered in brain studies. In the current study, using network neuroscience and resting-state functional MRI (rs-fMRI) data, we examined the effect of both time of day and the individual’s chronotype on whole-brain network organization. In this regard, 62 participants (39 women; mean age: 23.97 ± 3.26 years; half morning- versus half evening-type) were scanned about 1 and 10 h after wake-up time for morning and evening sessions, respectively. We found evidence for a time-of-day effect on connectivity profiles but not for the effect of chronotype. Compared with the morning session, we found relatively higher small-worldness (an index that represents more efficient network organization) in the evening session, which suggests the dominance of sleep inertia over the circadian and homeostatic processes in the first hours after waking. Furthermore, local graph measures were changed, predominantly across the left hemisphere, in areas such as the precentral gyrus, putamen, inferior frontal gyrus (orbital part), inferior temporal gyrus, as well as the bilateral cerebellum. These findings show the variability of the functional neural network architecture during the day and improve our understanding of the role of time of day in resting-state functional networks. Full article
(This article belongs to the Special Issue Recent Advances in Human Brain Connectivity)
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Article
Sensory Processing and Aggressive Behavior in Adults with Autism Spectrum Disorder
Brain Sci. 2021, 11(1), 95; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11010095 - 14 Jan 2021
Cited by 2
Abstract
Autism spectrum disorder (ASD) may be accompanied by aggressive behavior and is associated with sensory processing difficulties. The present study aims to investigate the direct association between sensory processing and aggressive behavior in adults with ASD. A total of 101 Dutch adult participants [...] Read more.
Autism spectrum disorder (ASD) may be accompanied by aggressive behavior and is associated with sensory processing difficulties. The present study aims to investigate the direct association between sensory processing and aggressive behavior in adults with ASD. A total of 101 Dutch adult participants with ASD, treated in outpatient or inpatient facilities, completed the Adolescent/Adult Sensory Profile (AASP), the Reactive-Proactive Aggression Questionnaire (RPQ), and the Aggression Questionnaire—Short Form (AQ-SF). Results revealed that sensory processing difficulties are associated with more aggressive behavior (f2=0.25), more proactive (f2=0.19) and reactive aggression (f2=0.27), more physical (f2=0.08) and verbal aggression (f2=0.13), and more anger (f2=0.20) and hostility (f2=0.12). Evidence was found for an interaction of the neurological threshold and behavioral response on total aggression and hostility. Participants with higher scores in comparison to the norm group in sensory sensitivity had the highest risk of aggressive behavior. In conclusion, clinical practice may benefit from applying detailed diagnostics on sensory processing difficulties when treating aggressive behavior in adults with ASD. Full article
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Article
Brain Connectivity Changes after Osteopathic Manipulative Treatment: A Randomized Manual Placebo-Controlled Trial
Brain Sci. 2020, 10(12), 969; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10120969 - 11 Dec 2020
Cited by 8
Abstract
The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT [...] Read more.
The effects of osteopathic manipulative treatment (OMT) on functional brain connectivity in healthy adults is missing in the literature. To make up for this lack, we applied advanced network analysis methods to analyze resting state functional magnetic resonance imaging (fMRI) data, after OMT and Placebo treatment (P) in 30 healthy asymptomatic young participants randomized into OMT and placebo groups (OMTg; Pg). fMRI brain activity measures, performed before (T0), immediately after (T1) and three days after (T2) OMT or P were used for inferring treatment effects on brain circuit functional organization. Repeated measures ANOVA and post-hoc analysis demonstrated that Right Precentral Gyrus (F (2, 32) = 5.995, p < 0.005) was more influential over the information flow immediately after the OMT, while decreased betweenness centrality in Left Caudate (F (2, 32) = 6.496, p < 0.005) was observable three days after. Clustering coefficient showed a distinct time-point and group effect. At T1, reduced neighborhood connectivity was observed after OMT in the Left Amygdala (L-Amyg) (F (2, 32) = 7.269, p < 0.005) and Left Middle Temporal Gyrus (F (2, 32) = 6.452, p < 0.005), whereas at T2 the L-Amyg and Vermis-III (F (2, 32) = 6.772, p < 0.005) increased functional interactions. Data demonstrated functional connectivity re-arrangement after OMT. Full article
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Article
Behavioural and Emotional Changes during COVID-19 Lockdown in an Italian Paediatric Population with Neurologic and Psychiatric Disorders
Brain Sci. 2020, 10(12), 918; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10120918 - 27 Nov 2020
Cited by 19
Abstract
On 11 March 2020, a national lockdown was imposed by the Italian government to contain the spread of COVID19 disease. This is an observational longitudinal study conducted at Fondazione Stella Maris (FSM), Italy to investigate lockdown-related emotional and behavioural changes in paediatric neuropsychiatric [...] Read more.
On 11 March 2020, a national lockdown was imposed by the Italian government to contain the spread of COVID19 disease. This is an observational longitudinal study conducted at Fondazione Stella Maris (FSM), Italy to investigate lockdown-related emotional and behavioural changes in paediatric neuropsychiatric population. Families having children (1.5–18 years) with neuropsychiatric disorders referred to FSM have been contacted and proposed to fulfil two online questionnaires (General questionnaire and Child Behaviour Check List (CBCL)) to (i) compare (paired two-sample t-tests) the CBCL scores during lockdown with previous ones, and (ii) investigate the influence (multiple linear regression models) of variables such as age, diagnosis grouping (neurological, neurodevelopmental, emotional, and behavioural disorders) and financial hardship. One hundred and forty-one parents fulfilled the questionnaires. Anxiety and somatic problems increased in 1.5–5 years subpopulation, while obsessive-compulsive, post-traumatic and thought problems increased in 6–18 years subpopulation. In the regression models, younger age in the 1.5–5 years subpopulation resulted as “protective” while financial hardship experienced by families during lockdown was related to psychiatric symptoms increasing in the 6–18 years subpopulation. Some considerations, based on first clinical impressions, are provided in text together with comments in relation to previous and emerging literature on the topic. Full article
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Article
High-Intensity Interval Training Improves Cognitive Flexibility in Older Adults
Brain Sci. 2020, 10(11), 796; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10110796 - 29 Oct 2020
Cited by 9
Abstract
Introduction: Regular aerobic exercise is associated with better executive function in older adults. It is unclear if high-intensity-interval-training (HIIT) elicits moderate-intensity continuous training (MICT) or resistance training (RT). We hypothesized that HIIT would augment executive function more than MICT and RT. Methods: Sixty-nine [...] Read more.
Introduction: Regular aerobic exercise is associated with better executive function in older adults. It is unclear if high-intensity-interval-training (HIIT) elicits moderate-intensity continuous training (MICT) or resistance training (RT). We hypothesized that HIIT would augment executive function more than MICT and RT. Methods: Sixty-nine older adults (age: 68 ± 7 years) performed six weeks (three days/week) of HIIT (2 × 20 min bouts alternating between 15 s intervals at 100% of peak power output (PPO) and passive recovery (0% PPO); n = 24), MICT (34 min at 60% PPO; n = 19), or whole-body RT (eight exercise superior improvements in executive function of older adults than moderate-intensity-continuous-training, 2 × 10 repetitions; n = 26). Cardiorespiratory fitness (i.e., V˙O2max) and executive function were assessed before and after each intervention via a progressive maximal cycle ergometer protocol and the Stroop Task, respectively. Results: The V˙O2max findings revealed a significant group by time interaction (p = 0.001) in which all groups improved following training, but HIIT and MICT improved more than RT. From pre- to post-training, no interaction in the naming condition of the Stroop Task was observed (p > 0.10). However, interaction from pre- to post-training by group was observed, and only the HIIT group exhibited a faster reaction time (from 1250 ± 50 to 1100 ± 50 ms; p < 0.001) in switching (cognitive flexibility). Conclusion: Despite similar improvements in cardiorespiratory fitness, HIIT, but not MICT nor RT, enhanced cognitive flexibility in older adults. Exercise programs should consider using HIIT protocols in an effort to combat cognitive decline in older adults. Full article
(This article belongs to the Section Behavioral Neuroscience)
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Article
Neutrophil-to-Lymphocyte Ratio and Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Revascularization
Brain Sci. 2020, 10(11), 771; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10110771 - 23 Oct 2020
Cited by 32
Abstract
Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of [...] Read more.
Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. Methods: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. Results: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55–78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. Conclusions: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization. Full article
Article
A Genotype-Phenotype Study of High-Resolution FMR1 Nucleic Acid and Protein Analyses in Fragile X Patients with Neurobehavioral Assessments
Brain Sci. 2020, 10(10), 694; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10100694 - 30 Sep 2020
Cited by 19
Abstract
Fragile X syndrome (FXS) is caused by silencing of the FMR1 gene, which encodes a protein with a critical role in synaptic plasticity. The molecular abnormality underlying FMR1 silencing, CGG repeat expansion, is well characterized; however, delineation of the pathway from DNA to [...] Read more.
Fragile X syndrome (FXS) is caused by silencing of the FMR1 gene, which encodes a protein with a critical role in synaptic plasticity. The molecular abnormality underlying FMR1 silencing, CGG repeat expansion, is well characterized; however, delineation of the pathway from DNA to RNA to protein using biosamples from well characterized patients with FXS is limited. Since FXS is a common and prototypical genetic disorder associated with intellectual disability (ID) and autism spectrum disorder (ASD), a comprehensive assessment of the FMR1 DNA-RNA-protein pathway and its correlations with the neurobehavioral phenotype is a priority. We applied nine sensitive and quantitative assays evaluating FMR1 DNA, RNA, and FMRP parameters to a reference set of cell lines representing the range of FMR1 expansions. We then used the most informative of these assays on blood and buccal specimens from cohorts of patients with different FMR1 expansions, with emphasis on those with FXS (N = 42 total, N = 31 with FMRP measurements). The group with FMRP data was also evaluated comprehensively in terms of its neurobehavioral profile, which allowed molecular–neurobehavioral correlations. FMR1 CGG repeat expansions, methylation levels, and FMRP levels, in both cell lines and blood samples, were consistent with findings of previous FMR1 genomic and protein studies. They also demonstrated a high level of agreement between blood and buccal specimens. These assays further corroborated previous reports of the relatively high prevalence of methylation mosaicism (slightly over 50% of the samples). Molecular-neurobehavioral correlations confirmed the inverse relationship between overall severity of the FXS phenotype and decrease in FMRP levels (N = 26 males, mean 4.2 ± 3.3 pg FMRP/ng genomic DNA). Other intriguing findings included a significant relationship between the diagnosis of FXS with ASD and two-fold lower levels of FMRP (mean 2.8 ± 1.3 pg FMRP/ng genomic DNA, p = 0.04), in particular observed in younger age- and IQ-adjusted males (mean age 6.9 ± 0.9 years with mean 3.2 ± 1.2 pg FMRP/ng genomic DNA, 57% with severe ASD), compared to FXS without ASD. Those with severe ID had even lower FMRP levels independent of ASD status in the male-only subset. The results underscore the link between FMR1 expansion, gene methylation, and FMRP deficit. The association between FMRP deficiency and overall severity of the neurobehavioral phenotype invites follow up studies in larger patient cohorts. They would be valuable to confirm and potentially extend our initial findings of the relationship between ASD and other neurobehavioral features and the magnitude of FMRP deficit. Molecular profiling of individuals with FXS may have important implications in research and clinical practice. Full article
(This article belongs to the Special Issue Update on the Treatment of Fragile X Syndrome)
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Article
Tele-Assisted Behavioral Intervention for Families with Children with Autism Spectrum Disorders: A Randomized Control Trial
Brain Sci. 2020, 10(9), 649; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10090649 - 18 Sep 2020
Cited by 10
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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Article
Using Plasma Autoantibodies of Central Nervous System Proteins to Distinguish Veterans with Gulf War Illness from Healthy and Symptomatic Controls
Brain Sci. 2020, 10(9), 610; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10090610 - 05 Sep 2020
Cited by 10
Abstract
For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported [...] Read more.
For the past 30 years, there has been a lack of objective tools for diagnosing Gulf War Illness (GWI), which is largely characterized by central nervous system (CNS) symptoms emerging from 1991 Gulf War (GW) veterans. In a recent preliminary study, we reported the presence of autoantibodies against CNS proteins in the blood of veterans with GWI, suggesting a potential objective biomarker for the disorder. Now, we report the results of a larger, confirmatory study of these objective biomarkers in 171 veterans with GWI compared to 60 healthy GW veteran controls and 85 symptomatic civilian controls (n = 50 myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and n = 35 irritable bowel syndrome (IBS)). Specifically, we compared plasma markers of CNS autoantibodies for diagnostic characteristics of the four groups (GWI, GW controls, ME/CFS, IBS). For veterans with GWI, the results showed statistically increased levels of nine of the ten autoantibodies against neuronal “tubulin, neurofilament protein (NFP), Microtubule Associated Protein-2 (MAP-2), Microtubule Associated Protein-Tau (Tau), alpha synuclein (α-syn), calcium calmodulin kinase II (CaMKII)” and glial proteins “Glial Fibrillary Acidic Protein (GFAP), Myelin Associated Glycoprotein (MAG), Myelin Basic Protein (MBP), S100B” compared to healthy GW controls as well as civilians with ME/CFS and IBS. Next, we summed all of the means of the CNS autoantibodies for each group into a new index score called the Neurodegeneration Index (NDI). The NDI was calculated for each tested group and showed veterans with GWI had statistically significantly higher NDI values than all three control groups. The present study confirmed the utility of the use of plasma autoantibodies for CNS proteins to distinguish among veterans with GWI and other healthy and symptomatic control groups. Full article
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Article
Allocentric Spatial Memory Performance in a Virtual Reality-Based Task is Conditioned by Visuospatial Working Memory Capacity
Brain Sci. 2020, 10(8), 552; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10080552 - 13 Aug 2020
Cited by 7
Abstract
Traditionally, the medial temporal lobe has been considered a key brain region for spatial memory. Nevertheless, executive functions, such as working memory, also play an important role in complex behaviors, such as spatial navigation. Thus, the main goal of this study is to [...] Read more.
Traditionally, the medial temporal lobe has been considered a key brain region for spatial memory. Nevertheless, executive functions, such as working memory, also play an important role in complex behaviors, such as spatial navigation. Thus, the main goal of this study is to clarify the relationship between working memory capacity and spatial memory performance. Spatial memory was assessed using a virtual reality-based procedure, the Boxes Room task, and the visual working memory with the computer-based Change Localization Task. One hundred and twenty-three (n = 123) participants took part in this study. Analysis of Covariance (ANCOVA) revealed a statistically significant relationship between working memory capacity and spatial abilities. Thereafter, two subgroups n = 60, were formed according to their performance in the working memory task (1st and 4th quartiles, n = 30 each). Results demonstrate that participants with high working memory capacity committed fewer mistakes in the spatial task compared to the low working memory capacity group. Both groups improved their performance through repeated trials of the spatial task, thus showing that they could learn spatial layouts independent of their working memory capacity. In conclusion, these findings support that spatial memory performance is directly related to working memory skills. This could be relevant for spatial memory assessment in brain lesioned patients. Full article
(This article belongs to the Special Issue Effects of Individual Differences on Spatial Cognition)
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Article
TLR Antagonism by Sparstolonin B Alters Microbial Signature and Modulates Gastrointestinal and Neuronal Inflammation in Gulf War Illness Preclinical Model
Brain Sci. 2020, 10(8), 532; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10080532 - 08 Aug 2020
Cited by 8
Abstract
The 1991 Persian Gulf War veterans presented a myriad of symptoms that ranged from chronic pain, fatigue, gastrointestinal disturbances, and cognitive deficits. Currently, no therapeutic regimen exists to treat the plethora of chronic symptoms though newer pharmacological targets such as microbiome have been [...] Read more.
The 1991 Persian Gulf War veterans presented a myriad of symptoms that ranged from chronic pain, fatigue, gastrointestinal disturbances, and cognitive deficits. Currently, no therapeutic regimen exists to treat the plethora of chronic symptoms though newer pharmacological targets such as microbiome have been identified recently. Toll-like receptor 4 (TLR4) antagonism in systemic inflammatory diseases have been tried before with limited success, but strategies with broad-spectrum TLR4 antagonists and their ability to modulate the host-microbiome have been elusive. Using a mouse model of Gulf War Illness, we show that a nutraceutical, derived from a Chinese herb Sparstolonin B (SsnB) presented a unique microbiome signature with an increased abundance of butyrogenic bacteria. SsnB administration restored a normal tight junction protein profile with an increase in Occludin and a parallel decrease in Claudin 2 and inflammatory mediators high mobility group box 1 (HMGB1), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the distal intestine. SsnB also decreased neuronal inflammation by decreasing IL-1β and HMGB1, while increasing brain-derived neurotrophic factor (BDNF), with a parallel decrease in astrocyte activation in vitro. Mechanistically, SsnB inhibited the binding of HMGB1 and myeloid differentiation primary response protein (MyD88) to TLR4 in the intestine, thus attenuating TLR4 downstream signaling. Studies also showed that SsnB was effective in suppressing TLR4-induced nod-like receptor protein 3 (NLRP3) inflammasome activation, a prominent inflammatory disease pathway. SsnB significantly decreased astrocyte activation by decreasing colocalization of glial fibrillary acid protein (GFAP) and S100 calcium-binding protein B (S100B), a crucial event in neuronal inflammation. Inactivation of SsnB by treating the parent molecule by acetate reversed the deactivation of NLRP3 inflammasome and astrocytes in vitro, suggesting that SsnB molecular motifs may be responsible for its anti-inflammatory activity. Full article
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Communication
Effective Strategies for Managing COVID-19 Emergency Restrictions for Adults with Severe ASD in a Daycare Center in Italy
Brain Sci. 2020, 10(7), 436; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10070436 - 09 Jul 2020
Cited by 10
Abstract
The COVID-19 pandemic has posed a serious challenge for the life and mental health of people with autism spectrum disorder (ASD). COVID-19 sanitary restrictions led to significant changes in the lives of people with ASD, including their routines; similarly, these modifications affected the [...] Read more.
The COVID-19 pandemic has posed a serious challenge for the life and mental health of people with autism spectrum disorder (ASD). COVID-19 sanitary restrictions led to significant changes in the lives of people with ASD, including their routines; similarly, these modifications affected the daily activities of the daycare centers which they attended. The present retrospective study evaluated the impact of COVID-19 restrictions on challenging behaviors in a cohort of people with severe ASD attending a daycare center in Italy at the beginning of the pandemic. During the first two weeks of the pandemic, we did not observe variations in challenging behaviors. This suggests that adaptations used to support these individuals with ASD in adapting to the COVID-19 emergency restrictions were effective for managing their behavior. Full article
(This article belongs to the Special Issue Advances in Autism Research)
Article
Uniportal Full Endoscopic Posterolateral Transforaminal Lumbar Interbody Fusion with Endoscopic Disc Drilling Preparation Technique for Symptomatic Foraminal Stenosis Secondary to Severe Collapsed Disc Space: A Clinical and Computer Tomographic Study with Technical Note
Brain Sci. 2020, 10(6), 373; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10060373 - 15 Jun 2020
Cited by 11
Abstract
Background: Severe collapsed disc secondary to degenerative spinal conditions leads to significant foraminal stenosis. We hypothesized that uniportal posterolateral transforaminal lumbar interbody fusion with endoscopic disc drilling technique could be safely applied to the collapsed disc space to improve patients’ pain score, restore [...] Read more.
Background: Severe collapsed disc secondary to degenerative spinal conditions leads to significant foraminal stenosis. We hypothesized that uniportal posterolateral transforaminal lumbar interbody fusion with endoscopic disc drilling technique could be safely applied to the collapsed disc space to improve patients’ pain score, restore disc height, and correct the segmental angular parameters. Methods: We included patients who met the indication criteria for lumbar fusion and underwent uniportal full endoscopic posterolateral transforaminal lumbar interbody fusion with pre-operative Computer Tomography mid disc height of less than or equal to 5 mm and MRI of Grade 3 Foraminal Stenosis. Visual analogue scale and computer tomography pre-operative and post-operative sagittal disc height in the anterior, middle and posterior part of the disc; sagittal focal segmental angle; mid coronal disc height and coronal wedge angles were evaluated. Results: 30 levels of Endo-TLIF were included, with a mean follow up of 12 months. The mean improvement in decreasing pain score was 2.5 ± 1.1, 3.2 ± 0.9 and 4.3 ± 1.0 at 1 week post operation, 3 months post operation and at final follow up, respectively, p < 0.05. There was significant increase in mid sagittal computer tomographic anterior, middle and posterior disc height of 6.99 ± 2.30, 6.28 ± 1.44, 5.12 ± 1.79 mm respectively, p < 0.05. CT mid coronal disc height showed an increase of 7.13 ± 1.90 mm, p < 0.05. There was a significant improvement in the CT coronal wedge angle of 2.35 ± 4.73 and the CT segmental focal sagittal angle of 1.98 ± 4.69, p < 0.05. Conclusion: Application of Uniportal Endoscopic Posterolateral Lumbar Interbody Fusion in patients with severe foraminal stenosis secondary to severe collapsed disc space significantly relieved patients’ pain and restored disc height without early subsidence or exiting nerve root dysesthesia in our cohort of patients. Full article
(This article belongs to the Special Issue Degenerative Spinal Disease)
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Article
Psychosocial and Behavioral Impact of COVID-19 in Autism Spectrum Disorder: An Online Parent Survey
Brain Sci. 2020, 10(6), 341; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10060341 - 03 Jun 2020
Cited by 113
Abstract
The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. [...] Read more.
The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42–3.29) and more frequent (OR = 1.67, 95% CI 1.13–2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals. Full article
(This article belongs to the Special Issue Advances in Autism Research)
Article
The Neuropsychological Profile of Attention Deficits of Patients with Obstructive Sleep Apnea: An Update on the Daytime Attentional Impairment
Brain Sci. 2020, 10(6), 325; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10060325 - 27 May 2020
Cited by 7
Abstract
Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim [...] Read more.
Introduction: Patients with obstructive sleep apnea (OSA) suffer from several neurocognitive disturbances. One of the neuropsychological processes most investigated in OSA patients is attention, but the results have been controversial. Here, we update the attention profile of OSA patients with the final aim to improve attention assessment, with a possible impact on clinical and medical-legal practices, in terms of which attention subdomains and parameters need consideration and which one is a high-risk OSA phenotype for attention dysfunctions. Method: For this purpose, we assessed 32 previously untreated OSA patients (26 men and 6 women) under 65 years of age (mean age 53.2 ± 7.3; mean education level 10.4 ± 3.4 years) suffering from moderate to severe sleep apnea and hypopnea (mean apnea-hypopnea index (AHI) 45.3 ± 22.9, range 16.1–69.6). A control group of 34 healthy participants matched with OSA patients for age, education level, and general cognitive functioning were also enrolled. The OSA patients and healthy participants were tested through an extensive computerized battery (Test of Attentional Performance, TAP) that evaluated intensive (i.e., alertness and vigilance) and selective (i.e., divided and selective) dimensions of attention and returned different outcome parameters (i.e., reaction time, stability of performance, and various types of errors). Data analysis: The data were analyzed by ANCOVA which compared the speed and accuracy performance of the OSA and control participants (cognitive reserve was treated as a covariate). The possible mechanisms underlying attention deficits in OSA patients were examined through correlation analysis among AHI, oxygenation parameters, sleepiness scores, and TAP outcomes and by comparing the following three phenotypes of patients: severe OSA and severe nocturnal desaturators (AHI++D+), severe OSA nondesaturators (AHI++D), and moderate OSA nondesaturators (AHI+D). Results: The results suggest that the OSA patients manifest deficits in both intensive and selective attention processes and that reaction time (RT) alone is ineffective for detecting and characterizing their problems, for which error analysis and stability of performance also have to be considered. Patients with severe OSA and severe hypoxemia underperformed on alertness and vigilance attention subtests. Conclusions: The data suggest the importance of evaluating attention deficits among OSA patients through several parameters (including performance instability). Moreover, the data suggest a multifaceted mechanism underlying attention dysfunction in OSA patients. Full article
(This article belongs to the Special Issue Effects of Sleep Disruption on Daytime Functioning)
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Article
Probiotics Alleviate the Progressive Deterioration of Motor Functions in a Mouse Model of Parkinson’s Disease
Brain Sci. 2020, 10(4), 206; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10040206 - 01 Apr 2020
Cited by 27
Abstract
Parkinson’s disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present before motor symptoms. It has been found that gut dysbiosis to PD pathology is related [...] Read more.
Parkinson’s disease (PD) is one of the common long-term degenerative disorders that primarily affect motor systems. Gastrointestinal (GI) symptoms are common in individuals with PD and often present before motor symptoms. It has been found that gut dysbiosis to PD pathology is related to the severity of motor and non-motor symptoms in PD. Probiotics have been reported to have the ability to improve the symptoms related to constipation in PD patients. However, the evidence from preclinical or clinical research to verify the beneficial effects of probiotics for the motor functions in PD is still limited. An experimental PD animal model could be helpful in exploring the potential therapeutic strategy using probiotics. In the current study, we examined whether daily and long-term administration of probiotics has neuroprotective effects on nigrostriatal dopamine neurons and whether it can further alleviate the motor dysfunctions in PD mice. Transgenic MitoPark PD mice were chosen for this study and the effects of daily probiotic treatment on gait, beam balance, motor coordination, and the degeneration levels of dopaminergic neurons were identified. From the results, compared with the sham treatment group, we found that the daily administration of probiotics significantly reduced the motor impairments in gait pattern, balance function, and motor coordination. Immunohistochemically, a tyrosine hydroxylase (TH)-positive cell in the substantia nigra was significantly preserved in the probiotic-treated PD mice. These results showed that long-term administration of probiotics has neuroprotective effects on dopamine neurons and further attenuates the deterioration of motor dysfunctions in MitoPark PD mice. Our data further highlighted the promising possibility of the potential use of probiotics, which could be the relevant approach for further application on human PD subjects. Full article
(This article belongs to the Special Issue Brain–Microbiome Interactions)
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Article
Association between Exposure to Air Pollution and Total Gray Matter and Total White Matter Volumes in Adults: A Cross-Sectional Study
Brain Sci. 2020, 10(3), 164; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10030164 - 13 Mar 2020
Cited by 10
Abstract
Total brain gray-matter and white-matter volumes can be indicators of overall brain health. Among the factors associated with gray-matter and white-matter volumes is exposure to air pollution. Using data from the UK Biobank, we sought to determine associations between several components of air [...] Read more.
Total brain gray-matter and white-matter volumes can be indicators of overall brain health. Among the factors associated with gray-matter and white-matter volumes is exposure to air pollution. Using data from the UK Biobank, we sought to determine associations between several components of air pollution—PM2.5, PM2.5–10, PM10, nitrogen dioxide, and nitrogen oxides—and total gray-matter and total white-matter volumes in multivariable regression models in a large sample of adults. We found significant inverse associations between PM2.5 concentration and total white-matter volume and between PM2.5, PM2.5–10, PM10, nitrogen dioxide, and nitrogen oxide concentrations and total gray-matter volume in models adjusted for age, sex, body-mass index, self-assessment of overall health, frequency of alcohol use, smoking status, educational attainment, and income. These findings of pollutant-associated decreases in total gray-matter and total white-matter volumes are in the context of mean PM2.5 concentrations near the upper limit of the World Health Organization’s recommendations. Similarly, mean PM10 concentrations were below the recommended upper limit, and nitrogen dioxide concentration was slightly above. Still, there are many areas in the world with much higher concentrations of these pollutants, which could be associated with larger effects. If replicated, these findings suggest that air pollution could be a risk factor for neurodegeneration. Full article
Article
Leg Dominance Effects on Postural Control When Performing Challenging Balance Exercises
Brain Sci. 2020, 10(3), 128; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10030128 - 25 Feb 2020
Cited by 13
Abstract
Leg dominance reflects the preferential use of one leg over another and is typically attributed to asymmetries in the neural circuitry. Detecting leg dominance effects on motor behavior, particularly during balancing exercises, has proven difficult. The current study applied a principal component analysis [...] Read more.
Leg dominance reflects the preferential use of one leg over another and is typically attributed to asymmetries in the neural circuitry. Detecting leg dominance effects on motor behavior, particularly during balancing exercises, has proven difficult. The current study applied a principal component analysis (PCA) on kinematic data, to assess bilateral asymmetry on the coordinative structure (hypothesis H1) or on the control characteristics of specific movement components (hypothesis H2). Marker-based motion tracking was performed on 26 healthy adults (aged 25.3 ± 4.1 years), who stood unipedally on a multiaxial unstable board, in a randomized order, on their dominant and non-dominant leg. Leg dominance was defined as the kicking leg. PCA was performed to determine patterns of correlated segment movements (“principal movements” PMks). The control of each PMk was characterized by assessing its acceleration (second-time derivative). Results were inconclusive regarding a leg-dominance effect on the coordinative structure of balancing movements (H1 inconclusive); however, different control (p = 0.005) was observed in PM3, representing a diagonal plane movement component (H2 was supported). These findings supported that leg dominance effects should be considered when assessing or training lower-limb neuromuscular control and suggest that specific attention should be given to diagonal plane movements. Full article
(This article belongs to the Collection Collection on Systems Neuroscience)
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Article
Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in Mice
Brain Sci. 2020, 10(2), 126; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020126 - 23 Feb 2020
Cited by 14
Abstract
Probiotic bacteria have beneficial effects to the development and maintenance of a healthy microflora that subsequently has health benefits to humans. Some of the health benefits attributed to probiotics have been noted to be via their immune modulatory properties suppressing inflammatory conditions. Hence, [...] Read more.
Probiotic bacteria have beneficial effects to the development and maintenance of a healthy microflora that subsequently has health benefits to humans. Some of the health benefits attributed to probiotics have been noted to be via their immune modulatory properties suppressing inflammatory conditions. Hence, probiotics have become prominent in recent years of investigation with regard to their health benefits. As such, in the current study, we determined the effects of Streptococcus thermophilus to agonist MBP83–99 peptide immunized mouse spleen cells. It was noted that Streptococcus thermophilus induced a significant increase in the expression of anti-inflammatory IL-4, IL-5, IL-10 cytokines, and decreased the secretion of pro-inflammatory IL-1β and IFN-γ. Regular consumption of Streptococcus thermophilus may therefore be beneficial in the management and treatment of autoimmune diseases such as multiple sclerosis. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis Research—Series I)
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Article
Beneficial Effect of Foot Plantar Stimulation in Gait Parameters in Individuals with Parkinson’s Disease
Brain Sci. 2020, 10(2), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020069 - 27 Jan 2020
Cited by 15
Abstract
New treatments based on peripheral stimulation of the sensory-motor system have shown to be promising in rehabilitation strategies for patients with neurological disorders, including Parkinson’s disease (PD), especially in regards to reducing gait impairment, and hence, the incidence of falls. The aim of [...] Read more.
New treatments based on peripheral stimulation of the sensory-motor system have shown to be promising in rehabilitation strategies for patients with neurological disorders, including Parkinson’s disease (PD), especially in regards to reducing gait impairment, and hence, the incidence of falls. The aim of this study was to evaluate the change in several gait parameters measured by sensor inertial measurement in PD patients after acute plantar stimulation, under the distal phalanx of the big toe, and underneath the head of the first metatarsal joint of both feet, using a 3D printing insole. In order to assess whether the effects are selective for PD patients, we compared the effect of the treatment in a control group (age-matched) consisting of patients with other neurological disorders which also displayed gait and balance impairment, and a similar cognitive function, depressive symptoms, body mass index, and comorbidity burden observed in the PD group. Plantar foot stimulation in PD patients eliminated the significant (p < 0.05) alterations existing in stride asymmetry and in stride variability. When comparing the effects of post-plantar stimulation with the respective basal level, considered as 100% in both groups, we observed a significant (p = 0.019, Mann–Whitney test) increase in stride length compared to basal in the PD group and control group. No significant effects of foot plantar stimulation were observed in any of the gait parameters in the control group. Plantar foot stimulation has a positive effect on the step and stride length, and has a positive effect on walking stability, measured by the increase in stride length. No significant effect was observed on bradykinesia because it did not improve walking velocity. These findings indicate that foot plantar stimulation using a 3D printing insole seems to generate a more stable walking pattern in PD patients, with an interesting applicability, and a low-cost, for reducing gait impairment in PD patients. Full article
(This article belongs to the Special Issue Frontiers in Parkinson’s Disease (PD))
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Article
The Relationship between Expressive Language Sampling and Clinical Measures in Fragile X Syndrome and Typical Development
Brain Sci. 2020, 10(2), 66; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020066 - 26 Jan 2020
Cited by 8
Abstract
Language impairment is a core difficulty in fragile X syndrome (FXS), and yet standardized measures lack the sensitivity to assess developmental changes in the nature of these impairments. Expressive Language Sampling Narrative (ELS-N) has emerged as a promising new measure with research demonstrating [...] Read more.
Language impairment is a core difficulty in fragile X syndrome (FXS), and yet standardized measures lack the sensitivity to assess developmental changes in the nature of these impairments. Expressive Language Sampling Narrative (ELS-N) has emerged as a promising new measure with research demonstrating its usefulness in a wide range of ages in developmental disabilities and typical development. We examined ELS-N results in FXS and age-matched typically developing (TD) controls along with cognitive, adaptive, and clinical measures. We found the groups differed significantly on all ELS-N variables. Cognitive abilities were related to lexical diversity, syntactic complexity, and unintelligibility for the FXS group, but only verbal abilities were related to syntactic complexity in TD. Autism spectrum disorder (ASD) symptomatology was related to less intelligibility in speech. Measures of hyperactivity were related to increased talkativeness and unintelligibility. In addition, FXS males in comparison to FXS females were more impaired in cognitive ability, ASD symptoms, hyperactivity, and anxiety. This study extends the previous ELS research, supporting its use in FXS research as a measure to characterize language abilities. It also demonstrates the relationships between ELS-N variables and measures of cognitive, adaptive, ASD symptoms, and clinical symptoms. Full article
(This article belongs to the Special Issue Update on the Treatment of Fragile X Syndrome)
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Article
The Role of Emotional Landmarks in Embodied and Not-Embodied Tasks
Brain Sci. 2020, 10(2), 58; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10020058 - 21 Jan 2020
Cited by 9
Abstract
The role of emotional landmarks in navigation has been scarcely studied. Previous findings showed that valence and arousal of landmarks increase landmark’s salience and improve performance in navigational memory tasks. However, no study has directly explored the interplay between valence and arousal of [...] Read more.
The role of emotional landmarks in navigation has been scarcely studied. Previous findings showed that valence and arousal of landmarks increase landmark’s salience and improve performance in navigational memory tasks. However, no study has directly explored the interplay between valence and arousal of emotionally laden landmarks in embodied and not-embodied navigational tasks. At the aim, 115 college students have been subdivided in five groups according to the landmarks they were exposed (High Positive Landmarks HPL; Low Positive Landmarks LPL; High Negative Landmarks HNL; Low Negative Landmarks LNL and Neutral Landmarks NeuL). In the embodied tasks participants were asked to learn a path in a first-person perspective and to recall it after five minutes, whereas in the not-embodied tasks participants were asked to track the learned path on a silent map and to recognize landmarks among distractors. Results highlighted firstly the key role of valence in the embodied task related to the immediate learning, but not to the delayed recall of the path, probably because of the short retention interval used. Secondly, results showed the importance of the interplay between valence and arousal in the non-embodied tasks, specifically, neutral and high negative emotional landmarks yielded the lowest performance probably because of the avoidance learning effect. Implications for future research directions are discussed. Full article
(This article belongs to the Special Issue The Role of Body in Brain Plasticity)
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Article
Inhibitory Effects of Myricetin on Lipopolysaccharide-Induced Neuroinflammation
Brain Sci. 2020, 10(1), 32; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10010032 - 06 Jan 2020
Cited by 12
Abstract
Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. [...] Read more.
Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. However, whether myricetin inhibits lipopolysaccharide (LPS)-induced neuroinflammation in hippocampus and cortex regions is not known. To test this, we examined the effects of myricetin on LPS-induced neuroinflammation in a microglial BV2 cell line. We found that myricetin significantly downregulated several markers of the neuroinflammatory response in LPS-induced activated microglia, including inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory modulators and cytokines such as prostaglandin E2 (PGE2), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Moreover, myricetin suppressed the expression of c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, myricetin inhibited LPS-induced macrophages and microglial activation in the hippocampus and cortex of mice. Based on our results, we suggest that myricetin inhibits neuroinflammation in BV2 microglia by inhibiting the MAPK signaling pathway and the production of proinflammatory modulators and cytokines. Therefore, this could potentially be used for the treatment of neuroinflammatory diseases. Full article
(This article belongs to the Section Neuroglia)
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Article
The Tolerability and Efficacy of 4 mA Transcranial Direct Current Stimulation on Leg Muscle Fatigability
Brain Sci. 2020, 10(1), 12; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10010012 - 23 Dec 2019
Cited by 15
Abstract
Transcranial direct current stimulation (tDCS) modulates cortical excitability and affects a variety of outcomes. tDCS at intensities ≤2 mA is well-tolerated, but the tolerability and efficacy of tDCS at intensities >2 mA merits systematic investigation. The study objective was to determine the tolerability [...] Read more.
Transcranial direct current stimulation (tDCS) modulates cortical excitability and affects a variety of outcomes. tDCS at intensities ≤2 mA is well-tolerated, but the tolerability and efficacy of tDCS at intensities >2 mA merits systematic investigation. The study objective was to determine the tolerability and effects of 4 mA tDCS on leg muscle fatigability. Thirty-one young, healthy adults underwent two randomly ordered tDCS conditions (sham, 4 mA) applied before and during an isokinetic fatigue test of the knee extensors and flexors. Subjects reported the severity of the sensations felt from tDCS. Primary outcomes were sensation tolerability and the fatigue index of the knee extensors and flexors. A repeated-measures ANOVA determined statistical significance (p < 0.05). Sensation severity at 4 mA tDCS was not substantially different than sham. However, two subjects reported a moderate–severe headache, which dissipated soon after the stimulation ended. The left knee flexors had significantly greater fatigability with 4 mA tDCS compared with sham (p = 0.018). tDCS at 4 mA was well-tolerated by young, healthy subjects and increased left knee flexor fatigability. Exploration of higher intensity tDCS (>2 mA) to determine the potential benefits of increasing intensity, especially in clinical populations with decreased brain activity/excitability, is warranted. Full article
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Article
Should the Minimal Intervention Principle Be Considered When Investigating Dual-Tasking Effects on Postural Control?
Brain Sci. 2020, 10(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10010001 - 19 Dec 2019
Cited by 12
Abstract
Dual-tasking charges the sensorimotor system with performing two tasks simultaneously. Center of pressure (COP) analysis reveals the postural control that is altered during dual-tasking, but may not reveal the underlying neural mechanisms. In the current study, we hypothesized that the minimal intervention principle [...] Read more.
Dual-tasking charges the sensorimotor system with performing two tasks simultaneously. Center of pressure (COP) analysis reveals the postural control that is altered during dual-tasking, but may not reveal the underlying neural mechanisms. In the current study, we hypothesized that the minimal intervention principle (MIP) provides a concept by which dual-tasking effects on the organization and prioritization of postural control can be predicted. Postural movements of 23 adolescents (age 12.7 ± 1.3; 8 females) and 15 adults (26.9 ± 2.3) were measured in a bipedal stance with eyes open, eyes closed and eyes open while performing a dual-task using a force plate and 39 reflective markers. COP data was analyzed by calculating the mean velocity, standard deviation and amplitude of displacement. Kinematic data was examined by performing a principal component analysis (PCA) and extracting postural movement components. Two variables were determined to investigate changes in amplitude (aVark) and in control (Nk) of the principal movement components. Results in aVark and in Nk agreed well with the predicted dual-tasking effects. Thus, the current study corroborates the notion that the MIP should be considered when investigating postural control under dual-tasking conditions. Full article
(This article belongs to the Collection Collection on Systems Neuroscience)
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Article
A Hybrid Feature Pool-Based Emotional Stress State Detection Algorithm Using EEG Signals
Brain Sci. 2019, 9(12), 376; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9120376 - 13 Dec 2019
Cited by 10
Abstract
Human stress analysis using electroencephalogram (EEG) signals requires a detailed and domain-specific information pool to develop an effective machine learning model. In this study, a multi-domain hybrid feature pool is designed to identify most of the important information from the signal. The hybrid [...] Read more.
Human stress analysis using electroencephalogram (EEG) signals requires a detailed and domain-specific information pool to develop an effective machine learning model. In this study, a multi-domain hybrid feature pool is designed to identify most of the important information from the signal. The hybrid feature pool contains features from two types of analysis: (a) statistical parametric analysis from the time domain, and (b) wavelet-based bandwidth specific feature analysis from the time-frequency domain. Then, a wrapper-based feature selector, Boruta, is applied for ranking all the relevant features from that feature pool instead of considering only the non-redundant features. Finally, the k-nearest neighbor (k-NN) algorithm is used for final classification. The proposed model yields an overall accuracy of 73.38% for the total considered dataset. To validate the performance of the proposed model and highlight the necessity of designing a hybrid feature pool, the model was compared to non-linear dimensionality reduction techniques, as well as those without feature ranking. Full article
(This article belongs to the Special Issue Brain Plasticity, Cognitive Training and Mental States Assessment)
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Article
Functional Connectivity between the Resting-State Olfactory Network and the Hippocampus in Alzheimer’s Disease
Brain Sci. 2019, 9(12), 338; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9120338 - 25 Nov 2019
Cited by 13
Abstract
Olfactory impairment is associated with prodromal Alzheimer’s disease (AD) and is a risk factor for the development of dementia. AD pathology is known to disrupt brain regions instrumental in olfactory information processing, such as the primary olfactory cortex (POC), the hippocampus, and other [...] Read more.
Olfactory impairment is associated with prodromal Alzheimer’s disease (AD) and is a risk factor for the development of dementia. AD pathology is known to disrupt brain regions instrumental in olfactory information processing, such as the primary olfactory cortex (POC), the hippocampus, and other temporal lobe structures. This selective vulnerability suggests that the functional connectivity (FC) between the olfactory network (ON), consisting of the POC, insula and orbital frontal cortex (OFC) (Tobia et al., 2016), and the hippocampus may be impaired in early stage AD. Yet, the development trajectory of this potential FC impairment remains unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to investigate FC changes between the ON and hippocampus in four groups: aged-matched cognitively normal (CN), early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI), and AD. FC was calculated using low frequency fMRI signal fluctuations in the ON and hippocampus (Tobia et al., 2016). We found that the FC between the ON and the right hippocampus became progressively disrupted across disease states, with significant differences between EMCI and LMCI groups. Additionally, there were no significant differences in gray matter hippocampal volumes between EMCI and LMCI groups. Lastly, the FC between the ON and hippocampus was significantly correlated with neuropsychological test scores, suggesting that it is related to cognition in a meaningful way. These findings provide the first in vivo evidence for the involvement of FC between the ON and hippocampus in AD pathology. Results suggest that functional connectivity (FC) between the olfactory network (ON) and hippocampus may be a sensitive marker for Alzheimer’s disease (AD) progression, preceding gray matter volume loss. Full article
(This article belongs to the Special Issue Olfaction as a Marker for Psychiatric and Neurological Diseases)
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Article
Lost in Classification: Lower Cognitive Functioning in Apparently Cognitive Normal Newly Diagnosed RRMS Patients
Brain Sci. 2019, 9(11), 321; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9110321 - 13 Nov 2019
Cited by 11
Abstract
Cognitive functioning in multiple sclerosis (MS) patients is usually related to the classic, dichotomic classification of impaired vs. unimpaired cognition. However, this approach is far from mirroring the real efficiency of cognitive functioning. Applying a different approach in which cognitive functioning is considered [...] Read more.
Cognitive functioning in multiple sclerosis (MS) patients is usually related to the classic, dichotomic classification of impaired vs. unimpaired cognition. However, this approach is far from mirroring the real efficiency of cognitive functioning. Applying a different approach in which cognitive functioning is considered as a continuous variable, we aimed at showing that even newly diagnosed relapsing–remitting MS (RRMS) patients might suffer from reduced cognitive functioning with respect to a matched group of neurologically healthy controls (HCs), even if they were classified as having no cognitive impairment (CI). Fifty newly diagnosed RRMS patients and 36 HCs were tested with an extensive battery of neuropsychological tests. By using Z-scores applied to the whole group of RRMS and HCs together, a measure of cognitive functioning (Z-score index) was calculated. Among the 50 RRMS patients tested, 36 were classified as cognitively normal (CN). Even though classified as CN, RRMS patients performed worse than HCs at a global level (p = 0.004) and, more specifically, in the domains of memory (p = 0.005) and executive functioning (p = 0.006). These results highlight that reduced cognitive functioning can be present early in the disease course, even in patients without an evident CI. The current classification criteria of CI in MS should be considered with caution. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis Research—Series I)
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Article
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://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9100284 - 19 Oct 2019
Cited by 18
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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Article
The Role of the Embodiment Disturbance in the Anorexia Nervosa Psychopathology: A Network Analysis Study
Brain Sci. 2019, 9(10), 276; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9100276 - 15 Oct 2019
Cited by 19
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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Article
A Comprehensive Examination of Percutaneous Endoscopic Gastrostomy and Its Association with Amyotrophic Lateral Sclerosis Patient Outcomes
Brain Sci. 2019, 9(9), 223; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9090223 - 04 Sep 2019
Cited by 14
Abstract
There is literature discord regarding the impact of percutaneous endoscopic gastrostomy (PEG), or “feeding tube”, on amyotrophic lateral sclerosis (ALS) outcomes. We assess one of the largest retrospective ALS cohorts to date (278 PEG users, 679 non-users). Kruskal–Wallis and Kaplan–Meier analysis compared cohort [...] Read more.
There is literature discord regarding the impact of percutaneous endoscopic gastrostomy (PEG), or “feeding tube”, on amyotrophic lateral sclerosis (ALS) outcomes. We assess one of the largest retrospective ALS cohorts to date (278 PEG users, 679 non-users). Kruskal–Wallis and Kaplan–Meier analysis compared cohort medians and survival duration trends. A meta-analysis determined the aggregate associative effect of PEG on survival duration by combining primary results with 7 published studies. Primary results (p < 0.001) and meta-analysis (p < 0.05) showed PEG usage is associated with an overall significant increase in ALS survival duration, regardless of onset type. Percent predicted forced vital capacity (FVC %predict) ≥50 at PEG insertion significantly increases survival duration (p < 0.001); FVC %predict ≥60 has the largest associative benefit (+6.7 months, p < 0.05). Time elapsed from ALS onset until PEG placement is not predictive (p > 0.05). ALSFRS-R survey assessment illustrates PEG usage does not slow functional ALS pathology (p > 0.05), but does stabilize weight and/or body mass index (BMI) (p < 0.05). Observed clinical impression of mood (CIM), was not impacted by PEG usage (p > 0.05). Overall results support PEG as a palliative intervention for ALS patients with ≥50 FVC %predict at PEG insertion. Full article
(This article belongs to the Special Issue Collection on Clinical Neuroscience)
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Prediction of PD-L1 Expression in Neuroblastoma via Computational Modeling
Brain Sci. 2019, 9(9), 221; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9090221 - 31 Aug 2019
Cited by 16
Abstract
Immunotherapy is a promising new therapeutic approach for neuroblastoma (NBM): an anti-GD2 vaccine combined with orally administered soluble beta-glucan is undergoing a phase II clinical trial and nivolumab and ipilimumab are being tested in recurrent and refractory tumors. Unfortunately, predictive biomarkers of response [...] Read more.
Immunotherapy is a promising new therapeutic approach for neuroblastoma (NBM): an anti-GD2 vaccine combined with orally administered soluble beta-glucan is undergoing a phase II clinical trial and nivolumab and ipilimumab are being tested in recurrent and refractory tumors. Unfortunately, predictive biomarkers of response to immunotherapy are currently not available for NBM patients. The aim of this study was to create a computational network model simulating the different intracellular pathways involved in NBM, in order to predict how the tumor phenotype may be influenced to increase the sensitivity to anti-programmed cell death-ligand-1 (PD-L1)/programmed cell death-1 (PD-1) immunotherapy. The model runs on COPASI software. In order to determine the influence of intracellular signaling pathways on the expression of PD-L1 in NBM, we first developed an integrated network of protein kinase cascades. Michaelis–Menten kinetics were associated to each reaction in order to tailor the different enzymes kinetics, creating a system of ordinary differential equations (ODEs). The data of this study offers a first tool to be considered in the therapeutic management of the NBM patient undergoing immunotherapeutic treatment. Full article
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Article
Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine
Brain Sci. 2019, 9(7), 172; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9070172 - 19 Jul 2019
Cited by 21
Abstract
Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave [...] Read more.
Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave of neuronal and glial depolarization originating in the occipital cortex, followed by temporary neuronal silencing. During a migraine attack, increased expression of inflammatory mediators, along with a decrease in the expression of anti-inflammatory genes, have been observed. The aim of this study was to evaluate the expression of inflammatory genes, in particular that of IL-1 receptor antagonist (IL-1RN), following CSD in a mouse model of familial hemiplegic migraine type 1 (FHM-1). We show here that the expression of IL-1RN was upregulated after the CSD, suggesting a possible attempt to modulate the inflammatory response. This study allows researchers to better understand the development of the disease and aids in the search for new therapeutic strategies in migraine. Full article
(This article belongs to the Special Issue Neuromodulation for Intractable Pain)
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Article
Emotional and Phenomenological Properties of Odor-Evoked Autobiographical Memories in Alzheimer’s Disease
Brain Sci. 2019, 9(6), 135; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9060135 - 10 Jun 2019
Cited by 15
Abstract
Autobiographical memory, which contains all personal memories relative to our identity, has been found to be impaired in Alzheimer’ Disease (AD). Recent research has demonstrated that odor may serve as a powerful cue for the recovery of autobiographical memories in AD. Building on [...] Read more.
Autobiographical memory, which contains all personal memories relative to our identity, has been found to be impaired in Alzheimer’ Disease (AD). Recent research has demonstrated that odor may serve as a powerful cue for the recovery of autobiographical memories in AD. Building on this research, we investigated emotional characteristics (arousal and valence) and subjective reliving of odor-evoked autobiographical memories in AD. We also investigated the relationship between these characteristics and depression. To this end, we invited participants with mild AD and controls to retrieve autobiographical memories after odor exposure or without odor. Results showed higher arousal, subjective reliving and more positive memories after odor exposure compared with the odor-free condition, these differences being observed only in AD participants. We also found that emotion (arousal and valence) and subjective reliving triggered by odor were associated with depressive symptoms in AD. These findings demonstrate that odor may be a useful cue to trigger more detailed, vivid and positive events in AD. Full article
(This article belongs to the Special Issue Olfaction as a Marker for Psychiatric and Neurological Diseases)
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Article
Joint Modulation of Facial Expression Processing by Contextual Congruency and Task Demands
Brain Sci. 2019, 9(5), 116; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9050116 - 17 May 2019
Cited by 14
Abstract
Faces showing expressions of happiness or anger were presented together with sentences that described happiness-inducing or anger-inducing situations. Two main variables were manipulated: (i) congruency between contexts and expressions (congruent/incongruent) and (ii) the task assigned to the participant, discriminating the emotion shown by [...] Read more.
Faces showing expressions of happiness or anger were presented together with sentences that described happiness-inducing or anger-inducing situations. Two main variables were manipulated: (i) congruency between contexts and expressions (congruent/incongruent) and (ii) the task assigned to the participant, discriminating the emotion shown by the target face (emotion task) or judging whether the expression shown by the face was congruent or not with the context (congruency task). Behavioral and electrophysiological results (event-related potentials (ERP)) showed that processing facial expressions was jointly influenced by congruency and task demands. ERP results revealed task effects at frontal sites, with larger positive amplitudes between 250–450 ms in the congruency task, reflecting the higher cognitive effort required by this task. Effects of congruency appeared at latencies and locations corresponding to the early posterior negativity (EPN) and late positive potential (LPP) components that have previously been found to be sensitive to emotion and affective congruency. The magnitude and spatial distribution of the congruency effects varied depending on the task and the target expression. These results are discussed in terms of the modulatory role of context on facial expression processing and the different mechanisms underlying the processing of expressions of positive and negative emotions. Full article
(This article belongs to the Special Issue Perceptual and Affective Mechanisms in Facial Expression Recognition)
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Article
Electrode Placement in Transcranial Direct Current Stimulation—How Reliable Is the Determination of C3/C4?
Brain Sci. 2019, 9(3), 69; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9030069 - 22 Mar 2019
Cited by 7
Abstract
The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. [...] Read more.
The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. M1 is identified by C3 and C4 of the 10/20 EEG system yet the reliability of 10/20 EEG measurements by novice research raters is unknown. We investigated the reliability of the 10/20 EEG measurements for C3 and C4 in 25 adult participants. Two novice raters were assessed for inter-rater reliability. Both raters received two hours of instruction from a registered neurodiagnostic technician. One of the raters completed the measurements across two testing days for intra-rater reliability. Relative reliability was determined using the intraclass coefficient (ICC) and absolute reliability. We observed a low to fair inter and intra-rater ICC for motor cortex measurements. The absolute reliability was <1.0 cm by different novice raters and on different days. Although a low error was observed, consideration of the integrity of the targeted region of the brain is critical when designing tDCS interventions in clinical populations who may have compromised brain structure, due to a lesion or altered anatomy. Full article
(This article belongs to the Special Issue Collection on Clinical Neuroscience)
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Article
Empagliflozin Ameliorates Type 2 Diabetes-Induced Ultrastructural Remodeling of the Neurovascular Unit and Neuroglia in the Female db/db Mouse
Brain Sci. 2019, 9(3), 57; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9030057 - 07 Mar 2019
Cited by 16
Abstract
Type 2 diabetes is associated with diabetic cognopathy. Anti-hyperglycemic sodium glucose transporter 2 (SGLT2) inhibitors have shown promise in reducing cognitive impairment in mice with type 2 diabetes mellitus. We recently described marked ultrastructural (US) remodeling of the neurovascular unit (NVU) in type [...] Read more.
Type 2 diabetes is associated with diabetic cognopathy. Anti-hyperglycemic sodium glucose transporter 2 (SGLT2) inhibitors have shown promise in reducing cognitive impairment in mice with type 2 diabetes mellitus. We recently described marked ultrastructural (US) remodeling of the neurovascular unit (NVU) in type 2 diabetic db/db female mice. Herein, we tested whether the SGLT-2 inhibitor, empagliflozin (EMPA), protects the NVU from abnormal remodeling in cortical gray and subcortical white matter. Ten-week-old female wild-type and db/db mice were divided into lean controls (CKC, n = 3), untreated db/db (DBC, n = 3), and EMPA-treated db/db (DBE, n = 3). Empagliflozin was added to mouse chow to deliver 10 mg kg−1 day−1 and fed for ten weeks, initiated at 10 weeks of age. Brains from 20-week-old mice were immediately immersion fixed for transmission electron microscopic study. Compared to CKC, DBC exhibited US abnormalities characterized by mural endothelial cell tight and adherens junction attenuation and/or loss, pericyte attenuation and/or loss, basement membrane thickening, glia astrocyte activation with detachment and retraction from mural cells, microglia cell activation with aberrant mitochondria, and oligodendrocyte–myelin splitting, disarray, and axonal collapse. We conclude that these abnormalities in the NVU were prevented in DBE. Empagliflozin may provide neuroprotection in the diabetic brain. Full article
(This article belongs to the Section Neuroglia)
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Article
Active Navigation in Virtual Environments Benefits Spatial Memory in Older Adults
Brain Sci. 2019, 9(3), 47; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9030047 - 26 Feb 2019
Cited by 16
Abstract
We investigated age differences in memory for spatial routes that were either actively or passively encoded. A series of virtual environments were created and presented to 20 younger (Mean age = 19.71) and 20 older (Mean age = 74.55) adults, through a cardboard [...] Read more.
We investigated age differences in memory for spatial routes that were either actively or passively encoded. A series of virtual environments were created and presented to 20 younger (Mean age = 19.71) and 20 older (Mean age = 74.55) adults, through a cardboard viewer. During encoding, participants explored routes presented within city, park, and mall virtual environments, and were later asked to re-trace their travelled routes. Critically, participants encoded half the virtual environments by passively viewing a guided tour along a pre-selected route, and half through active exploration with volitional control of their movements by using a button press on the viewer. During retrieval, participants were placed in the same starting location and asked to retrace the previously traveled route. We calculated the percentage overlap in the paths travelled at encoding and retrieval, as an indicator of spatial memory accuracy, and examined various measures indexing individual differences in their cognitive approach and visuo-spatial processing abilities. Results showed that active navigation, compared to passive viewing during encoding, resulted in a higher accuracy in spatial memory, with the magnitude of this memory enhancement being significantly larger in older than in younger adults. Regression analyses showed that age and score on the Hooper Visual Organizational test predicted spatial memory accuracy, following the passive and active encoding of routes. The model predicting accuracy following active encoding additionally included the distance of stops from an intersection as a significant predictor, illuminating a cognitive approach that specifically contributes to memory benefits in following active navigation. Results suggest that age-related deficits in spatial memory can be reduced by active encoding. Full article
(This article belongs to the Special Issue Cognitive Aging)
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Article
Working Memory, Cognitive Load and Cardiorespiratory Fitness: Testing the CRUNCH Model with Near-Infrared Spectroscopy
Brain Sci. 2019, 9(2), 38; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9020038 - 09 Feb 2019
Cited by 12
Abstract
The present study aimed to examine the effects of chronological age and cardiorespiratory fitness (CRF) on cognitive performance and prefrontal cortex activity, and to test the compensation-related utilization of neural circuits hypothesis (CRUNCH). A total of 19 young adults (18–22 years) and 37 [...] Read more.
The present study aimed to examine the effects of chronological age and cardiorespiratory fitness (CRF) on cognitive performance and prefrontal cortex activity, and to test the compensation-related utilization of neural circuits hypothesis (CRUNCH). A total of 19 young adults (18–22 years) and 37 older ones (60–77 years) with a high or low CRF level were recruited to perform a working memory updating task under three different cognitive load conditions. Prefrontal cortex hemodynamic responses were continuously recorded using functional near-infrared spectroscopy, and behavioral performances and perceived difficulty were measured. Results showed that chronological age had deleterious effects on both cognitive performance and prefrontal cortex activation under a higher cognitive load. In older adults, however, higher levels of CRF were related to increased bilateral prefrontal cortex activation patterns that allowed them to sustain better cognitive performances, especially under the highest cognitive load. These results are discussed in the light of the neurocognitive CRUNCH model. Full article
(This article belongs to the Special Issue Exercising against Age-Effects on the Brain)
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Article
Assessment and Management of HIV-Associated Cognitive Impairment: Experience from a Multidisciplinary Memory Service for People Living with HIV
Brain Sci. 2019, 9(2), 37; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9020037 - 08 Feb 2019
Cited by 11
Abstract
As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present [...] Read more.
As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients seen by the clinic. We present patient demographic data, assessment outcomes, diagnoses given and interventions delivered to those seen in the clinic. 41 patients (79%) of those seen in the clinic had objective CI: 16 (31%) met criteria for HIV-associated Neurocognitive Disorder (HAND), 2 (4%) were diagnosed with dementia, 14 (27%) showed CI associated with mental illness and/or drugs/alcohol, 7 (13%) had CI which was attributed to factors other than HIV and in 2 (4%) patients the cause remains unclear. 32 (62%) patients showed some abnormality on Magnetic Resonance Imaging (MRI) brain scans. Patients attending the clinic performed significantly worse than normative scores on all tests of global cognition and executive function. Interventions offered to patients included combination antiretroviral therapy modification, signposting to other services, case management, further health investigations and in-clinic advice. Our experience suggests that the need exists for specialist HIV memory services and that such a model of working can be successfully implemented into HIV patient care. Further work is needed on referral criteria and pathways. Diagnostic processes and treatment offered needs to consider and address the multifactorial aetiology of CI in HIV and this is essential for effective assessment and management. Full article
(This article belongs to the Special Issue Update on HIV-Associated Neurocognitive Disorders (HAND))
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Article
Neurostimulation for Intractable Chronic Pain
Brain Sci. 2019, 9(2), 23; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci9020023 - 24 Jan 2019
Cited by 20
Abstract
The field of neuromodulation has seen unprecedented growth over the course of the last decade with novel waveforms, hardware advancements, and novel chronic pain indications. We present here an updated review on spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. [...] Read more.
The field of neuromodulation has seen unprecedented growth over the course of the last decade with novel waveforms, hardware advancements, and novel chronic pain indications. We present here an updated review on spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. We focus on mechanisms of action, clinical indications, and future areas of research. We also present current drawbacks with current stimulation technology and suggest areas of future advancements. Given the current shortage of viable treatment options using a pharmacological based approach and conservative interventional therapies, neuromodulation presents an interesting area of growth and development for the interventional pain field and provides current and future practitioners a fresh outlook with regards to its place in the chronic pain treatment paradigm. Full article
(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

Review

Review
COVID-19 and Alzheimer’s Disease
Brain Sci. 2021, 11(3), 305; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci11030305 - 27 Feb 2021
Cited by 11
Abstract
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, [...] Read more.
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, and renal manifestations. Several mechanisms have been proposed to explain the potential SARS-CoV-2 neurological injury that could lead to the development of neurodegenerative diseases, including Alzheimer’s Disease (AD). A mutualistic relationship between AD and COVID-19 seems to exist. On the one hand, COVID-19 patients seem to be more prone to developing AD. On the other hand, AD patients could be more susceptible to severe COVID-19. In this review, we sought to provide an overview on the relationship between AD and COVID-19, focusing on the potential role of biomarkers, which could represent precious tool for early identification of COVID-19 patients at high risk of developing AD. Full article
(This article belongs to the Special Issue Biochemical Biomarkers and Neurodegenerative Diseases)
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Review
Trends in Autism Research in the Field of Education in Web of Science: A Bibliometric Study
Brain Sci. 2020, 10(12), 1018; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10121018 - 21 Dec 2020
Cited by 8
Abstract
Autism spectrum disorder (ASD) is conceived as a neurodevelopmental disorder. The scientific literature welcomes studies that reflect the possible singularities that people with ASD may present both in their daily lives and at an educational level. The main objective of this study is [...] Read more.
Autism spectrum disorder (ASD) is conceived as a neurodevelopmental disorder. The scientific literature welcomes studies that reflect the possible singularities that people with ASD may present both in their daily lives and at an educational level. The main objective of this study is to analyze the scientific production on the term autism in Web of Science, focused on the educational field, in order to identify the research trends in this field of study. The intention is to offer researchers who study autism in the educational field some clear research directions. A bibliometric-type methodology was developed using the scientific mapping technique. For this purpose, a performance analysis and a co-word analysis were carried out. Work was conducted with an analysis unit of 5512 documents. The results show that the volume of production has been irregular from the beginning to the present. The collection of documents on the subject began to be relevant, in terms of the volume of production, from 2007, and this has persisted to the present. It is concluded that there are two lines of research. The first is the line focused on mothers of children with ASD and the second is the line of research focused on young people with ASD. In addition, since 2012, new lines of research have been generated, focused on the diagnosis and inclusion of these students in educational centers. Full article
(This article belongs to the Section Developmental Neuroscience)
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Review
The Sleeping Brain: Harnessing the Power of the Glymphatic System through Lifestyle Choices
Brain Sci. 2020, 10(11), 868; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10110868 - 17 Nov 2020
Cited by 12
Abstract
The glymphatic system is a “pseudo-lymphatic” perivascular network distributed throughout the brain, responsible for replenishing as well as cleansing the brain. Glymphatic clearance is the macroscopic process of convective fluid transport in which harmful interstitial metabolic waste products are removed from the brain [...] Read more.
The glymphatic system is a “pseudo-lymphatic” perivascular network distributed throughout the brain, responsible for replenishing as well as cleansing the brain. Glymphatic clearance is the macroscopic process of convective fluid transport in which harmful interstitial metabolic waste products are removed from the brain intima. This paper addresses the glymphatic system, its dysfunction and the major consequences of impaired clearance in order to link neurodegeneration and glymphatic activity with lifestyle choices. Glymphatic clearance can be manipulated by sleep deprivation, cisterna magna puncture, acetazolamide or genetic deletion of AQP4 channels, but how lifestyle choices affect this brain-wide clearance system remains to be resolved. This paper will synthesize existing literature on glymphatic clearance, sleep, Alzheimer’s disease and lifestyle choices, in order to harness the power of this mass transport system, promote healthy brain ageing and possibly prevent neurodegenerative processes. This paper concludes that 1. glymphatic clearance plays a major role in Alzheimer’s pathology; 2. the vast majority of waste clearance occurs during sleep; 3. dementias are associated with sleep disruption, alongside an age-related decline in AQP4 polarization; and 4. lifestyle choices such as sleep position, alcohol intake, exercise, omega-3 consumption, intermittent fasting and chronic stress all modulate glymphatic clearance. Lifestyle choices could therefore alter Alzheimer’s disease risk through improved glymphatic clearance, and could be used as a preventative lifestyle intervention for both healthy brain ageing and Alzheimer’s disease. Full article
(This article belongs to the Special Issue Effects of Sleep Disruption on Daytime Functioning)
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Review
Emerging Neurological and Psychobiological Aspects of COVID-19 Infection
Brain Sci. 2020, 10(11), 852; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10110852 - 12 Nov 2020
Cited by 11
Abstract
The SARS-CoV-2 virus, first reported in December 2019 in China, is the causative agent of the current COVID-19 pandemic that, at the time of writing (1 November 2020) has infected almost 43 million people and caused the death of more than 1 million [...] Read more.
The SARS-CoV-2 virus, first reported in December 2019 in China, is the causative agent of the current COVID-19 pandemic that, at the time of writing (1 November 2020) has infected almost 43 million people and caused the death of more than 1 million people. The spectrum of clinical manifestations observed during COVID-19 infection varies from asymptomatic to critical life-threatening clinical conditions. Emerging evidence shows that COVID-19 affects far more organs than just the respiratory system, including the heart, kidneys, blood vessels, liver, as well as the central nervous system (CNS) and the peripheral nervous system (PNS). It is also becoming clear that the neurological and psychological disturbances that occur during the acute phase of the infection may persist well beyond the recovery. The aim of this review is to propel further this emerging and relevant field of research related to the pathophysiology of neurological manifestation of COVID-19 infection (Neuro-COVID). We will summarize the PNS and CNS symptoms experienced by people with COVID-19 both during infection and in the recovery phase. Diagnostic and pharmacological findings in this field of study are strongly warranted to address the neurological and psychological symptoms of COVID-19. Full article
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Review
Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia
Brain Sci. 2020, 10(10), 742; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10100742 - 16 Oct 2020
Cited by 10
Abstract
The biochemical integrity of the brain is paramount to the function of the central nervous system, and oxidative stress is a key contributor to cerebral biochemical impairment. Oxidative stress, which occurs when an imbalance arises between the production of reactive oxygen species (ROS) [...] Read more.
The biochemical integrity of the brain is paramount to the function of the central nervous system, and oxidative stress is a key contributor to cerebral biochemical impairment. Oxidative stress, which occurs when an imbalance arises between the production of reactive oxygen species (ROS) and the efficacy of the antioxidant defense mechanism, is believed to play a role in the pathophysiology of various brain disorders. One such disorder, schizophrenia, not only causes lifelong disability but also induces severe emotional distress; however, because of its onset in early adolescence or adulthood and its progressive development, consuming natural antioxidant products may help regulate the pathogenesis of schizophrenia. Therefore, elucidating the functions of ROS and dietary antioxidants in the pathogenesis of schizophrenia could help formulate improved therapeutic strategies for its prevention and treatment. This review focuses specifically on the roles of ROS and oxidative damage in the pathophysiology of schizophrenia, as well as the effects of nutrition, antipsychotic use, cognitive therapies, and quality of life on patients with schizophrenia. By improving our understanding of the effects of various nutrients on schizophrenia, it may become possible to develop nutritional strategies and supplements to treat the disorder, alleviate its symptoms, and facilitate long-term recovery. Full article
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Review
The Involvement of Hypothalamus–Pituitary–Adrenal (HPA) Axis in Suicide Risk
Brain Sci. 2020, 10(9), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10090653 - 21 Sep 2020
Cited by 10
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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Review
Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms
Brain Sci. 2020, 10(9), 639; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10090639 - 16 Sep 2020
Cited by 13
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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Review
Cannabinoids for People with ASD: A Systematic Review of Published and Ongoing Studies
Brain Sci. 2020, 10(9), 572; https://0-doi-org.brum.beds.ac.uk/10.3390/brainsci10090572 - 20 Aug 2020
Cited by 13
Abstract
The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Additionally, cannabidiol (CBD), the [...] Read more.
The etiopathogenesis of autism spectrum disorder (ASD) remains largely unclear. Among other biological hypotheses, researchers have evidenced an imbalance in the endocannabinoid (eCB) system, which regulates some functions typically impaired in ASD, such as emotional responses and social interaction. Additionally, cannabidiol (CBD), the non-intoxicating component of Cannabis sativa, was recently approved for treatment-resistant epilepsy. Epilepsy represents a common medical condition in people with ASD. Additionally, the two conditions share some neuropathological mechanisms, particularly GABAergic dysfunctions. Hence, it was hypothesized that cannabinoids could be useful in improving ASD symptoms. Our systematic review was conducted according to the PRISMA guidelines and aimed to summarize the literature regarding the use of cannabinoids in ASD. After searching in Web of KnowledgeTM, PsycINFO, and Embase, we included ten studies (eight papers and two abstracts). Four ongoing trials were retrieved in ClinicalTrials.gov. The findings were promising, as cannabinoids appeared to improve some ASD-associated symptoms, such as problem behaviors, sleep problems, and hyperactivity, with limited cardiac and metabolic side effects. Conversely, the knowledge of their effects on ASD core symptoms is scarce. Interestingly, cannabinoids generally allowed to reduce the number of prescribed medications and decreased the frequency of seizures in patients with comorbid epilepsy. Mechanisms of action could be linked to the excitatory/inhibitory imbalance found in people with ASD. However, further trials with better characterization and homogenization of samples, and well-defined outcomes should be implemented. Full article
(This article belongs to the Special Issue Advances in Autism Research)
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