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Brain Sci., Volume 10, Issue 10 (October 2020) – 101 articles

Cover Story (view full-size image): Children with fragile X syndrome (FXS) exhibit deficits in a variety of cognitive processes within the executive function domain. As working memory (WM) is known to support a wide range of cognitive, learning and adaptive functions, WM computer-based training programs have the potential to benefit people with FXS and other forms of intellectual and developmental disability (IDD). However, research on the effectiveness of WM training has been mixed. The current study is a follow-up “deep dive” into the data collected during a randomized controlled trial of Cogmed (Stockholm, Sweden) WM training in children with FXS. View this paper
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15 pages, 700 KiB  
Article
A Disruption in the Balance of Attentional Systems Plays a Role in Trait Anxiety
by Mark R. Minnick, Koraly E. Pérez-Edgar and José A. Soto
Brain Sci. 2020, 10(10), 761; https://doi.org/10.3390/brainsci10100761 - 21 Oct 2020
Cited by 5 | Viewed by 2141
Abstract
Elevated levels of anxiety are associated with attentional threat biases and inefficient attentional control, with the latter requiring sustained cognitive effort. The current study assessed self-reported and behavioral evidence of attentional functioning, along with electrodermal activity (EDA; measured via changes in skin conductance [...] Read more.
Elevated levels of anxiety are associated with attentional threat biases and inefficient attentional control, with the latter requiring sustained cognitive effort. The current study assessed self-reported and behavioral evidence of attentional functioning, along with electrodermal activity (EDA; measured via changes in skin conductance level [SCL reactivity]) as an index of sympathetic arousal, to examine whether these vulnerabilities are evident among individuals with elevated trait anxiety (non-clinical). Fifty-nine participants completed a working memory span task measuring attentional control under high cognitive load. A visual change detection task assessed stimulus-driven attention as an indicator of vigilance to non-threatening visual information. Trait anxiety was self-reported. SCL was captured at rest and during the working memory task. Results revealed that trait anxiety was positively related to speed of visual change detection, without accuracy costs, suggesting enhanced vigilance for neutral visual information among those higher in trait anxiety. Trait anxiety also moderated the relation between change detection speed and attentional control, such that attentional vigilance was not associated with variation in attentional control for individuals higher in trait anxiety. However, for individuals lower in trait anxiety, vigilance was negatively associated with attention control. The relationship between vigilance and attentional control was also moderated by SCL reactivity such that the association was only significant at lower SCL reactivity levels. Taken together, results suggest that individuals higher in trait anxiety demonstrate greater attentional control in the service of visual detection, but greater attentional control may come at the cost of increased sympathetic arousal. Full article
(This article belongs to the Special Issue Relationship between Executive Functions, Anxiety Disorders and Other Related Disorders)
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19 pages, 4744 KiB  
Article
Glycyrrhizin Blocks the Detrimental Effects of HMGB1 on Cortical Neurogenesis after Traumatic Neuronal Injury
by Susruta Manivannan, Balkis Harari, Maryam Muzaffar, Omar Elalfy, Sameera Hettipathirannahelage, Zoe James, Feras Sharouf, Chloe Ormonde, Mouhamed Alsaqati, William Gray and Malik Zaben
Brain Sci. 2020, 10(10), 760; https://doi.org/10.3390/brainsci10100760 - 21 Oct 2020
Cited by 6 | Viewed by 2786
Abstract
Despite medical advances, neurological recovery after severe traumatic brain injury (TBI) remains poor. Elevated levels of high mobility group box protein-1 (HMGB1) are associated with poor outcomes; likely via interaction with receptors for advanced-glycation-end-products (RAGE). We examined the hypothesis that HMGB1 post-TBI is [...] Read more.
Despite medical advances, neurological recovery after severe traumatic brain injury (TBI) remains poor. Elevated levels of high mobility group box protein-1 (HMGB1) are associated with poor outcomes; likely via interaction with receptors for advanced-glycation-end-products (RAGE). We examined the hypothesis that HMGB1 post-TBI is anti-neurogenic and whether this is pharmacologically reversible. Post-natal rat cortical mixed neuro-glial cell cultures were subjected to needle-scratch injury and examined for HMGB1-activation/neuroinflammation. HMGB1-related genes/networks were examined using genome-wide RNA-seq studies in cortical perilesional tissue samples from adult mice. Post-natal rat cortical neural stem/progenitor cell cultures were generated to quantify effects of injury-condition medium (ICM) on neurogenesis with/without RAGE antagonist glycyrrhizin. Needle-injury upregulated TNF-α/NOS-2 mRNA-expressions at 6 h, increased proportions of activated microglia, and caused neuronal loss at 24 h. Transcriptome analysis revealed activation of HMGB1 pathway genes/canonical pathways in vivo at 24 h. A 50% increase in HMGB1 protein expression, and nuclear-to-cytoplasmic translocation of HMGB1 in neurons and microglia at 24 h post-injury was demonstrated in vitro. ICM reduced total numbers/proportions of neuronal cells, but reversed by 0.5 μM glycyrrhizin. HMGB1 is activated following in vivo post mechanical injury, and glycyrrhizin alleviates detrimental effects of ICM on cortical neurogenesis. Our findings highlight glycyrrhizin as a potential therapeutic agent post-TBI. Full article
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15 pages, 526 KiB  
Article
Chronic Valproic Acid Administration Increases Plasma, Liver, and Brain Ammonia Concentration and Suppresses Glutamine Synthetase Activity
by Abdelnaser A. Badawy, Rasha Elghaba, Mohamed Soliman, Abdelaziz M. Hussein, Sana A. AlSadrah, Amira Awadalla and Osama A. Abulseoud
Brain Sci. 2020, 10(10), 759; https://doi.org/10.3390/brainsci10100759 - 21 Oct 2020
Cited by 4 | Viewed by 2806
Abstract
Asymptomatic valproic acid (VPA)-induced hyperammonemia in the absence of liver impairment is fairly common. However, the underlying mechanisms through which VPA causes elevation in plasma ammonia (NH4) remains under investigation. Male Sprague Dawley rats (n = 72) were randomly allocated [...] Read more.
Asymptomatic valproic acid (VPA)-induced hyperammonemia in the absence of liver impairment is fairly common. However, the underlying mechanisms through which VPA causes elevation in plasma ammonia (NH4) remains under investigation. Male Sprague Dawley rats (n = 72) were randomly allocated to receive VPA 400 mg/kg, 200 mg/kg, or vehicle IP daily for either 8, 14, or 28 consecutive days. The behavioral effects of VPA were assessed. Plasma, liver, and prefrontal cortex (PFC), striatum (Str), and cerebellum (Cere) were collected 1 h post last injection and assayed for NH4 concentration and glutamine synthetase (GS) enzyme activity. Chronic VPA treatment caused attenuation of measured behavioral reflexes (p < 0.0001) and increase in plasma NH4 concentration (p < 0.0001). The liver and brain also showed significant increase in tissue NH4 concentrations (p < 0.0001 each) associated with significant reduction in GS activity (p < 0.0001 and p = 0.0003, respectively). Higher tissue NH4 concentrations correlated with reduced GS activity in the liver (r = −0.447, p = 0.0007) but not in the brain (r = −0.058, p = 0.4). Within the brain, even though NH4 concentrations increased in the PFC (p = 0.001), Str (p < 0.0001), and Cere (p = 0.01), GS activity was reduced only in the PFC (p < 0.001) and not in Str (p = 0.2) or Cere (p = 0.1). These results suggest that VPA-induced elevation in plasma NH4 concentration could be related, at least in part, to the suppression of GS activity in liver and brain tissues. However, even though GS is the primary mechanism in brain NH4 clearance, the suppression of brain GS does not seem to be the main factor in explaining the elevation in brain NH4 concentration. Further research is urgently needed to investigate brain NH4 dynamics under chronic VPA treatment and whether VPA clinical efficacy in treating seizure disorders and bipolar mania is impacted by its effect on GS activity or other NH4 metabolizing enzymes. Full article
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13 pages, 645 KiB  
Review
Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab
by Despoina Florou, Maria Katsara, Jack Feehan, Efthimios Dardiotis and Vasso Apostolopoulos
Brain Sci. 2020, 10(10), 758; https://doi.org/10.3390/brainsci10100758 - 20 Oct 2020
Cited by 49 | Viewed by 12602
Abstract
Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via [...] Read more.
Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis Research—Series II)
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14 pages, 2209 KiB  
Article
Functional MRI Reveals Locomotion-Control Neural Circuits in Human Brainstem
by Pengxu Wei, Tong Zou, Zeping Lv and Yubo Fan
Brain Sci. 2020, 10(10), 757; https://doi.org/10.3390/brainsci10100757 - 20 Oct 2020
Cited by 9 | Viewed by 2750
Abstract
The cuneiform nucleus (CN) and the pedunculopontine nucleus (PPN) in the midbrain control coordinated locomotion in vertebrates, but whether similar mechanisms exist in humans remain to be elucidated. Using functional magnetic resonance imaging, we found that simulated gait evoked activations in the CN, [...] Read more.
The cuneiform nucleus (CN) and the pedunculopontine nucleus (PPN) in the midbrain control coordinated locomotion in vertebrates, but whether similar mechanisms exist in humans remain to be elucidated. Using functional magnetic resonance imaging, we found that simulated gait evoked activations in the CN, PPN, and other brainstem regions in humans. Brain networks were constructed for each condition using functional connectivity. Bilateral CN–PPN and the four pons–medulla regions constituted two separate modules under all motor conditions, presenting two brainstem functional units for locomotion control. Outside- and inside-brainstem nodes were connected more densely although the links between the two groups were sparse. Functional connectivity and network analysis revealed the role of brainstem circuits in dual-task walking and walking automaticity. Together, our findings indicate that the CN, PPN, and other brainstem regions participate in locomotion control in humans. Full article
(This article belongs to the Special Issue Functional Brain Imaging of Locomotion in Aging and Age-Related Diseases)
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17 pages, 1582 KiB  
Review
Perspectives on Human Hearing Loss, Cochlear Regeneration, and the Potential for Hearing Restoration Therapies
by Patricia M. White
Brain Sci. 2020, 10(10), 756; https://doi.org/10.3390/brainsci10100756 - 20 Oct 2020
Cited by 8 | Viewed by 3584
Abstract
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells [...] Read more.
Most adults who acquire hearing loss find it to be a disability that is poorly corrected by current prosthetics. This gap drives current research in cochlear mechanosensory hair cell regeneration and in hearing restoration. Birds and fish can spontaneously regenerate lost hair cells through a process that has become better defined in the last few years. Findings from these studies have informed new research on hair cell regeneration in the mammalian cochlea. Hair cell regeneration is one part of the greater problem of hearing restoration, as hearing loss can stem from a myriad of causes. This review discusses these issues and recent findings, and places them in the greater social context of need and community. Full article
(This article belongs to the Special Issue Inner Ear Therapy)
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11 pages, 1841 KiB  
Article
The Relationship between Carotid Doppler Ultrasound and EEG Metrics in Healthy Preschoolers and Adults
by Galina V. Portnova, Aleksandra V. Maslennikova and Elena V. Proskurnina
Brain Sci. 2020, 10(10), 755; https://doi.org/10.3390/brainsci10100755 - 20 Oct 2020
Viewed by 1902
Abstract
Despite widespread using electroencephalography (EEG) and Doppler ultrasound in pediatric neurology clinical practice, there are still no well-known correlations between these methods that could contribute to a better understanding of brain processes and development of neurological pathology. This study aims to reveal relationship [...] Read more.
Despite widespread using electroencephalography (EEG) and Doppler ultrasound in pediatric neurology clinical practice, there are still no well-known correlations between these methods that could contribute to a better understanding of brain processes and development of neurological pathology. This study aims to reveal relationship between EEG and Doppler ultrasound methods. We compared two cohorts of adults and preschool children with no history of neurological or mental diseases. The data analysis included investigation of EEG and carotid blood flow indexes, which are significant in neurological diagnosis, as well as calculation of linear and non-linear EEG parameters and ratios between the systolic peak velocities of carotid arteries and carotid blood asymmetry. We have found age-dependent correlations between EEG and power Doppler ultrasound imaging (PDUI) data. Carotid blood flow asymmetry correlated with delta-rhythm power spectral density only in preschoolers. The ratios of blood flow velocities in the internal carotid arteries to those in the common carotid arteries correlated with higher peak alpha frequency and lower fractal dimension; moreover, they were associated with lower Epworth sleepiness scale scores. The study revealed significant correlations between EEG and PDUI imaging indexes, which are different for healthy children and adults. Despite the fact that the correlations were associated with non-clinical states such as overwork or stress, we assumed that the investigated parameters could be applicable for clinical trials. Full article
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22 pages, 2857 KiB  
Article
A Three-Stage Teacher, Student Neural Networks and Sequential Feed Forward Selection-Based Feature Selection Approach for the Classification of Autism Spectrum Disorder
by Naseer Ahmed Khan, Samer Abdulateef Waheeb, Atif Riaz and Xuequn Shang
Brain Sci. 2020, 10(10), 754; https://doi.org/10.3390/brainsci10100754 - 19 Oct 2020
Cited by 13 | Viewed by 2995
Abstract
Autism disorder, generally known as Autism Spectrum Disorder (ASD) is a brain disorder characterized by lack of communication skills, social aloofness and repetitions in the actions in the patients, which is affecting millions of the people across the globe. Accurate identification of autistic [...] Read more.
Autism disorder, generally known as Autism Spectrum Disorder (ASD) is a brain disorder characterized by lack of communication skills, social aloofness and repetitions in the actions in the patients, which is affecting millions of the people across the globe. Accurate identification of autistic patients is considered a challenging task in the domain of brain disorder science. To address this problem, we have proposed a three-stage feature selection approach for the classification of ASD on the preprocessed Autism Brain Imaging Data Exchange (ABIDE) rs-fMRI Dataset. In the first stage, a large neural network which we call a “Teacher ” was trained on the correlation-based connectivity matrix to learn the latent representation of the input. In the second stage an autoencoder which we call a “Student” autoencoder was given the task to learn those trained “Teacher” embeddings using the connectivity matrix input. Lastly, an SFFS-based algorithm was employed to select the subset of most discriminating features between the autistic and healthy controls. On the combined site data across 17 sites, we achieved the maximum 10-fold accuracy of 82% and for the individual site-wise data, based on 5-fold accuracy, our results outperformed other state of the art methods in 13 out of the total 17 site-wise comparisons. Full article
(This article belongs to the Special Issue Neural Networks and Connectivity among Brain Regions)
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8 pages, 384 KiB  
Brief Report
Understanding Novel Metaphors: A Milestone in the Developmental Trajectory of Children with Agenesis of the Corpus Callosum?
by Sergio Melogno, Maria Antonietta Pinto, Chiara Pollice, Fausto Badolato, Guido Trasimeni and Pasquale Parisi
Brain Sci. 2020, 10(10), 753; https://doi.org/10.3390/brainsci10100753 - 19 Oct 2020
Cited by 1 | Viewed by 2133
Abstract
This study explores novel metaphor comprehension in a 7.2-year-old child (conventionally called RJ) with complete and isolated agenesis of the corpus callosum (ACC). RJ’s cognitive level was adequate for his age as well as most of his linguistic competencies. The child’s performance was [...] Read more.
This study explores novel metaphor comprehension in a 7.2-year-old child (conventionally called RJ) with complete and isolated agenesis of the corpus callosum (ACC). RJ’s cognitive level was adequate for his age as well as most of his linguistic competencies. The child’s performance was compared to typically developing (TD) controls on a test assessing novel metaphor comprehension for preschoolers. RJ’s performance showed a delay of about three years in relation to the expected level for his age, and also a significant gap compared to the TDs. The results highlighted the possibility to detect weaknesses in understanding novel metaphors in children with ACC, in spite of their apparently adequate linguistic capabilities. An early detection of a weakness in this area can pave the way to neurolinguistic treatment in order to enhance the understanding of nonliteral meaning, which, in the developmental trajectory, will be increasingly involved in everyday life communication. Future research should explore more in-depth a capability that intrinsically requires high interconnectivity, such as novel metaphor comprehension, in a brain in development where the major tract connecting the two hemispheres is missing. Full article
(This article belongs to the Section Developmental Neuroscience)
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16 pages, 4023 KiB  
Article
Early Onset Epilepsy Caused by Low-Grade Epilepsy-Associated Tumors and Focal Meningeal Involvement
by Luca De Palma, Chiara Pepi, Alessandro De Benedictis, Nicola Pietrafusa, Angela Mastronuzzi, Antonella Cacchione, Giusy Carfì-Pavia, Camilla Rossi-Espagnet, Francesca Diomedi-Camassei, Sabrina Rossi, Antonio Napolitano, Andrea Carai, Giovanna Stefania Colafati, Daniela Longo, Paolo Curatolo, Federico Vigevano, Carlo Efisio Marras and Nicola Specchio
Brain Sci. 2020, 10(10), 752; https://doi.org/10.3390/brainsci10100752 - 18 Oct 2020
Cited by 1 | Viewed by 2422
Abstract
Background: Low-grade epilepsy-associated neuroepithelial tumors (LEATs) are a frequent etiology in pediatric patients with epilepsy undergoing surgery. Objective: To identify differences in clinical and post-surgical follow-up between patients with focal meningeal involvement (MI) and those without MI within our cohort of [...] Read more.
Background: Low-grade epilepsy-associated neuroepithelial tumors (LEATs) are a frequent etiology in pediatric patients with epilepsy undergoing surgery. Objective: To identify differences in clinical and post-surgical follow-up between patients with focal meningeal involvement (MI) and those without MI within our cohort of pediatric patients with LEATs. Methods: We retrospectively reviewed all pediatric patients (<18 y) who underwent epilepsy surgery between 2011 and 2017 at our hospital. Cohort inclusion required histological diagnosis of LEATs and post-surgical follow-up of ≥2 y. We subsequently stratified patients according to presence of neuroradiological MI. Results: We identified 37 patients: five with MI and 32 without. Half of patients (19) were drug sensitive at surgery; similar between groups. The group with MI differed mainly for age of epilepsy-onset (0.6 vs. 7.0 y) but not for epilepsy duration (0.9 vs. 1.5 y). Post-surgery radiological follow-up (median 4.0 y; IQR 2.8–5.0 y) did not indicate disease progression. Seizure outcome was excellent in both groups, with 34 patients overall being both drug- and seizure-free. Conclusions: Our study identified a new subgroup of LEATs with focal MI and excellent post-surgical outcome. Moreover, this highlights the effectiveness of early surgery in pediatric LEATs. Full article
(This article belongs to the Special Issue Advances in Epilepsy)
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27 pages, 1194 KiB  
Review
The Influence of Recreational Substance Use in TMS Research
by Claudia V. Turco, Sarah O. Arsalan and Aimee J. Nelson
Brain Sci. 2020, 10(10), 751; https://doi.org/10.3390/brainsci10100751 - 18 Oct 2020
Cited by 10 | Viewed by 4152
Abstract
(1) Background: Transcranial magnetic stimulation (TMS) approaches are widely used to study cortical and corticospinal function. However, responses to TMS are subject to significant intra-and inter-individual variability. Acute and chronic exposure to recreational substances alters the excitability of the sensorimotor system and may [...] Read more.
(1) Background: Transcranial magnetic stimulation (TMS) approaches are widely used to study cortical and corticospinal function. However, responses to TMS are subject to significant intra-and inter-individual variability. Acute and chronic exposure to recreational substances alters the excitability of the sensorimotor system and may contribute to the variability in TMS outcome measures. The increasing prevalence of recreational substance use poses a significant challenge for executing TMS studies, but there is a lack of clarity regarding the influence of these substances on sensorimotor function. (2) Methods: The literature investigating the influence of alcohol, nicotine, caffeine and cannabis on TMS outcome measures of corticospinal, intracortical and interhemispheric excitability was reviewed. (3) Results: Both acute and chronic use of recreational substances modulates TMS measures of excitability. Despite the abundance of research in this field, we identify knowledge gaps that should be addressed in future studies to better understand the influence of these substances on TMS outcomes. (4) Conclusions: This review highlights the need for TMS studies to take into consideration the history of participant substance use and to control for acute substance use prior to testing. Full article
(This article belongs to the Special Issue A Decade of Brain Sciences)
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12 pages, 447 KiB  
Article
Suicidal Ideation and Suicidal Attempts in Referred Adolescents with High Functioning Autism Spectrum Disorder and Comorbid Bipolar Disorder: A Pilot Study
by Gabriele Masi, Silvia Scullin, Antonio Narzisi, Pietro Muratori, Marinella Paciello, Deborah Fabiani, Francesca Lenzi, Maria Mucci and Giulia D’Acunto
Brain Sci. 2020, 10(10), 750; https://doi.org/10.3390/brainsci10100750 - 17 Oct 2020
Cited by 14 | Viewed by 3861
Abstract
Suicidal ideation and attempts in adolescents are closely associated to bipolar disorders (BD). Growing evidence also suggests that high functioning autism spectrum disorders (HF-ASD) are at increased risk for suicidal ideation and behaviors. Although BD and HF-ASD are frequently comorbid, no studies explored [...] Read more.
Suicidal ideation and attempts in adolescents are closely associated to bipolar disorders (BD). Growing evidence also suggests that high functioning autism spectrum disorders (HF-ASD) are at increased risk for suicidal ideation and behaviors. Although BD and HF-ASD are frequently comorbid, no studies explored suicidality in these individuals. This exploratory study addressed this issue in a clinical group of inpatient adolescents referred to a psychiatric emergency unit. Seventeen adolescents with BD and HF-ASD and severe suicidal ideation or attempts (BD-ASD-S), were compared to 17 adolescents with BD and HF-ASD without suicidal ideation or attempts (BD-ASD-noS), and to 18 adolescents with BD and suicidal ideation or attempts without ASD (BD-noASD-S), using a structured assessment methodology. Individuals with BD-ASD-S had a higher intelligence quotient, more severe clinical impairment, more lethality in suicide attempts, more internalizing symptoms, less impulsiveness, and lower social competence. Severity of ASD traits in individuals and parents did not correlate with suicidal risk. Some dimensions of resilience were protective in terms of repulsion by life and attraction to death. Main limitations are the small sample size, the lack of a control group of typically developing adolescents. However, a better understanding of the specificities of bipolar HF-ASD individuals with suicidality may improve prevention and treatment strategies. Full article
(This article belongs to the Special Issue Advances in Autism Research)
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14 pages, 1161 KiB  
Article
Effects of Combining High-Definition Transcranial Direct Current Stimulation with Short-Foot Exercise on Chronic Ankle Instability: A Pilot Randomized and Double-Blinded Study
by Yuanbo Ma, Keyi Yin, Wei Zhuang, Cui Zhang, Yong Jiang, Jin Huang, Brad Manor, Junhong Zhou and Yu Liu
Brain Sci. 2020, 10(10), 749; https://doi.org/10.3390/brainsci10100749 - 17 Oct 2020
Cited by 15 | Viewed by 3561
Abstract
(1) Background: Balance decline is highly prevalent in people suffering from chronic ankle instability (CAI). The control of balance depends upon multiple neurophysiologic systems including the activation of cortical brain regions (e.g., the primary sensorimotor cortex). The excitability of this region, however, is [...] Read more.
(1) Background: Balance decline is highly prevalent in people suffering from chronic ankle instability (CAI). The control of balance depends upon multiple neurophysiologic systems including the activation of cortical brain regions (e.g., the primary sensorimotor cortex). The excitability of this region, however, is diminished in people with CAI. In this pilot double-blinded randomized controlled trial, we tested the effects of high-definition transcranial direct current stimulation (HD-tDCS) designed to facilitate the excitability of M1 and S1 in combination with short-foot exercise (SFE) training on proprioception and dynamic balance performance in individuals with CAI. (2) Methods: Thirty young adults completed baseline assessments including the Active Movement Extent Discrimination Apparatus (AMEDA), Joint Position Reproduction (JPR) test, Y-balance test, and the Sensory Organization Test (SOT). They were then randomized to receive a four-week intervention of SFE in combination with tDCS (i.e., HD-tDCS+SFE) or sham (i.e., control) stimulation. Baseline assessments were repeated once-weekly throughout the intervention and during a two-week follow-up period. (3) Results: Twenty-eight participants completed this study. Blinding procedures were successful and no adverse events were reported. As compared to the control group, the HD-tDCS+SFE group exhibited significant improvements in the JPR test, the Y balance test, and the SOT at different time points. No group by time interaction was observed in AMEDA test performance. (4) Conclusions: HD-tDCS combined with SFE may improve dynamic balance and proprioception in CAI. Larger, more definitive trials with extended follow-up are warranted. Full article
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14 pages, 1259 KiB  
Article
Auditory and Somatosensory P3 Are Complementary for the Assessment of Patients with Disorders of Consciousness
by Jitka Annen, Isabella Mertel, Ren Xu, Camille Chatelle, Damien Lesenfants, Rupert Ortner, Estelle A.C. Bonin, Christoph Guger, Steven Laureys and Friedemann Müller
Brain Sci. 2020, 10(10), 748; https://doi.org/10.3390/brainsci10100748 - 17 Oct 2020
Cited by 13 | Viewed by 2828
Abstract
The evaluation of the level of consciousness in patients with disorders of consciousness (DOC) is primarily based on behavioural assessments. Patients with unresponsive wakefulness syndrome (UWS) do not show any sign of awareness of their environment, while minimally conscious state (MCS) patients show [...] Read more.
The evaluation of the level of consciousness in patients with disorders of consciousness (DOC) is primarily based on behavioural assessments. Patients with unresponsive wakefulness syndrome (UWS) do not show any sign of awareness of their environment, while minimally conscious state (MCS) patients show reproducible but fluctuating signs of awareness. Some patients, although with remaining cognitive abilities, are not able to exhibit overt voluntary responses at the bedside and may be misdiagnosed as UWS. Several studies investigated functional neuroimaging and neurophysiology as an additional tool to evaluate the level of consciousness and to detect covert command following in DOC. Most of these studies are based on auditory stimulation, neglecting patients suffering from decreased or absent hearing abilities. In the present study, we aim to assess the response to a P3-based paradigm in 40 patients with DOC and 12 healthy participants using auditory (AEP) and vibrotactile (VTP) stimulation. To this end, an EEG-based brain-computer interface was used at DOC patient’s bedside. We compared the significance of the P3 performance (i.e., the interpretation of significance of the evoked P3 response) as obtained by ‘direct processing’ (i.e., theoretical-based significance threshold) and ‘offline processing’ (i.e., permutation-based single subject level threshold). We evaluated whether the P3 performances were dependent on clinical variables such as diagnosis (UWS and MCS), aetiology and time since injury. Last we tested the dependency of AEP and VTP performances at the single subject level. Direct processing tends to overestimate P3 performance. We did not find any difference in the presence of a P3 performance according to the level of consciousness (UWS vs. MCS) or the aetiology (traumatic vs. non-traumatic brain injury). The performance achieved at the AEP paradigm was independent from what was achieved at the VTP paradigm, indicating that some patients performed better on the AEP task while others performed better on the VTP task. Our results support the importance of using multimodal approaches in the assessment of DOC patients in order to optimise the evaluation of patient’s abilities. Full article
(This article belongs to the Special Issue Recent Advances in the Study of Altered State of Consciousness)
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16 pages, 2648 KiB  
Article
Comprehensive Analysis of RNA-Seq Gene Expression Profiling of Brain Transcriptomes Reveals Novel Genes, Regulators, and Pathways in Autism Spectrum Disorder
by Md Rezanur Rahman, Maria Cristina Petralia, Rosella Ciurleo, Alessia Bramanti, Paolo Fagone, Md Shahjaman, Lang Wu, Yanfa Sun, Beste Turanli, Kazim Yalcin Arga, Md Rafiqul Islam, Tania Islam and Ferdinando Nicoletti
Brain Sci. 2020, 10(10), 747; https://doi.org/10.3390/brainsci10100747 - 17 Oct 2020
Cited by 36 | Viewed by 7062
Abstract
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with deficits in social communication ability and repetitive behavior. The pathophysiological events involved in the brain of this complex disease are still unclear. Methods: In this study, we aimed to profile the gene expression [...] Read more.
Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with deficits in social communication ability and repetitive behavior. The pathophysiological events involved in the brain of this complex disease are still unclear. Methods: In this study, we aimed to profile the gene expression signatures of brain cortex of ASD patients, by using two publicly available RNA-seq studies, in order to discover new ASD-related genes. Results: We detected 1567 differentially expressed genes (DEGs) by meta-analysis, where 1194 were upregulated and 373 were downregulated genes. Several ASD-related genes previously reported were also identified. Our meta-analysis identified 235 new DEGs that were not detected using the individual RNA-seq studies used. Some of those genes, including seven DEGs (PAK1, DNAH17, DOCK8, DAPP1, PCDHAC2, and ERBIN, SLC7A7), have been confirmed in previous reports to be associated with ASD. Gene Ontology (GO) and pathways analysis showed several molecular pathways enriched by the DEGs, namely, osteoclast differentiation, TNF signaling pathway, complement and coagulation cascade. Topological analysis of protein–protein interaction of the ASD brain cortex revealed proteomics hub gene signatures: MYC, TP53, HDAC1, CDK2, BAG3, CDKN1A, GABARAPL1, EZH2, VIM, and TRAF1. We also identified the transcriptional factors (TFs) regulating DEGs, namely, FOXC1, GATA2, YY1, FOXL1, USF2, NFIC, NFKB1, E2F1, TFAP2A, HINFP. Conclusion: Novel core genes and molecular signatures involved with ASD were identified by our meta-analysis. Full article
(This article belongs to the Special Issue Advances in Autism Research: Series II)
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20 pages, 858 KiB  
Article
Towards New Diagnostic Approaches in Disorders of Consciousness: A Proof of Concept Study on the Promising Use of Imagery Visuomotor Task
by Antonino Naro and Rocco Salvatore Calabrò
Brain Sci. 2020, 10(10), 746; https://doi.org/10.3390/brainsci10100746 - 17 Oct 2020
Cited by 6 | Viewed by 2318
Abstract
Background: advanced paraclinical approaches using functional neuroimaging and electroencephalography (EEG) allow identifying patients who are covertly aware despite being diagnosed as unresponsive wakefulness syndrome (UWS). Bedside detection of covert awareness employing motor imagery tasks (MI), which is a universally accepted clinical indicator of [...] Read more.
Background: advanced paraclinical approaches using functional neuroimaging and electroencephalography (EEG) allow identifying patients who are covertly aware despite being diagnosed as unresponsive wakefulness syndrome (UWS). Bedside detection of covert awareness employing motor imagery tasks (MI), which is a universally accepted clinical indicator of awareness in the absence of overt behavior, may miss some of these patients, as they could still have a certain level of awareness. We aimed at assessing covert awareness in patients with UWS using a visuomotor-guided motor imagery task (VMI) during EEG recording. Methods: nine patients in a minimally conscious state (MCS), 11 patients in a UWS, and 15 healthy individuals (control group—CG) were provided with an VMI (imagine dancing while watching a group dance video to command), a simple-MI (imagine squeezing their right hand to command), and an advanced-MI (imagine dancing without watching a group dance video to command) to detect command-following. We analyzed the command-specific EEG responses (event-related synchronization/desynchronization—ERS/ERD) of each patient, assessing whether these responses were appropriate, consistent, and statistically similar to those elicited in the CG, as reliable markers of motor imagery. Results: All patients in MCS, all healthy individuals and one patient in UWS repeatedly and reliably generated appropriate EEG responses to distinct commands of motor imagery with a classification accuracy of 60–80%. Conclusions: VMI outperformed significantly MI tasks. Therefore, patients in UWS may be still misdiagnosed despite a rigorous clinical assessment and an appropriate MI assessment. It is thus possible to suggest that motor imagery tasks should be delivered to patients with chronic disorders of consciousness in visuomotor-aided modality (also in the rehabilitation setting) to greatly entrain patient’s participation. In this regard, the EEG approach we described has the clear advantage of being cheap, portable, widely available, and objective. It may be thus considered as, at least, a screening tool to identify the patients who deserve further, advanced paraclinical approaches. Full article
(This article belongs to the Special Issue Advances in Disorders of Consciousness)
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12 pages, 243 KiB  
Review
The Missing Pieces of the Puzzle: A Review on the Interactive Nature of A-Priori Expectancies and Attention Bias toward Threat
by Elinor Abado, Tatjana Aue and Hadas Okon-Singer
Brain Sci. 2020, 10(10), 745; https://doi.org/10.3390/brainsci10100745 - 17 Oct 2020
Cited by 8 | Viewed by 2821
Abstract
The role of attention bias in the etiology and maintenance of anxiety disorders has been studied extensively over decades. Attention bias reflects maladaptation in cognitive processing, as perceived threatening stimuli receive prioritized processing even when they are task-irrelevant or factually unthreatening. Recently, there [...] Read more.
The role of attention bias in the etiology and maintenance of anxiety disorders has been studied extensively over decades. Attention bias reflects maladaptation in cognitive processing, as perceived threatening stimuli receive prioritized processing even when they are task-irrelevant or factually unthreatening. Recently, there has been some interest in the role of a-priori expectancies in attention bias toward threat. The current review article will present recent studies as examples that emphasize the need for more comprehensive research about the interactive effects of various factors that affect the relationship between expectancies and attention bias toward threatening stimuli in anxiety. The current review article suggests a holistic view, which advocates for more integrative research, as a dynamic network could underlie changes in attention bias. The study of the interaction between such factors, with a focus on expectancy, can lead to more ecological and clinically important results, and thus to more informed and fine-tuned treatments that are based on manipulation of expectancies. Such methods, in turn, can also help in shedding light on the research of attention bias, in a mutual relationship between research and therapy. Full article
15 pages, 1504 KiB  
Article
Combined Supra- and Sub-Lesional Epidural Electrical Stimulation for Restoration of the Motor Functions after Spinal Cord Injury in Mini Pigs
by Filip Fadeev, Anton Eremeev, Farid Bashirov, Roman Shevchenko, Andrei Izmailov, Vage Markosyan, Mikhail Sokolov, Julia Kalistratova, Anastasiia Khalitova, Ravil Garifulin, Rustem Islamov and Igor Lavrov
Brain Sci. 2020, 10(10), 744; https://doi.org/10.3390/brainsci10100744 - 16 Oct 2020
Cited by 12 | Viewed by 3251
Abstract
This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8–9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced [...] Read more.
This study evaluates the effect of combined epidural electrical stimulation (EES) applied above (C5) and below (L2) the spinal cord injury (SCI) at T8–9 combined with motor training on the restoration of sensorimotor function in mini pigs. The motor evoked potentials (MEP) induced by EES applied at C5 and L2 levels were recorded in soleus muscles before and two weeks after SCI. EES treatment started two weeks after SCI and continued for 6 weeks led to improvement in multiple metrics, including behavioral, electrophysiological, and joint kinematics outcomes. In control animals after SCI a multiphasic M-response was observed during M/H-response testing, while animals received EES-enable training demonstrated the restoration of the M-response and H-reflex, although at a lower amplitude. The joint kinematic and assessment with Porcine Thoracic Injury Behavior scale (PTIBS) motor recovery scale demonstrated improvement in animals that received EES-enable training compared to animals with no treatment. The positive effect of two-level (cervical and lumbar) epidural electrical stimulation on functional restoration in mini pigs following spinal cord contusion injury in mini pigs could be related with facilitation of spinal circuitry at both levels and activation of multisegmental coordination. This approach can be taken as a basis for the future development of neuromodulation and neurorehabilitation therapy for patients with spinal cord injury. Full article
(This article belongs to the Special Issue Mechanisms of Neuromodulation and Rehabilitation after Spinal Cord Injury)
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16 pages, 1972 KiB  
Article
Genome, Environment, Microbiome and Metabolome in Autism (GEMMA) Study Design: Biomarkers Identification for Precision Treatment and Primary Prevention of Autism Spectrum Disorders by an Integrated Multi-Omics Systems Biology Approach
by Jacopo Troisi, Reija Autio, Thanos Beopoulos, Carmela Bravaccio, Federica Carraturo, Giulio Corrivetti, Stephen Cunningham, Samantha Devane, Daniele Fallin, Serguei Fetissov, Manuel Gea, Antonio Giorgi, François Iris, Lokesh Joshi, Sarah Kadzielski, Aletta Kraneveld, Himanshu Kumar, Christine Ladd-Acosta, Geraldine Leader, Arlene Mannion, Elise Maximin, Alessandra Mezzelani, Luciano Milanesi, Laurent Naudon, Lucia N. Peralta Marzal, Paula Perez Pardo, Naika Z. Prince, Sylvie Rabot, Guus Roeselers, Christophe Roos, Lea Roussin, Giovanni Scala, Francesco Paolo Tuccinardi and Alessio Fasanoadd Show full author list remove Hide full author list
Brain Sci. 2020, 10(10), 743; https://doi.org/10.3390/brainsci10100743 - 16 Oct 2020
Cited by 17 | Viewed by 7702
Abstract
Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service [...] Read more.
Autism Spectrum Disorder (ASD) affects approximately 1 child in 54, with a 35-fold increase since 1960. Selected studies suggest that part of the recent increase in prevalence is likely attributable to an improved awareness and recognition, and changes in clinical practice or service availability. However, this is not sufficient to explain this epidemiological phenomenon. Research points to a possible link between ASD and intestinal microbiota because many children with ASD display gastro-intestinal problems. Current large-scale datasets of ASD are limited in their ability to provide mechanistic insight into ASD because they are predominantly cross-sectional studies that do not allow evaluation of perspective associations between early life microbiota composition/function and later ASD diagnoses. Here we describe GEMMA (Genome, Environment, Microbiome and Metabolome in Autism), a prospective study supported by the European Commission, that follows at-risk infants from birth to identify potential biomarker predictors of ASD development followed by validation on large multi-omics datasets. The project includes clinical (observational and interventional trials) and pre-clinical studies in humanized murine models (fecal transfer from ASD probands) and in vitro colon models. This will support the progress of a microbiome-wide association study (of human participants) to identify prognostic microbiome signatures and metabolic pathways underlying mechanisms for ASD progression and severity and potential treatment response. Full article
(This article belongs to the Special Issue Advances in Autism Research)
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24 pages, 1221 KiB  
Review
Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia
by Samskruthi Madireddy and Sahithi Madireddy
Brain Sci. 2020, 10(10), 742; https://doi.org/10.3390/brainsci10100742 - 16 Oct 2020
Cited by 29 | Viewed by 4147
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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15 pages, 747 KiB  
Article
Brain Magnetic Resonance Findings in 117 Children with Autism Spectrum Disorder under 5 Years Old
by Magali Jane Rochat, Giacomo Distefano, Monica Maffei, Francesco Toni, Annio Posar, Maria Cristina Scaduto, Federica Resca, Cinzia Cameli, Elena Bacchelli, Elena Maestrini and Paola Visconti
Brain Sci. 2020, 10(10), 741; https://doi.org/10.3390/brainsci10100741 - 16 Oct 2020
Cited by 8 | Viewed by 5437
Abstract
We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans [...] Read more.
We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these results we discuss the role that brain MRI may play in the diagnostic procedure of ASD. Full article
(This article belongs to the Special Issue Recent Advances in Neurodevelopmental Disorders)
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14 pages, 2551 KiB  
Article
Noisy Galvanic Vestibular Stimulation (Stochastic Resonance) Changes Electroencephalography Activities and Postural Control in Patients with Bilateral Vestibular Hypofunction
by Li-Wei Ko, Rupesh Kumar Chikara, Po-Yin Chen, Ying-Chun Jheng, Chien-Chih Wang, Yi-Chiang Yang, Lieber Po-Hung Li, Kwong-Kum Liao, Li-Wei Chou and Chung-Lan Kao
Brain Sci. 2020, 10(10), 740; https://doi.org/10.3390/brainsci10100740 - 15 Oct 2020
Cited by 19 | Viewed by 3883
Abstract
Patients with bilateral vestibular hypofunction (BVH) often suffer from imbalance, gait problems, and oscillopsia. Noisy galvanic vestibular stimulation (GVS), a technique that non-invasively stimulates the vestibular afferents, has been shown to enhance postural and walking stability. However, no study has investigated how it [...] Read more.
Patients with bilateral vestibular hypofunction (BVH) often suffer from imbalance, gait problems, and oscillopsia. Noisy galvanic vestibular stimulation (GVS), a technique that non-invasively stimulates the vestibular afferents, has been shown to enhance postural and walking stability. However, no study has investigated how it affects stability and neural activities while standing and walking with a 2 Hz head yaw turning. Herein, we investigated this issue by comparing differences in neural activities during standing and walking with a 2 Hz head turning, before and after noisy GVS. We applied zero-mean gaussian white noise signal stimulations in the mastoid processes of 10 healthy individuals and seven patients with BVH, and simultaneously recorded electroencephalography (EEG) signals with 32 channels. We analyzed the root mean square (RMS) of the center of pressure (COP) sway during 30 s of standing, utilizing AMTI force plates (Advanced Mechanical Technology Inc., Watertown, MA, USA). Head rotation quality when walking with a 2 Hz head yaw, with and without GVS, was analyzed using a VICON system (Vicon Motion Systems Ltd., Oxford, UK) to evaluate GVS effects on static and dynamic postural control. The RMS of COP sway was significantly reduced during GVS while standing, for both patients and healthy subjects. During walking, 2 Hz head yaw movements was significantly improved by noisy GVS in both groups. Accordingly, the EEG power of theta, alpha, beta, and gamma bands significantly increased in the left parietal lobe after noisy GVS during walking and standing in both groups. GVS post-stimulation effect changed EEG activities in the left and right precentral gyrus, and the right parietal lobe. After stimulation, EEG activity changes were greater in healthy subjects than in patients. Our findings reveal noisy GVS as a non-invasive therapeutic alternative to improve postural stability in patients with BVH. This novel approach provides insight to clinicians and researchers on brain activities during noisy GVS in standing and walking conditions in both healthy and BVH patients. Full article
(This article belongs to the Special Issue Brain Stimulation and Neuroplasticity)
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7 pages, 566 KiB  
Communication
Anti-Gravity Treadmill Training for Freezing of Gait in Parkinson’s Disease
by José Fidel Baizabal-Carvallo, Marlene Alonso-Juarez and Robert Fekete
Brain Sci. 2020, 10(10), 739; https://doi.org/10.3390/brainsci10100739 - 15 Oct 2020
Cited by 5 | Viewed by 3466
Abstract
Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor impairment. Freezing of gait, impaired mobility and falls are common problems in these patients. We aimed to evaluate the effect of a novel therapy for these patients. Methods: We studied patients with [...] Read more.
Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor impairment. Freezing of gait, impaired mobility and falls are common problems in these patients. We aimed to evaluate the effect of a novel therapy for these patients. Methods: We studied patients with moderate to severe freezing of gait who underwent antigravity treadmill training twice a week for 4 consecutive weeks with 50% reduction of body weight. Results: We enrolled 26 consecutive patients with PD, 19 completed the study. There were 10 males; mean age at evaluation was 72.7 ± 10.1 years. Compared to baseline, patients showed improvement in the Freezing of Gait Questionnaire (p = 0.001); and a mean reduction of 7 s in the Timed Up & Go (TUG) test (p = 0.004). Moderate or significant improvement in gait was reported by 84% of patients. Conclusions: Antigravity treadmill training improved freezing of gait and mobility in patients with PD. Full article
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8 pages, 389 KiB  
Communication
Exercise Intensity May Not Moderate the Acute Effects of Functional Circuit Training on Cognitive Function: A Randomized Crossover Trial
by Jan Wilke and Caroline Royé
Brain Sci. 2020, 10(10), 738; https://doi.org/10.3390/brainsci10100738 - 14 Oct 2020
Cited by 2 | Viewed by 2472
Abstract
Functional circuit training (FCT) has been demonstrated to acutely enhance cognitive performance (CP). However, the moderators of this observation are unknown. This study aimed to elucidate the role of exercise intensity. According to an a priori sample size calculation, n = 24 healthy [...] Read more.
Functional circuit training (FCT) has been demonstrated to acutely enhance cognitive performance (CP). However, the moderators of this observation are unknown. This study aimed to elucidate the role of exercise intensity. According to an a priori sample size calculation, n = 24 healthy participants (26 ± 3 years, 13 females), in randomized order, performed a single 15-min bout of FCT with low (20–39% of the heart rate reserve/HRR), moderate (40–59% HRR) or high intensity (maximal effort). Immediately pre- and post-workout, CP was measured by use of the Digit Span test, Stroop test and Trail Making test. Non-parametric data analyses did not reveal significant differences between conditions (p > 0.05) although parameter-free 95% confidence intervals showed pre-post improvements in some outcomes at moderate and high intensity only. The effort level does not seem to be a major effect modifier regarding short-term increases in CP following HCT in young active adults. Full article
(This article belongs to the Special Issue Studying Brain Activity in Sports Performance)
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21 pages, 1563 KiB  
Article
On Nonlinear Regression for Trends in Split-Belt Treadmill Training
by Usman Rashid, Nitika Kumari, Nada Signal, Denise Taylor and Alain C. Vandal
Brain Sci. 2020, 10(10), 737; https://doi.org/10.3390/brainsci10100737 - 14 Oct 2020
Cited by 6 | Viewed by 2243
Abstract
Single and double exponential models fitted to step length symmetry series are used to evaluate the timecourse of adaptation and de-adaptation in instrumented split-belt treadmill tasks. Whilst the nonlinear regression literature has developed substantially over time, the split-belt treadmill training literature has not [...] Read more.
Single and double exponential models fitted to step length symmetry series are used to evaluate the timecourse of adaptation and de-adaptation in instrumented split-belt treadmill tasks. Whilst the nonlinear regression literature has developed substantially over time, the split-belt treadmill training literature has not been fully utilising the fruits of these developments. In this research area, the current methods of model fitting and evaluation have three significant limitations: (i) optimisation algorithms that are used for model fitting require a good initial guess for regression parameters; (ii) the coefficient of determination (R2) is used for comparing and evaluating models, yet it is considered to be an inadequate measure of fit for nonlinear regression; and, (iii) inference is based on comparison of the confidence intervals for the regression parameters that are obtained under the untested assumption that the nonlinear model has a good linear approximation. In this research, we propose a transformed set of parameters with a common language interpretation that is relevant to split-belt treadmill training for both the single and double exponential models. We propose parameter bounds for the exponential models which allow the use of particle swarm optimisation for model fitting without an initial guess for the regression parameters. For model evaluation and comparison, we propose the use of residual plots and Akaike’s information criterion (AIC). A method for obtaining confidence intervals that does not require the assumption of a good linear approximation is also suggested. A set of MATLAB (MathWorks, Inc., Natick, MA, USA) functions developed in order to apply these methods are also presented. Single and double exponential models are fitted to both the group-averaged and participant step length symmetry series in an experimental dataset generating new insights into split-belt treadmill training. The proposed methods may be useful for research involving analysis of gait symmetry with instrumented split-belt treadmills. Moreover, the demonstration of the suggested statistical methods on an experimental dataset may help the uptake of these methods by a wider community of researchers that are interested in timecourse of motor training. Full article
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4 pages, 194 KiB  
Editorial
What about “Pharming”? Issues Regarding the Misuse of Prescription and Over-the-Counter Drugs
by Stefania Chiappini and Fabrizio Schifano
Brain Sci. 2020, 10(10), 736; https://doi.org/10.3390/brainsci10100736 - 14 Oct 2020
Cited by 35 | Viewed by 4818
Abstract
Recently, a range of prescription and over-the-counter (OTC) drugs have emerged as being used recreationally, either on their own or in combination with other substances, both licit and illicit, including new psychoactive substances (NPS). Among them, the misuse of prescription drugs involves not [...] Read more.
Recently, a range of prescription and over-the-counter (OTC) drugs have emerged as being used recreationally, either on their own or in combination with other substances, both licit and illicit, including new psychoactive substances (NPS). Among them, the misuse of prescription drugs involves not only traditionally recorded substances, such as benzodiazepines and opioid pain relievers, but also gabapentinoids (e.g., pregabalin and gabapentin); some antidepressants, e.g., bupropion and venlafaxine; some second-generation antipsychotics, e.g., quetiapine and olanzapine. Moreover, the use of some OTC for recreational purposes appears on the increase, especially in vulnerable categories such as young people/youths, including the use of high dosages of the antidiarrheal loperamide; first-generation antihistamines, e.g., promethazine, cyclizine, and diphenhydramine; cough and cold preparations containing dextromethorphan and/or codeine. In this context, the role of the Internet has rapidly increased, playing a significant role both in the diffusion of emerging trends of drug misuse among users and experimenters, and the marketing, sale, and distribution of drugs through online pharmacies. This phenomenon within the context of a rapidly modifying drug scenario is a globally recognized health problem, determining severe adverse consequences, including fatalities, and represents a challenge for clinicians in general, psychiatrists, public health, and drug-control policies. Full article
15 pages, 2396 KiB  
Article
An Acute Application of Cerebellar Transcranial Direct Current Stimulation Does Not Improve Motor Performance in Parkinson’s Disease
by Lidio Lima de Albuquerque, Milan Pantovic, Mitchel Clingo, Katherine Fischer, Sharon Jalene, Merrill Landers, Zoltan Mari and Brach Poston
Brain Sci. 2020, 10(10), 735; https://doi.org/10.3390/brainsci10100735 - 14 Oct 2020
Cited by 11 | Viewed by 2289
Abstract
Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson’s disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of [...] Read more.
Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson’s disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on medications. The study was a randomized, double-blind, SHAM-controlled, between-subjects design. Twenty-two participants with PD were allocated to either a c-tDCS group or a SHAM group. All participants completed one experimental session and performed two motor tasks with their most affected hand in a Baseline condition (no stimulation) and an Experimental condition. The motor tasks were a visuomotor isometric precision grip task (PGT) and a rapid arm movement task (AMT). The primary dependent variables were force error and endpoint error in the PGT and AMT, respectively. There were no significant differences in force error or endpoint error in the Experimental condition between the c-tDCS and SHAM groups. These results indicate that an acute application of c-tDCS does not enhance motor performance in hand and arm tasks in PD. Longer-term c-tDCS application over multiple days may be needed to enhance motor function in PD. Full article
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13 pages, 1156 KiB  
Article
A Comparison of Classification Techniques to Predict Brain-Computer Interfaces Accuracy Using Classifier-Based Latency Estimation
by Md Rakibul Mowla, Jesus D. Gonzalez-Morales, Jacob Rico-Martinez, Daniel A. Ulichnie and David E. Thompson
Brain Sci. 2020, 10(10), 734; https://doi.org/10.3390/brainsci10100734 - 14 Oct 2020
Cited by 6 | Viewed by 2182
Abstract
P300-based Brain-Computer Interface (BCI) performance is vulnerable to latency jitter. To investigate the role of latency jitter on BCI system performance, we proposed the classifier-based latency estimation (CBLE) method. In our previous study, CBLE was based on least-squares (LS) and stepwise linear discriminant [...] Read more.
P300-based Brain-Computer Interface (BCI) performance is vulnerable to latency jitter. To investigate the role of latency jitter on BCI system performance, we proposed the classifier-based latency estimation (CBLE) method. In our previous study, CBLE was based on least-squares (LS) and stepwise linear discriminant analysis (SWLDA) classifiers. Here, we aim to extend the CBLE method using sparse autoencoders (SAE) to compare the SAE-based CBLE method with LS- and SWLDA-based CBLE. The newly-developed SAE-based CBLE and previously used methods are also applied to a newly-collected dataset to reduce the possibility of spurious correlations. Our results showed a significant (p<0.001) negative correlation between BCI accuracy and estimated latency jitter. Furthermore, we also examined the effect of the number of electrodes on each classification technique. Our results showed that on the whole, CBLE worked regardless of the classification method and electrode count; by contrast the effect of the number of electrodes on BCI performance was classifier dependent. Full article
(This article belongs to the Special Issue Collection on Neural Engineering)
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13 pages, 1302 KiB  
Brief Report
Antidepressant-Like Properties of Fish Oil on Postpartum Depression-Like Rats Model: Involvement of Serotonergic System
by Nurul Uyun Abdul Aziz, Samaila Musa Chiroma, Mohamad Aris Mohd Moklas, Mohd Ilham Adenan, Amin Ismail and Mohamad Taufik Hidayat Baharuldin
Brain Sci. 2020, 10(10), 733; https://doi.org/10.3390/brainsci10100733 - 13 Oct 2020
Cited by 8 | Viewed by 2920
Abstract
Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, [...] Read more.
Pathophysiology of postpartum depression (PPD) has been associated with many factors, such as neuroendocrine, neuroinflammation and neurotransmitter changes. Fish oil (FO) improves PPD both in humans and animals. However, little is known with regards to its pharmacology on a PPD-like rat model. Hence, the current study aimed at investigating the effects of FO on a PPD-like rat model. Female rats were induced with PPD-like symptoms and then randomly divided into six groups (n = 6) for two experimental protocols. Protocol 1 consisted of PPD-like rats (2 mL distilled water), PPD-like + FO (9 g/kg/d) and PPD-like + Fluoxetine (FLX) (15 mg/kg/d) groups of rats, whereas Protocol 2 consisted of PPD-like rats (2 mL distilled water) + PCPA (p-chlorophenylalanine) 150 mg/kg, PPD-like + FO (9 g/kg/d) + PCPA 150 mg/kg and PPD-like + FLX (15 mg/d) + PCPA 150 mg/kg groups of rats, respectively. All treatments were administered orally for 10 days postpartum, except PCPA, which was given intraperitoneally. Prior to euthanasia, the antidepressant-like effect of the FO was evaluated using the forced swimming test (FST) and open field test (OFT) on day 10 postpartum. Biochemical analysis of serotonin, serotonin metabolite and serotonin turnover from their prefrontal cortex and hippocampus were also measured. The results showed that FO decreased immobility time and increased swimming time significantly, but not climbing time in FST. Further, it also decreased serotonin metabolite and turnover significantly in the hippocampus of the PPD-like rats. In contrast, administration with PCPA reversed all the outcomes. The antidepressant-like effects of FO were found to be similar with that of FLX. Thus, it can be concluded that FO exerts its antidepressant-like effects in PPD-like rats through modulation of serotonergic system. Full article
(This article belongs to the Section Behavioral Neuroscience)
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11 pages, 223 KiB  
Review
Noise Induced Hearing Loss and Tinnitus—New Research Developments and Remaining Gaps in Disease Assessment, Treatment, and Prevention
by Tang-Chuan Wang, Ta-Yuan Chang, Richard Tyler, Ying-Ju Lin, Wen-Miin Liang, Yio-Wha Shau, Wei-Yong Lin, Yi-Wen Chen, Chia-Der Lin and Ming-Hsui Tsai
Brain Sci. 2020, 10(10), 732; https://doi.org/10.3390/brainsci10100732 - 13 Oct 2020
Cited by 21 | Viewed by 7205
Abstract
Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in [...] Read more.
Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential. Full article
(This article belongs to the Special Issue Central Auditory Plasticity)
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