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Brain Sci., Volume 8, Issue 8 (August 2018)

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Cover Story (view full-size image) SPAST HSP patient-derived olfactory neural stem cells have impaired transport of peroxisomes, a [...] Read more.
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Open AccessReview The Current State of Deep Brain Stimulation for Chronic Pain and Its Context in Other Forms of Neuromodulation
Brain Sci. 2018, 8(8), 158; https://doi.org/10.3390/brainsci8080158
Received: 17 July 2018 / Revised: 8 August 2018 / Accepted: 13 August 2018 / Published: 20 August 2018
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Abstract
Chronic intractable pain is debilitating for those touched, affecting 5% of the population. Deep brain stimulation (DBS) has fallen out of favour as the centrally implantable neurostimulation of choice for chronic pain since the 1970–1980s, with some neurosurgeons favouring motor cortex stimulation as
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Chronic intractable pain is debilitating for those touched, affecting 5% of the population. Deep brain stimulation (DBS) has fallen out of favour as the centrally implantable neurostimulation of choice for chronic pain since the 1970–1980s, with some neurosurgeons favouring motor cortex stimulation as the ‘last chance saloon’. This article reviews the available data and professional opinion of the current state of DBS as a treatment for chronic pain, placing it in the context of other neuromodulation therapies. We suggest DBS, with its newer target, namely anterior cingulate cortex (ACC), should not be blacklisted on the basis of a lack of good quality study data, which often fails to capture the merits of the treatment. Full article
(This article belongs to the Special Issue Neuromodulation for Intractable Pain)
Open AccessReview Magnetoencephalography: Clinical and Research Practices
Brain Sci. 2018, 8(8), 157; https://doi.org/10.3390/brainsci8080157
Received: 28 June 2018 / Revised: 7 August 2018 / Accepted: 11 August 2018 / Published: 17 August 2018
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Abstract
Magnetoencephalography (MEG) is a neurophysiological technique that detects the magnetic fields associated with brain activity. Synthetic aperture magnetometry (SAM), a MEG magnetic source imaging technique, can be used to construct both detailed maps of global brain activity as well as virtual electrode signals,
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Magnetoencephalography (MEG) is a neurophysiological technique that detects the magnetic fields associated with brain activity. Synthetic aperture magnetometry (SAM), a MEG magnetic source imaging technique, can be used to construct both detailed maps of global brain activity as well as virtual electrode signals, which provide information that is similar to invasive electrode recordings. This innovative approach has demonstrated utility in both clinical and research settings. For individuals with epilepsy, MEG provides valuable, nonredundant information. MEG accurately localizes the irritative zone associated with interictal spikes, often detecting epileptiform activity other methods cannot, and may give localizing information when other methods fail. These capabilities potentially greatly increase the population eligible for epilepsy surgery and improve planning for those undergoing surgery. MEG methods can be readily adapted to research settings, allowing noninvasive assessment of whole brain neurophysiological activity, with a theoretical spatial range down to submillimeter voxels, and in both humans and nonhuman primates. The combination of clinical and research activities with MEG offers a unique opportunity to advance translational research from bench to bedside and back. Full article
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Open AccessFeature PaperArticle Neural Responses to Consciously and Unconsciously Perceived Emotional Faces: A Spinal fMRI Study
Brain Sci. 2018, 8(8), 156; https://doi.org/10.3390/brainsci8080156
Received: 29 June 2018 / Revised: 8 August 2018 / Accepted: 14 August 2018 / Published: 17 August 2018
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Abstract
Emotional stimuli modulate activity in brain areas related to attention, perception, and movement. Similar increases in neural activity have been detected in the spinal cord, suggesting that this understudied component of the central nervous system is an important part of our emotional responses.
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Emotional stimuli modulate activity in brain areas related to attention, perception, and movement. Similar increases in neural activity have been detected in the spinal cord, suggesting that this understudied component of the central nervous system is an important part of our emotional responses. To date, previous studies of emotion-dependent spinal cord activity have utilized long presentations of complex emotional scenes. The current study differs from this research by (1) examining whether emotional faces will lead to enhanced spinal cord activity and (2) testing whether these stimuli require conscious perception to influence neural responses. Fifteen healthy undergraduate participants completed six spinal functional magnetic resonance imaging (fMRI) runs in which three one-minute blocks of fearful, angry, or neutral faces were interleaved with 40-s rest periods. In half of the runs, the faces were clearly visible while in the other half, the faces were displayed for only 17 ms. Spinal fMRI consisted of half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences targeting the cervical spinal cord. The results indicated that consciously perceived faces expressing anger elicited significantly more activity than fearful or neutral faces in ventral (motoric) regions of the cervical spinal cord. When stimuli were presented below the threshold of conscious awareness, neutral faces elicited significantly more activity than angry or fearful faces. Together, these data suggest that the emotional modulation of spinal cord activity is most impactful when the stimuli are consciously perceived and imply a potential threat toward the observer. Full article
(This article belongs to the Special Issue Functional Neuroimaging of the Spinal Cord)
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Open AccessReview Transcranial Direct Current Stimulation (tDCS) for Depression during Pregnancy: Scientific Evidence and What Is Being Said in the Media—A Systematic Review
Brain Sci. 2018, 8(8), 155; https://doi.org/10.3390/brainsci8080155
Received: 19 June 2018 / Revised: 8 August 2018 / Accepted: 11 August 2018 / Published: 14 August 2018
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Abstract
Major depression is the most frequent morbidity in pregnancy. The first-line therapies, psychopharmacologic treatment and psychotherapy, are either insufficient or may cause severe or teratogenic adverse events. As a result of its local limitation to the patient’s brain, transcranial direct current stimulation (tDCS)
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Major depression is the most frequent morbidity in pregnancy. The first-line therapies, psychopharmacologic treatment and psychotherapy, are either insufficient or may cause severe or teratogenic adverse events. As a result of its local limitation to the patient’s brain, transcranial direct current stimulation (tDCS) could potentially be an ideal treatment for pregnant women with depression. A literature search was conducted in medical databases, globally published newspapers, search engines, and clinical trial registers to collect all articles on tDCS for the treatment of depression during pregnancy. The aim of this review was to investigate the scientific evidence of tDCS use for depression during pregnancy and to compare these results with the textual and emotional perception in the media as interventions during pregnancy are under particular surveillance. We detected 13 medical articles dealing with tDCS for depression in pregnancy. Overall, the scientific evidence as well as articles in the media for tDCS in pregnancy are sparse, but promising. Further studies are required in this specifically vulnerable population of pregnant women to generate evidence. It is likely that public interest will increase when the results of a pilot study in Canada are published. Full article
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Open AccessReview Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders
Brain Sci. 2018, 8(8), 154; https://doi.org/10.3390/brainsci8080154
Received: 26 July 2018 / Revised: 8 August 2018 / Accepted: 10 August 2018 / Published: 13 August 2018
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Abstract
Males and females sometimes significantly differ in their propensity to develop neurological disorders. Females suffer more from mood disorders such as depression and anxiety, whereas males are more susceptible to deficits in the dopamine system including Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD)
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Males and females sometimes significantly differ in their propensity to develop neurological disorders. Females suffer more from mood disorders such as depression and anxiety, whereas males are more susceptible to deficits in the dopamine system including Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD) and autism. Despite this, biological sex is rarely considered when making treatment decisions in neurological disorders. A better understanding of the molecular mechanism(s) underlying sex differences in the healthy and diseased brain will help to devise diagnostic and therapeutic strategies optimal for each sex. Thus, the aim of this review is to discuss the available evidence on sex differences in neuropsychiatric and neurodegenerative disorders regarding prevalence, progression, symptoms and response to therapy. We also discuss the sex-related factors such as gonadal sex hormones and sex chromosome genes and how these might help to explain some of the clinically observed sex differences in these disorders. In particular, we highlight the emerging role of the Y-chromosome gene, SRY, in the male brain and its potential role as a male-specific risk factor for disorders such as PD, autism, and ADHD in many individuals. Full article
(This article belongs to the Special Issue Sex Differences in the Healthy and Diseased Brain)
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Open AccessReview JASPAC: Japan Spastic Paraplegia Research Consortium
Brain Sci. 2018, 8(8), 153; https://doi.org/10.3390/brainsci8080153
Received: 14 June 2018 / Revised: 6 August 2018 / Accepted: 10 August 2018 / Published: 13 August 2018
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Abstract
Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by weakness and spasticity of the lower extremities. HSPs are heterogeneous disorders that involve over 80 causative genes. The frequency of HSPs is estimated to be 10–100/1,000,000. With this background, the Japanese
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Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders characterized by weakness and spasticity of the lower extremities. HSPs are heterogeneous disorders that involve over 80 causative genes. The frequency of HSPs is estimated to be 10–100/1,000,000. With this background, the Japanese research group “Japan Spastic Paraplegia Research Consortium: JASPAC” was organized in 2006 to elucidate the molecular epidemiologies of HSPs in Japan and the molecular pathologies of HSPs. To date, the JASPAC has collected 714 HSP families and analyzed 488 index patients. We found 279 pathogenic variants or probable pathogenic variants of causative genes in the 488 HSP patients. According to our results, we found 178 families with autosomal dominant patients (65%), and 101 with autosomal recessive and sporadic patients (48%). We found 119 patients with SPG4, 17 with SPG3A, 15 with SPG31, 13 with SPG11, and 11 with SPG10. Other HSP genes were the cause in less than five patients. On the other hand, we could not find causative genes in 35% of the autosomal dominant patients, or 52% of the autosomal recessive and sporadic patients. We are now trying to find new causative genes and elucidate the molecular mechanisms underlying HSPs. Full article
(This article belongs to the Special Issue Advances in Genetics of Hereditary Spastic Paraplegia)
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Open AccessArticle Functional Near-Infrared Spectroscopy Recordings of Visuospatial Working Memory Processes. Part II: A Replication Study in Children on Sensitivity and Mental-Ability-Induced Differences in Functional Activation
Brain Sci. 2018, 8(8), 152; https://doi.org/10.3390/brainsci8080152
Received: 10 July 2018 / Revised: 7 August 2018 / Accepted: 9 August 2018 / Published: 12 August 2018
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Abstract
In a previous study in young adults, we showed that hemodynamic changes as measured by functional near-infrared spectroscopy (fNIRS) were sensitive for identifying visuospatial working memory (WM)-related functional brain activation in the prefrontal cortex. This functional activation, however, could not be verified for
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In a previous study in young adults, we showed that hemodynamic changes as measured by functional near-infrared spectroscopy (fNIRS) were sensitive for identifying visuospatial working memory (WM)-related functional brain activation in the prefrontal cortex. This functional activation, however, could not be verified for participants with far-above-average mental ability, suggesting different cognitive processes adopted by this group. The present study was designed to confirm these findings in 11- to 13-year-old children by applying the same study design, experimental task, fNIRS setup, and statistical approach. We successfully replicated the earlier findings on sensitivity of fNIRS with regard to visuospatial WM-specific task demands in our children sample. Likewise, mental-ability-induced differences in functional activation were even more pronounced in the children compared with in the young adults. By testing a children sample, we were able to not only replicate our previous findings based on adult participants but also generalize the validity of these findings to children. This latter aspect seems to be of particular significance considering the relatively large number of fNIRS studies on WM performance in children. Full article
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Open AccessArticle Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is not Enhanced after IGF Treatment
Brain Sci. 2018, 8(8), 151; https://doi.org/10.3390/brainsci8080151
Received: 18 June 2018 / Revised: 31 July 2018 / Accepted: 8 August 2018 / Published: 11 August 2018
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Abstract
Following traumatic brain injuries (TBI), insulin-like growth factor (IGF) is cortically widely upregulated. This upregulation has a potential role in the recovery of neuronal tissue, plasticity, and neurotrophic activity, though the molecular mechanisms involved in IGF regulation and the exact role of IGF
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Following traumatic brain injuries (TBI), insulin-like growth factor (IGF) is cortically widely upregulated. This upregulation has a potential role in the recovery of neuronal tissue, plasticity, and neurotrophic activity, though the molecular mechanisms involved in IGF regulation and the exact role of IGF after TBI remain unclear. Vitronectin (VN), an extracellular matrix (ECM) molecule, has recently been shown to be of importance for IGF-mediated cellular growth and migration. Since VN is downregulated after TBI, we hypothesized that insufficient VN levels after TBI impairs the potential beneficial activity of IGF. To test if vitronectin and IGF-1/IGFBP-2 could contribute to neurite growth, we cultured hippocampal neurons on ± vitronectin-coated coverslips and them treated with ± IGF-1/IGF binding protein 2 (IGFBP-2). Under same conditions, cell cultures were also subjected to in vitro trauma to investigate differences in the posttraumatic regenerative capacity with ± vitronectin-coated coverslips and with ± IGF-1/IGFBP-2 treatment. In both the control and trauma situations, hippocampal neurons showed a stronger growth pattern on vitronectin than on the control substrate. Surprisingly, the addition of IGF-1/IGFBP-2 showed a decrease in neurite growth. Since neurite growth was measured as the number of neurites per area, we hypothesized that IGF-1/IGFBP-2 contributes to the polarization of neurons and thus induced a less dense neurite network after IGF-1/IGFBP-2 treatment. This hypothesis could not be confirmed and we therefore conclude that vitronectin has a positive effect on neurite growth in vitro both under normal conditions and after trauma, but that addition of IGF-1/IGFBP-2 does not have a positive additive effect. Full article
(This article belongs to the Special Issue Novel Mechanisms and Strategies for Neural Repair)
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Open AccessReview Disentangling the Neural Basis of Cognitive Behavioral Therapy in Psychiatric Disorders: A Focus on Depression
Brain Sci. 2018, 8(8), 150; https://doi.org/10.3390/brainsci8080150
Received: 12 July 2018 / Revised: 7 August 2018 / Accepted: 8 August 2018 / Published: 9 August 2018
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Abstract
Background: Major depressive disorder (MDD) stands among the most frequent psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be effective for treating depression, yet its neural mechanisms of action are not well elucidated. The objective of this work is to assess
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Background: Major depressive disorder (MDD) stands among the most frequent psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be effective for treating depression, yet its neural mechanisms of action are not well elucidated. The objective of this work is to assess the available neuroimaging studies exploring CBT’s effects in adult patients with MDD. Methods: Computerized databases were consulted till April 2018 and a research was conducted according to PRISMA guidelines in order to identify original research articles published at any time in English and French languages on this topic. Results: Seventeen studies were identified. Only one study was randomized comparing CBT to pharmacological interventions, and none included an effective control. Following CBT, changes occurred in cerebral areas that are part of the fronto-limbic system, namely the cingulate cortex, prefrontal cortex and amygdala-hippocampal complex. However, the pattern of activation and connectivity in these areas varied across the studies. Conclusion: A considerable heterogeneity exists with regard to study design, adapted CBT type and intensity, and employed neuroimaging paradigms, all of which may partly explain the difference in studies’ outcomes. The lack of randomization and effective controls in most of them makes it difficult to draw formal conclusion whether the observed effects are CBT mediated or due to spontaneous recovery. Despite the observed inconsistencies and dearth of data, CBT appears to exert its anti-depressant effects mainly by modulating the function of affective and cognitive networks devoted to emotions generation and control, respectively. This concept remains to be validated in large scale randomized controlled trials. Full article
Open AccessReview Individualized Immunological Data for Precise Classification of OCD Patients
Brain Sci. 2018, 8(8), 149; https://doi.org/10.3390/brainsci8080149
Received: 16 May 2018 / Revised: 1 August 2018 / Accepted: 3 August 2018 / Published: 9 August 2018
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Abstract
Obsessive–compulsive disorder (OCD) affects about 2% of the general population, for which several etiological factors were identified. Important among these is immunological dysfunction. This review aims to show how immunology can inform specific etiological factors, and how distinguishing between these etiologies is important
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Obsessive–compulsive disorder (OCD) affects about 2% of the general population, for which several etiological factors were identified. Important among these is immunological dysfunction. This review aims to show how immunology can inform specific etiological factors, and how distinguishing between these etiologies is important from a personalized treatment perspective. We found discrepancies concerning cytokines, raising the hypothesis of specific immunological etiological factors. Antibody studies support the existence of a potential autoimmune etiological factor. Infections may also provoke OCD symptoms, and therefore, could be considered as specific etiological factors with specific immunological impairments. Finally, we underline the importance of distinguishing between different etiological factors since some specific treatments already exist in the context of immunological factors for the improvement of classic treatments. Full article
(This article belongs to the Special Issue New Research in Obsessive-Compulsive Disorder and Major Depression)
Open AccessReview The Expanding Role of Ketogenic Diets in Adult Neurological Disorders
Brain Sci. 2018, 8(8), 148; https://doi.org/10.3390/brainsci8080148
Received: 28 June 2018 / Revised: 1 August 2018 / Accepted: 2 August 2018 / Published: 8 August 2018
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Abstract
The current review highlights the evidence supporting the use of ketogenic diet therapies in the management of adult epilepsy, adult malignant glioma and Alzheimer’s disease. An overview of the scientific literature, both preclinical and clinical, in each area is presented and management strategies
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The current review highlights the evidence supporting the use of ketogenic diet therapies in the management of adult epilepsy, adult malignant glioma and Alzheimer’s disease. An overview of the scientific literature, both preclinical and clinical, in each area is presented and management strategies for addressing adverse effects and compliance are discussed. Full article
Open AccessReview Perinatal Hypoxic-Ischemic Encephalopathy and Neuroprotective Peptide Therapies: A Case for Cationic Arginine-Rich Peptides (CARPs)
Brain Sci. 2018, 8(8), 147; https://doi.org/10.3390/brainsci8080147
Received: 28 June 2018 / Revised: 25 July 2018 / Accepted: 1 August 2018 / Published: 7 August 2018
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Abstract
Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is
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Perinatal hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality and morbidity in neonates, with survivors suffering significant neurological sequelae including cerebral palsy, epilepsy, intellectual disability and autism spectrum disorders. While hypothermia is used clinically to reduce neurological injury following HIE, it is only used for term infants (>36 weeks gestation) in tertiary hospitals and improves outcomes in only 30% of patients. For these reasons, a more effective and easily administrable pharmacological therapeutic agent, that can be used in combination with hypothermia or alone when hypothermia cannot be applied, is urgently needed to treat pre-term (≤36 weeks gestation) and term infants suffering HIE. Several recent studies have demonstrated that cationic arginine-rich peptides (CARPs), which include many cell-penetrating peptides [CPPs; e.g., transactivator of transcription (TAT) and poly-arginine-9 (R9; 9-mer of arginine)], possess intrinsic neuroprotective properties. For example, we have demonstrated that poly-arginine-18 (R18; 18-mer of arginine) and its D-enantiomer (R18D) are neuroprotective in vitro following neuronal excitotoxicity, and in vivo following perinatal hypoxia-ischemia (HI). In this paper, we review studies that have used CARPs and other peptides, including putative neuroprotective peptides fused to TAT, in animal models of perinatal HIE. We critically evaluate the evidence that supports our hypothesis that CARP neuroprotection is mediated by peptide arginine content and positive charge and that CARPs represent a novel potential therapeutic for HIE. Full article
(This article belongs to the Special Issue The Treatment of Neonatal Hypoxic-Ischemic Encephalopathy)
Open AccessReview Reading Deficits in Intellectual Disability Are still an Open Question: A Narrative Review
Brain Sci. 2018, 8(8), 146; https://doi.org/10.3390/brainsci8080146
Received: 12 July 2018 / Revised: 2 August 2018 / Accepted: 3 August 2018 / Published: 7 August 2018
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Abstract
Background. In children with intellectual disability (ID), the acquisition of reading skills constitutes a basic step towards the possibility of independent living, social inclusion and participation. Methods. We carried out a narrative review of the literature on reading fluency and accuracy of individuals
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Background. In children with intellectual disability (ID), the acquisition of reading skills constitutes a basic step towards the possibility of independent living, social inclusion and participation. Methods. We carried out a narrative review of the literature on reading fluency and accuracy of individuals with ID resulting from different genetic syndromes (Fragile X, Williams, Velocardiofacial, Prader-Willi, and Down syndrome). Our aim was to define their reading profiles in light of the dual-route reading model. For this purpose, studies that examined both word and non-word reading in children with ID were included in the analysis. Results. Seventeen studies emerged based on the selection criteria. The results were different depending on the control group used. A deficit in reading non-words emerged in studies that used the reading-level match design but not when standardized scores were used, when controls were age-matched or when a mental age matching was used. Thus, a deficit in reading non-words emerged only in studies that used the reading-level match design. However, severe methodological criticisms were recently raised about the use of this matching design. Conclusions. In view of the methodological problems in using grade equivalents, it is premature to draw definite conclusions about the reading profile of children with ID resulting from different genetic syndromes. In any case, the reviewed evidence provides little support for the idea that children with ID have selective difficulty in phonological reading. Thus, the reading profile of children with ID remains an open question that needs to be investigated by means of methodologically sound research. Full article
(This article belongs to the Special Issue Dyslexia, Dysgraphia and Related Developmental Disorders)
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Open AccessArticle Clinical and Functional Characterization of the Recurrent TUBA1A p.(Arg2His) Mutation
Brain Sci. 2018, 8(8), 145; https://doi.org/10.3390/brainsci8080145
Received: 30 May 2018 / Revised: 6 July 2018 / Accepted: 17 July 2018 / Published: 7 August 2018
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Abstract
The TUBA1A gene encodes tubulin alpha-1A, a protein that is highly expressed in the fetal brain. Alpha- and beta-tubulin subunits form dimers, which then co-assemble into microtubule polymers: dynamic, scaffold-like structures that perform key functions during neurogenesis, neuronal migration, and cortical organisation. Mutations
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The TUBA1A gene encodes tubulin alpha-1A, a protein that is highly expressed in the fetal brain. Alpha- and beta-tubulin subunits form dimers, which then co-assemble into microtubule polymers: dynamic, scaffold-like structures that perform key functions during neurogenesis, neuronal migration, and cortical organisation. Mutations in TUBA1A have been reported to cause a range of brain malformations. We describe four unrelated patients with the same de novo missense mutation in TUBA1A, c.5G>A, p.(Arg2His), as found by next generation sequencing. Detailed comparison revealed similar brain phenotypes with mild variability. Shared features included developmental delay, microcephaly, hypoplasia of the cerebellar vermis, dysplasia or thinning of the corpus callosum, small pons, and dysmorphic basal ganglia. Two of the patients had bilateral perisylvian polymicrogyria. We examined the effects of the p.(Arg2His) mutation by computer-based protein structure modelling and heterologous expression in HEK-293 cells. The results suggest the mutation subtly impairs microtubule function, potentially by affecting inter-dimer interaction. Based on its sequence context, c.5G>A is likely to be a common recurrent mutation. We propose that the subtle functional effects of p.(Arg2His) may allow for other factors (such as genetic background or environmental conditions) to influence phenotypic outcome, thus explaining the mild variability in clinical manifestations. Full article
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Open AccessArticle Conventional Structural Magnetic Resonance Imaging in Differentiating Chronic Disorders of Consciousness
Brain Sci. 2018, 8(8), 144; https://doi.org/10.3390/brainsci8080144
Received: 9 July 2018 / Revised: 26 July 2018 / Accepted: 3 August 2018 / Published: 5 August 2018
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Abstract
Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and
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Differential diagnosis of unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS) is one of the most challenging problems for specialists who deal with chronic disorders of consciousness (DOC). The aim of the current study was to develop a conventional MRI-based scale and to evaluate its role in distinguishing chronic disorders of consciousness (Disorders of Consciousness MRI-based Distinguishing Scale, DOC-MRIDS). Data were acquired from 30 patients with clinically diagnosed chronic disorders of consciousness. All patients underwent conventional MRI using a Siemens Verio 3.0 T scanner, which included T2 and T1 sequences for patient assessment. Diffuse cortical atrophy, ventricular enlargement, sulcal widening, leukoaraiosis, brainstem and/or thalamus degeneration, corpus callosum degeneration, and corpus callosum lesions were assessed according to DOC-MRIDS criteria, with a total score calculation. The ROC-analysis showed that a reasonable threshold DOC-MRIDS total score was 5.5, that is, patients with DOC-MRIDS total score of 6 and above were classified as UWS and 5 and below as MCS, with sensitivity of 82.4% and specificity of 92.3%. The novel structural MRI-based scale for the assessment of typical brain lesions in patients with chronic DOC is relatively easy to apply, and provides good specificity and sensitivity values for discrimination between UWS and MCS. Full article
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Open AccessArticle New Insights into GFAP Negative Astrocytes in Calbindin D28k Immunoreactive Astrocytes
Brain Sci. 2018, 8(8), 143; https://doi.org/10.3390/brainsci8080143
Received: 26 May 2018 / Revised: 27 July 2018 / Accepted: 31 July 2018 / Published: 3 August 2018
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Abstract
Glial fibrillary acidic protein (GFAP) is commonly used as a specific marker for the identification of astrocytes. Nevertheless, it is known from the literature that astrocytes in situ in contrast to cultured astrocytes may feature lower levels of GFAP. In order to characterize
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Glial fibrillary acidic protein (GFAP) is commonly used as a specific marker for the identification of astrocytes. Nevertheless, it is known from the literature that astrocytes in situ in contrast to cultured astrocytes may feature lower levels of GFAP. In order to characterize the properties of GFAP in Calbindin D28k immunoreactive astrocytes, we use primary astrocyte cultures from cells of new-born mice. A double fluorescence immunocytochemical analysis reveals that GFAP in cultured Calbindin D28k astrocytes behaves differently depending on whether the medium contains foetal bovine serum (FBS) or not. The novelty in our study is, however, that a high percentage of Calbindin D28k cultured astrocytes in a medium with 10% FBS are GFAP negative. In addition, the study shows that Calbindin D28k astrocytes have (i) a different morphology and (ii) a higher concentration of Calbindin D28k in the nucleus than in the cytoplasm. The study provides new evidence that in order to fully understand the characteristics of astrocytes, astrocytes which are Calbindin D28k positive have to be investigated. Full article
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Open AccessReview Patient-Derived Stem Cell Models in SPAST HSP: Disease Modelling and Drug Discovery
Brain Sci. 2018, 8(8), 142; https://doi.org/10.3390/brainsci8080142
Received: 15 June 2018 / Revised: 18 July 2018 / Accepted: 25 July 2018 / Published: 31 July 2018
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Abstract
Hereditary spastic paraplegia is an inherited, progressive paralysis of the lower limbs first described by Adolph Strümpell in 1883 with a further detailed description of the disease by Maurice Lorrain in 1888. Today, more than 100 years after the first case of HSP
[...] Read more.
Hereditary spastic paraplegia is an inherited, progressive paralysis of the lower limbs first described by Adolph Strümpell in 1883 with a further detailed description of the disease by Maurice Lorrain in 1888. Today, more than 100 years after the first case of HSP was described, we still do not know how mutations in HSP genes lead to degeneration of the corticospinal motor neurons. This review describes how patient-derived stem cells contribute to understanding the disease mechanism at the cellular level and use this for discovery of potential new therapeutics, focusing on SPAST mutations, the most common cause of HSP. Full article
(This article belongs to the Special Issue Advances in Genetics of Hereditary Spastic Paraplegia)
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Open AccessArticle Effect of Chronic Administration of Nickel on Affective and Cognitive Behavior in Male and Female Rats: Possible Implication of Oxidative Stress Pathway
Brain Sci. 2018, 8(8), 141; https://doi.org/10.3390/brainsci8080141
Received: 6 June 2018 / Revised: 22 June 2018 / Accepted: 2 July 2018 / Published: 31 July 2018
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Abstract
Nickel (Ni) toxicity has been reported to produce biochemical and behavioral dysfunction. The present study was undertaken to examine whether Ni chronic administration can induce alterations of affective and cognitive behavior and oxidative stress in male and female rats. Twenty-four rats, for each
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Nickel (Ni) toxicity has been reported to produce biochemical and behavioral dysfunction. The present study was undertaken to examine whether Ni chronic administration can induce alterations of affective and cognitive behavior and oxidative stress in male and female rats. Twenty-four rats, for each gender, divided into control and three test groups (n = 6), were injected intraperitoneally with saline (0.9% NaCl) or NiCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. The Morris Water Maze was used to evaluate the spatial learning and memory. The hippocampus of each animal was taken for biochemical examination. The results showed that Ni administration dose dependently increased anxiety-like behavior in both tests. A significant increase in depression-like symptoms was also exhibited by Ni treated rats. In the Morris Water Maze test, the spatial learning and memory were significantly impaired just in males treated with 1 mg/kg of Ni. With regard to biochemical analysis, activity of catalase (CAT) and superoxide dismutase (SOD) were significantly decreased, while the levels of nitric oxide (NO) and lipid peroxidation (LPO) in the hippocampus were significantly increased in the Ni-treated groups. Consequently, chronic Ni administration induced behavioral and biochemical dysfunctions. Full article
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Open AccessArticle Does School Racial Composition Explain Why High Income Black Youth Perceive More Discrimination? A Gender Analysis
Brain Sci. 2018, 8(8), 140; https://doi.org/10.3390/brainsci8080140
Received: 11 July 2018 / Revised: 20 July 2018 / Accepted: 26 July 2018 / Published: 30 July 2018
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Abstract
Recent research has documented poor mental health among high socioeconomic status (SES) Blacks, particularly African American males. The literature has also shown a positive link between SES and perceived discrimination, suggesting that perceived discrimination may explain why high SES Black males report poor
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Recent research has documented poor mental health among high socioeconomic status (SES) Blacks, particularly African American males. The literature has also shown a positive link between SES and perceived discrimination, suggesting that perceived discrimination may explain why high SES Black males report poor mental health. To better understand the role of contextual factors in explaining this pattern, we aimed to test whether school racial composition explains why high income Black youth perceive more discrimination. We explored these associations by ethnicity and gender. Using data from the National Survey of American Life-Adolescent supplement (NSAL-A), the current study included 810 African American and 360 Caribbean Black youth, with a mean age of 15. Ethnicity, age, gender, income-to-needs ratio (SES), skin color, school racial composition, and perceived (daily) discrimination were measured. Using Stata 15.0 (Stata Corp., College Station, TX, USA), we fitted seven structural equation models (SEMs) for data analysis in the pooled sample based on the intersection of ethnicity and gender. Considerable gender by ethnicity variations were found in the associations between SES, school racial composition, and perceived discrimination. For African American males but not African American females or Caribbean Black males or females, school racial composition fully mediated the effect of SES on perceived discrimination. The role of inter-racial contact as a mechanism for high discrimination and poor mental health of Black American adolescents may depend on their intersection of ethnicity and gender. School racial composition may be a mechanism for increased perceived discrimination among high SES African American males. Full article
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Open AccessArticle Workplace Racial Composition Explains High Perceived Discrimination of High Socioeconomic Status African American Men
Brain Sci. 2018, 8(8), 139; https://doi.org/10.3390/brainsci8080139
Received: 14 June 2018 / Revised: 13 July 2018 / Accepted: 13 July 2018 / Published: 27 July 2018
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Abstract
Background: Sociological and epidemiological literature have both shown that socioeconomic status (SES) protects populations and individuals against health problems. Recent research, however, has shown that African Americans gain less from their SES and African Americans of high SES, particularly males, may be vulnerable
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Background: Sociological and epidemiological literature have both shown that socioeconomic status (SES) protects populations and individuals against health problems. Recent research, however, has shown that African Americans gain less from their SES and African Americans of high SES, particularly males, may be vulnerable to perceived discrimination, as explained by the Minorities’ Diminished Returns theory. One potential mechanism for this phenomenon is that high SES African Americans have a higher tendency to work in predominantly White workplaces, which increases their perceived discrimination. It is, however, unknown if the links between SES, working in predominantly White work groups and perceived discrimination differ for male and female African Americans. Aim: To test the associations between SES, workplace racial composition and perceived discrimination in a nationally representative sample of male and female African American adults. Methods. This study included a total number of 1775 employed African American adults who were either male (n = 676) or female (n = 1099), all enrolled from the National Survey of American Life (NSAL). The study measured gender, age, SES (educational attainment and household income), workplace racial composition and perceived discrimination. Structural Equation Modeling (SEM) was applied in the overall sample and also by gender. Results: In the pooled sample that included both genders, high education and household income were associated with working in a predominantly White work group, which was in turn associated with more perceived discrimination. We did not find gender differences in the associations between SES, workplace racial composition and perceived discrimination. Conclusion: Although racial composition of workplace may be a mechanism by which high SES increases discriminatory experiences for African Americans, males and females may not differ in this regard. Policies are needed to reduce discrimination in racially diverse workplaces. This is particularly the case for African Americans who work in predominantly White work environments. Full article
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Open AccessReview Spinal Cord Stimulation for Neuropathic Pain: Current Trends and Future Applications
Brain Sci. 2018, 8(8), 138; https://doi.org/10.3390/brainsci8080138
Received: 30 June 2018 / Accepted: 18 July 2018 / Published: 24 July 2018
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Abstract
The origin and the neural pathways involved in chronic neuropathic pain are still not extensively understood. For this reason, despite the wide variety of pain medications available on the market, neuropathic pain is challenging to treat. The present therapeutic alternative considered as the
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The origin and the neural pathways involved in chronic neuropathic pain are still not extensively understood. For this reason, despite the wide variety of pain medications available on the market, neuropathic pain is challenging to treat. The present therapeutic alternative considered as the gold standard for many kinds of chronic neuropathic pain is epidural spinal cord stimulation (SCS). Despite its proved efficacy, the favourable cost-effectiveness when compared to the long-term use of poorly effective drugs and the expanding array of indications and technical improvements, SCS is still worldwide largely neglected by general practitioners, neurologists, neurosurgeons and pain therapists, often bringing to a large delay in considering as a therapeutic option for patients affected by neuropathic chronic pain. The present state of the art of SCS in the treatment of chronic neuropathic pain is here overviewed and speculations on whether to use a trial period or direct implant, to choose between percutaneous leads or paddle electrodes and on the pros and cons of the different patterns of stimulation presently available on the market (tonic stim, high-frequency stim and burst stim) are described. Full article
(This article belongs to the Special Issue Neuromodulation for Intractable Pain)
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