Brain Sciences

8 pages, 297 KiB

Open AccessArticle

Morning Headache as an Obstructive Sleep Apnea-Related Symptom among Sleep Clinic Patients—A Cross-Section Analysis

by Jakub Spałka, Konrad Kędzia, Wojciech Kuczyński, Aleksandra Kudrycka, Aleksandra Małolepsza, Piotr Białasiewicz and Łukasz Mokros

Brain Sci. 2020, 10(1), 57; https://doi.org/10.3390/brainsci10010057 - 19 Jan 2020

Cited by 16 | Viewed by 6229

Abstract

Morning headache is considered to be a symptom of obstructive sleep apnea syndrome (OSAS). Despite not being as common as excessive daytime sleepiness or unrefreshing sleep, it can similarly impair everyday activities. The aim of the present study was to evaluate the prevalence [...] Read more.

Morning headache is considered to be a symptom of obstructive sleep apnea syndrome (OSAS). Despite not being as common as excessive daytime sleepiness or unrefreshing sleep, it can similarly impair everyday activities. The aim of the present study was to evaluate the prevalence of and factors associated with morning headaches (MH) among patients referred for polysomnography due to suspected OSAS. This is a retrospective study on 1131 patients who underwent polysomnography between 2013 and 2015. Morning headaches (MH) were reported in 29% of them. In a logistic regression model, a rise in the n probability of MH was associated with female sex (odds ratio, OR, 1.38, 95% confidence interval, CI, 1.08–1.75), history of hypertension (OR 1.25, 95% CI 1.06–1.46), complaint on unrefreshing sleep (OR 1.42, 95% CI 1.19–1.70), choking at night (OR 1.25, 95% CI 1.05–1.49), and fall in total sleep time (OR 0.872 per each hour, 95% CI 0.76–0.99). The risk between MH and apnea–hypopnea index, blood oxygen saturation parameters or arousal index was found to be statistically insignificant. There is a lack of evidence that MH is associated with the severity of OSAS or nocturnal hypoxemia. Full article

(This article belongs to the Special Issue Disturbances of Sleep Among Older People)

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29 pages, 986 KiB

Open AccessReview

Neurofilaments: The C-Reactive Protein of Neurology

by Kate L. Lambertsen, Catarina B. Soares, David Gaist and Helle H. Nielsen

Brain Sci. 2020, 10(1), 56; https://doi.org/10.3390/brainsci10010056 - 18 Jan 2020

Cited by 52 | Viewed by 7327

Abstract

Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is [...] Read more.

Neurofilaments (NFs) are quickly becoming the biomarkers of choice in the field of neurology, suggesting their use as an unspecific screening marker, much like the use of elevated plasma C-reactive protein (CRP) in other fields. With sensitive techniques being readily available, evidence is growing regarding the diagnostic and prognostic value of NFs in many neurological disorders. Here, we review the latest literature on the structure and function of NFs and report the strengths and pitfalls of NFs as markers of neurodegeneration in the context of neurological diseases of the central and peripheral nervous systems. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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21 pages, 2683 KiB

Open AccessArticle

Motor Program Transformation of Throwing Dart from the Third-Person Perspective

by Alexey Tumialis, Alexey Smirnov, Kirill Fadeev, Tatiana Alikovskaia, Pavel Khoroshikh, Alexander Sergievich and Kirill Golokhvast

Brain Sci. 2020, 10(1), 55; https://doi.org/10.3390/brainsci10010055 - 18 Jan 2020

Cited by 7 | Viewed by 4514

Abstract

The perspective of perceiving one’s action affects its speed and accuracy. In the present study, we investigated the change in accuracy and kinematics when subjects throw darts from the first-person perspective and the third-person perspective with varying angles of view. To model the [...] Read more.

The perspective of perceiving one’s action affects its speed and accuracy. In the present study, we investigated the change in accuracy and kinematics when subjects throw darts from the first-person perspective and the third-person perspective with varying angles of view. To model the third-person perspective, subjects were looking at themselves as well as the scene through the virtual reality head-mounted display (VR HMD). The scene was supplied by a video feed from the camera located to the up and 0, 20 and 40 degrees to the right behind the subjects. The 28 subjects wore a motion capture suit to register their right hand displacement, velocity and acceleration, as well as torso rotation during the dart throws. The results indicated that mean accuracy shifted in opposite direction with the changes of camera location in vertical axis and in congruent direction in horizontal axis. Kinematic data revealed a smaller angle of torso rotation to the left in all third-person perspective conditions before and during the throw. The amplitude, speed and acceleration in third-person condition were lower compared to the first-person view condition, before the peak velocity of the hand in the direction toward the target and after the peak velocity in lowering the hand. Moreover, the hand movement angle was smaller in the third-person perspective conditions with 20 and 40 angle of view, compared with the first-person perspective condition just preceding the time of peak velocity, and the difference between conditions predicted the changes in mean accuracy of the throws. Thus, the results of this study revealed that subject’s localization contributed to the transformation of the motor program. Full article

(This article belongs to the Special Issue The Role of Body in Brain Plasticity)

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17 pages, 7082 KiB

Open AccessReply

On the Role of Contrast Polarity: In Response to van der Helm’s Comments

by Baingio Pinna and Livio Conti

Brain Sci. 2020, 10(1), 54; https://doi.org/10.3390/brainsci10010054 - 17 Jan 2020

Cited by 3 | Viewed by 3031

Abstract

In this work, we discussed and counter-commented van der Helm’s comments on our previous paper (Pinna and Conti, Brain Sci., 2019, 9, 149), where we demonstrated unique and relevant visual properties imparted by contrast polarity in eliciting amodal completion. The [...] Read more.

In this work, we discussed and counter-commented van der Helm’s comments on our previous paper (Pinna and Conti, Brain Sci., 2019, 9, 149), where we demonstrated unique and relevant visual properties imparted by contrast polarity in eliciting amodal completion. The main question we addressed was: “What is the role of shape formation and perceptual organization in inducing amodal completion?” To answer this question, novel stimuli were studied through Gestalt experimental phenomenology. The results demonstrated the domination of the contrast polarity against good continuation, T-junctions, and regularity. Moreover, the limiting conditions explored revealed a new kind of junction next to the T- and Y-junctions, respectively responsible for amodal completion and tessellation. We called them I-junctions. The results were theoretically discussed in relation to the previous approaches and in the light of the phenomenal salience imparted by contrast polarity. In counter-commenting van der Helm’s comments we went into detail of his critiques and rejected all of them point-by-point. We proceeded by summarizing hypotheses and discussion of the previous work, then commenting on each critique through old and new phenomena and clarifying the meaning of our previous conclusions. Full article

(This article belongs to the Special Issue Vividness, Consciousness, and Mental Imagery: Making the Missing Links across Disciplines and Methods)

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10 pages, 909 KiB

Open AccessArticle

Caucasian Infants’ Attentional Orienting to Own- and Other-Race Faces

by Jonathan E. Prunty, Kelsey C. Jackson, Jolie. R. Keemink and David J. Kelly

Brain Sci. 2020, 10(1), 53; https://doi.org/10.3390/brainsci10010053 - 17 Jan 2020

Cited by 12 | Viewed by 4079

Abstract

Infants show preferential attention toward faces and detect faces embedded within complex naturalistic scenes. Newborn infants are insensitive to race, but rapidly develop differential processing of own- and other-race faces. In the present study, we investigated the development of attentional orienting toward own- [...] Read more.

Infants show preferential attention toward faces and detect faces embedded within complex naturalistic scenes. Newborn infants are insensitive to race, but rapidly develop differential processing of own- and other-race faces. In the present study, we investigated the development of attentional orienting toward own- and other-race faces embedded within naturalistic scenes. Infants aged six-, nine- and twelve-months did not show differences in the speed of orienting to own- and other race faces, but other-race faces held infants’ visual attention for longer. We also found a clear developmental progression in attentional capture and holding, with older infants orienting to faces faster and fixating them for longer. Results are interpreted within the context of the two-process model of face processing. Full article

(This article belongs to the Special Issue The Study of Eye Movements in Infancy)

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13 pages, 1823 KiB

Open AccessArticle

Impaired Expression of Tetraspanin 32 (TSPAN32) in Memory T Cells of Patients with Multiple Sclerosis

by Maria Sofia Basile, Emanuela Mazzon, Katia Mangano, Manuela Pennisi, Maria Cristina Petralia, Salvo Danilo Lombardo, Ferdinando Nicoletti, Paolo Fagone and Eugenio Cavalli

Brain Sci. 2020, 10(1), 52; https://doi.org/10.3390/brainsci10010052 - 17 Jan 2020

Cited by 14 | Viewed by 4076

Abstract

Tetraspanins are a conserved family of proteins involved in a number of biological processes. We have previously shown that Tetraspanin-32 (TSPAN32) is significantly downregulated upon activation of T helper cells via anti-CD3/CD28 stimulation. On the other hand, TSPAN32 is marginally modulated in activated [...] Read more.

Tetraspanins are a conserved family of proteins involved in a number of biological processes. We have previously shown that Tetraspanin-32 (TSPAN32) is significantly downregulated upon activation of T helper cells via anti-CD3/CD28 stimulation. On the other hand, TSPAN32 is marginally modulated in activated Treg cells. A role for TSPAN32 in controlling the development of autoimmune responses is consistent with our observation that encephalitogenic T cells from myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) mice exhibit significantly lower levels of TSPAN32 as compared to naïve T cells. In the present study, by making use of ex vivo and in silico analysis, we aimed to better characterize the pathophysiological and diagnostic/prognostic role of TSPAN32 in T cell immunity and in multiple sclerosis (MS). We first show that TSPAN32 is significantly downregulated in memory T cells as compared to naïve T cells, and that it is further diminished upon ex vivo restimulation. Accordingly, following antigenic stimulation, myelin-specific memory T cells from MS patients showed significantly lower expression of TSPAN32 as compared to memory T cells from healthy donors (HD). The expression levels of TSPAN32 was significantly downregulated in peripheral blood mononuclear cells (PBMCs) from drug-naïve MS patients as compared to HD, irrespective of the disease state. Finally, when comparing patients undergoing early relapses in comparison to patients with longer stable disease, moderate but significantly lower levels of TSPAN32 expression were observed in PBMCs from the former group. Our data suggest a role for TSPAN32 in the immune responses underlying the pathophysiology of MS and represent a proof-of-concept for additional studies aiming at dissecting the eventual contribution of TSPAN32 in other autoimmune diseases and its possible use of TSPAN32 as a diagnostic factor and therapeutic target. Full article

(This article belongs to the Special Issue Advances in Multiple Sclerosis Research—Series I)

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8 pages, 227 KiB

Open AccessPerspective

A New Treatment Opportunity for DIPG and Diffuse Midline Gliomas: 5-ALA Augmented Irradiation, the 5aai Regimen

by Richard E. Kast, Alex P. Michael, Iacopo Sardi, Terry C. Burns, Tim Heiland, Georg Karpel-Massler, Francois G. Kamar and Marc-Eric Halatsch

Brain Sci. 2020, 10(1), 51; https://doi.org/10.3390/brainsci10010051 - 17 Jan 2020

Cited by 9 | Viewed by 4470

Abstract

Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a [...] Read more.

Prognosis for diffuse intrinsic pontine glioma (DIPG) and generally for diffuse midline gliomas (DMG) has only marginally improved over the last ~40 years despite dozens of chemotherapy and other therapeutic trials. The prognosis remains invariably fatal. We present here the rationale for a planned study of adding 5-aminolevulinic acid (5-ALA) to the current irradiation of DIPG or DMG: the 5aai regimen. In a series of recent papers, oral 5-ALA was shown to enhance standard therapeutic ionizing irradiation. 5-ALA is currently used in glioblastoma surgery to enable demarcation of overt tumor margins by virtue of selective uptake of 5-ALA by neoplastic cells and selective conversion to protoporphyrin IX (PpIX), which fluoresces after excitation by 410 nm (blue) light. 5-ALA is also useful in treating glioblastomas by virtue of PpIX’s transfer of energy to O₂ molecules, producing a singlet oxygen that in turn oxidizes intracellular DNA, lipids, and proteins, resulting in selective malignant cell cytotoxicity. This is called photodynamic treatment (PDT). Shallow penetration of light required for PpIX excitation and resultant energy transfer to O₂ and cytotoxicity results in the inaccessibility of central structures like the pons or thalamus to sufficient light. The recent demonstration that keV and MeV photons can also excite PpIX and generate singlet O₂ allows for reconsideration of 5-ALA PDT for treating DMG and DIPG. 5-ALA has an eminently benign side effect profile in adults and children. A pilot study in DIPG/DMG of slow uptitration of 5-ALA prior to each standard irradiation session—the 5aai regimen—is warranted. Full article

(This article belongs to the Special Issue Tumour Microenvironment in Paediatric Brain Tumour)

11 pages, 324 KiB

Open AccessComment

Dubious Claims about Simplicity and Likelihood: Comment on Pinna and Conti (2019)

by Peter A. van der Helm

Brain Sci. 2020, 10(1), 50; https://doi.org/10.3390/brainsci10010050 - 16 Jan 2020

Cited by 4 | Viewed by 3956

Abstract

Pinna and Conti (Brain Sci., 2019, 9, 149, doi:10.3390/brainsci9060149) presented phenomena concerning the salience and role of contrast polarity in human visual perception, particularly in amodal completion. These phenomena are indeed illustrative thereof, but here, the focus is on their [...] Read more.

Pinna and Conti (Brain Sci., 2019, 9, 149, doi:10.3390/brainsci9060149) presented phenomena concerning the salience and role of contrast polarity in human visual perception, particularly in amodal completion. These phenomena are indeed illustrative thereof, but here, the focus is on their claims (1) that neither simplicity nor likelihood approaches can account for these phenomena; and (2) that simplicity and likelihood are equivalent. I argue that their first claim is based on incorrect assumptions, whereas their second claim is simply untrue. Full article

(This article belongs to the Special Issue Vividness, Consciousness, and Mental Imagery: Making the Missing Links across Disciplines and Methods)

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12 pages, 241 KiB

Open AccessArticle

Polypharmacy Is Associated with Lower Memory Function in African American Older Adults

by Shervin Assari, Cheryl Wisseh, Mohammed Saqib and Mohsen Bazargan

Brain Sci. 2020, 10(1), 49; https://doi.org/10.3390/brainsci10010049 - 16 Jan 2020

Cited by 11 | Viewed by 4258

Abstract

Although previous research has linked polypharmacy to lower cognitive function in the general population, we know little about this association among economically challenged African American (AA) older adults. This study explored the link between polypharmacy and memory function among AA older adults. This [...] Read more.

Although previous research has linked polypharmacy to lower cognitive function in the general population, we know little about this association among economically challenged African American (AA) older adults. This study explored the link between polypharmacy and memory function among AA older adults. This community-based study recruited 399 AA older adults who were 65+ years old and living in economically disadvantaged areas of South Los Angeles. Polypharmacy (taking 5+ medications) was the independent variable, memory function was the outcome variable (continuous variable), and gender, age, living arrangement, socioeconomic status (educational attainment and financial strain), health behaviors (current smoking and any binge drinking), and multimorbidity (number of chronic diseases) were the covariates. Linear regression was used for data analyses. Polypharmacy was associated with lower scores on memory function, above and beyond covariates. Among AA older adults, polypharmacy may be linked to worse cognitive function. Future research should test the mechanisms by which polypharmacy is associated with lower levels of cognitive decline. There is a need for screening for memory problems in AA older adults who are exposed to polypharmacy. Full article

(This article belongs to the Special Issue Dementia and Cognitive Ageing)

22 pages, 4215 KiB

Open AccessArticle

Neurophysiological Vigilance Characterisation and Assessment: Laboratory and Realistic Validations Involving Professional Air Traffic Controllers

by Marika Sebastiani, Gianluca Di Flumeri, Pietro Aricò, Nicolina Sciaraffa, Fabio Babiloni and Gianluca Borghini

Brain Sci. 2020, 10(1), 48; https://doi.org/10.3390/brainsci10010048 - 15 Jan 2020

Cited by 21 | Viewed by 4239

Abstract

Vigilance degradation usually causes significant performance decrement. It is also considered the major factor causing the out-of-the-loop phenomenon (OOTL) occurrence. OOTL is strongly related to a high level of automation in operative contexts such as the Air Traffic Management (ATM), and it could [...] Read more.

Vigilance degradation usually causes significant performance decrement. It is also considered the major factor causing the out-of-the-loop phenomenon (OOTL) occurrence. OOTL is strongly related to a high level of automation in operative contexts such as the Air Traffic Management (ATM), and it could lead to a negative impact on the Air Traffic Controllers’ (ATCOs) engagement. As a consequence, being able to monitor the ATCOs’ vigilance would be very important to prevent risky situations. In this context, the present study aimed to characterise and assess the vigilance level by using electroencephalographic (EEG) measures. The first study, involving 13 participants in laboratory settings allowed to find out the neurophysiological features mostly related to vigilance decrements. Those results were also confirmed under realistic ATM settings recruiting 10 professional ATCOs. The results demonstrated that (i) there was a significant performance decrement related to vigilance reduction; (ii) there were no substantial differences between the identified neurophysiological features in controlled and ecological settings, and the EEG-channel configuration defined in laboratory was able to discriminate and classify vigilance changes in ATCOs’ vigilance with high accuracy (up to 84%); (iii) the derived two EEG-channel configuration was able to assess vigilance variations reporting only slight accuracy reduction. Full article

(This article belongs to the Special Issue Brain Plasticity, Cognitive Training and Mental States Assessment)

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14 pages, 338 KiB

Open AccessEditorial

Acknowledgement to Reviewers of Brain Science in 2019

by Brain Science Editorial Office

Brain Sci. 2020, 10(1), 47; https://doi.org/10.3390/brainsci10010047 - 15 Jan 2020

Viewed by 2514

Abstract

The editorial team greatly appreciates the reviewers who have dedicated their considerable time and expertise to the journal’s rigorous editorial process over the past 12 months, regardless of whether the papers are finally published or not [...] Full article

20 pages, 3124 KiB

Open AccessArticle

On Assessing Driver Awareness of Situational Criticalities: Multi-modal Bio-Sensing and Vision-Based Analysis, Evaluations, and Insights

by Siddharth Siddharth and Mohan M. Trivedi

Brain Sci. 2020, 10(1), 46; https://doi.org/10.3390/brainsci10010046 - 15 Jan 2020

Cited by 6 | Viewed by 3661

Abstract

Automobiles for our roadways are increasingly using advanced driver assistance systems. The adoption of such new technologies requires us to develop novel perception systems not only for accurately understanding the situational context of these vehicles, but also to infer the driver’s awareness in [...] Read more.

Automobiles for our roadways are increasingly using advanced driver assistance systems. The adoption of such new technologies requires us to develop novel perception systems not only for accurately understanding the situational context of these vehicles, but also to infer the driver’s awareness in differentiating between safe and critical situations. This manuscript focuses on the specific problem of inferring driver awareness in the context of attention analysis and hazardous incident activity. Even after the development of wearable and compact multi-modal bio-sensing systems in recent years, their application in driver awareness context has been scarcely explored. The capability of simultaneously recording different kinds of bio-sensing data in addition to traditionally employed computer vision systems provides exciting opportunities to explore the limitations of these sensor modalities. In this work, we explore the applications of three different bio-sensing modalities namely electroencephalogram (EEG), photoplethysmogram (PPG) and galvanic skin response (GSR) along with a camera-based vision system in driver awareness context. We assess the information from these sensors independently and together using both signal processing- and deep learning-based tools. We show that our methods outperform previously reported studies to classify driver attention and detecting hazardous/non-hazardous situations for short time scales of two seconds. We use EEG and vision data for high resolution temporal classification (two seconds) while additionally also employing PPG and GSR over longer time periods. We evaluate our methods by collecting user data on twelve subjects for two real-world driving datasets among which one is publicly available (KITTI dataset) while the other was collected by us (LISA dataset) with the vehicle being driven in an autonomous mode. This work presents an exhaustive evaluation of multiple sensor modalities on two different datasets for attention monitoring and hazardous events classification. Full article

(This article belongs to the Special Issue Brain Plasticity, Cognitive Training and Mental States Assessment)

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12 pages, 2481 KiB

Open AccessArticle

Improvements of Motor Performances in the Drosophila LRRK2 Loss-of-Function Model of Parkinson’s Disease: Effects of Dialyzed Leucocyte Extracts from Human Serum

by Andrea Diana, Maria Collu, Maria Antonietta Casu, Ignazia Mocci, Miguel Aguilar-Santelises and Maria Dolores Setzu

Brain Sci. 2020, 10(1), 45; https://doi.org/10.3390/brainsci10010045 - 14 Jan 2020

Cited by 2 | Viewed by 3474

Abstract

Within neurodegenerative syndromes, Parkinson’s disease (PD) is typically associated with its locomotor defects, sleep disturbances and related dopaminergic (DA) neuron loss. The fruit fly, Drosophila melanogaster (D. melanogaster), with leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 [...] Read more.

Within neurodegenerative syndromes, Parkinson’s disease (PD) is typically associated with its locomotor defects, sleep disturbances and related dopaminergic (DA) neuron loss. The fruit fly, Drosophila melanogaster (D. melanogaster), with leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 domain, provides mechanistic insights into corresponding human behaviour, possibly disclosing some physiopathologic features of PD in both genetic and sporadic forms. Moreover, several data support the boosting impact of innate and adaptive immunity pathways for driving the progression of PD. In this context, human dialyzable leukocyte extracts (DLE) have been extensively used to transfer antigen-specific information that influences the activity of various immune components, including inflammatory cytokines. Hence, the main goal of our study was to ascertain the therapeutic potential of DLE from male and female donors on D. melanogaster LRRK2 loss-of-function, as compared to D. melanogaster wild-type (WT), in terms of rescuing physiological parameters, such as motor and climbing activities, which are severely compromised in the mutant flies. Finally, in search of the anatomical structures responsible for restored functions in parkinsonian-like mutant flies, we found a topographical correlation between improvement of locomotor performances and an increased number of dopaminergic neurons in selective areas of LRRK2 mutant brains. Full article

(This article belongs to the Section Molecular and Cellular Neuroscience)

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17 pages, 1526 KiB

Open AccessArticle

Pharmacological Mechanisms Involved in Sensory Gating Disruption Induced by (±)-3,4-Methylene- Dioxymethamphetamine (MDMA): Relevance to Schizophrenia

by Jaime Lee, Shane Thwaites, Andrea Gogos and Maarten van den Buuse

Brain Sci. 2020, 10(1), 44; https://doi.org/10.3390/brainsci10010044 - 13 Jan 2020

Cited by 3 | Viewed by 3516

Abstract

Sensory gating deficits have been demonstrated in schizophrenia, but the mechanisms involved remain unclear. In the present study, we used disruption of paired-pulse gating of evoked potentials in rats by the administration of (±)-3,4-methylene-dioxymethamphetamine (MDMA) to study serotonergic and dopaminergic mechanisms involved in [...] Read more.

Sensory gating deficits have been demonstrated in schizophrenia, but the mechanisms involved remain unclear. In the present study, we used disruption of paired-pulse gating of evoked potentials in rats by the administration of (±)-3,4-methylene-dioxymethamphetamine (MDMA) to study serotonergic and dopaminergic mechanisms involved in auditory sensory gating deficits. Male Sprague-Dawley rats were instrumented with cortical surface electrodes to record evoked potential changes in response to pairs of 85dB tones (S1 and S2), 500msec apart. Administration of MDMA eliminated the normal reduction in the amplitude of S2 compared to S1, representing disruption of auditory sensory gating. Pretreatment of the animals with the dopamine D1 receptor antagonist, SCH23390, the dopamine D2 receptor antagonist, haloperidol, the serotonin (5-HT)1A receptor antagonist, WAY100635, or the 5-HT2A receptor antagonist, ketanserin, all blocked the effect of MDMA, although the drugs differentially affected the individual S1 and S2 amplitudes. These data show involvement of both dopaminergic and serotonergic mechanisms in disruption of auditory sensory gating by MDMA. These and previous results suggest that MDMA targets serotonergic pathways, involving both 5-HT1A and 5-HT2A receptors, leading to dopaminergic activation, involving both D1 and D2 receptors, and ultimately sensory gating deficits. It is speculated that similar interactive mechanisms are affected in schizophrenia. Full article

(This article belongs to the Section Systems Neuroscience)

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20 pages, 2513 KiB

Open AccessReview

Therapeutic Advances for Huntington’s Disease

by Ashok Kumar, Vijay Kumar, Kritanjali Singh, Sukesh Kumar, You-Sam Kim, Yun-Mi Lee and Jong-Joo Kim

Brain Sci. 2020, 10(1), 43; https://doi.org/10.3390/brainsci10010043 - 12 Jan 2020

Cited by 74 | Viewed by 13143

Abstract

Huntington’s disease (HD) is a progressive neurological disease that is inherited in an autosomal fashion. The cause of disease pathology is an expansion of cytosine-adenine-guanine (CAG) repeats within the huntingtin gene (HTT) on chromosome 4 (4p16.3), which codes the huntingtin protein [...] Read more.

Huntington’s disease (HD) is a progressive neurological disease that is inherited in an autosomal fashion. The cause of disease pathology is an expansion of cytosine-adenine-guanine (CAG) repeats within the huntingtin gene (HTT) on chromosome 4 (4p16.3), which codes the huntingtin protein (mHTT). The common symptoms of HD include motor and cognitive impairment of psychiatric functions. Patients exhibit a representative phenotype of involuntary movement (chorea) of limbs, impaired cognition, and severe psychiatric disturbances (mood swings, depression, and personality changes). A variety of symptomatic treatments (which target glutamate and dopamine pathways, caspases, inhibition of aggregation, mitochondrial dysfunction, transcriptional dysregulation, and fetal neural transplants, etc.) are available and some are in the pipeline. Advancement in novel therapeutic approaches include targeting the mutant huntingtin (mHTT) protein and the HTT gene. New gene editing techniques will reduce the CAG repeats. More appropriate and readily tractable treatment goals, coupled with advances in analytical tools will help to assess the clinical outcomes of HD treatments. This will not only improve the quality of life and life span of HD patients, but it will also provide a beneficial role in other inherited and neurological disorders. In this review, we aim to discuss current therapeutic research approaches and their possible uses for HD. Full article

(This article belongs to the Special Issue Juvenile Onset Huntington's Disease)

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19 pages, 366 KiB

Open AccessPerspective

Toward Improving Diagnostic Strategies in Chronic Disorders of Consciousness: An Overview on the (Re-)Emergent Role of Neurophysiology

by Luana Billeri, Serena Filoni, Emanuele Francesco Russo, Simona Portaro, David Militi, Rocco Salvatore Calabrò and Antonino Naro

Brain Sci. 2020, 10(1), 42; https://doi.org/10.3390/brainsci10010042 - 10 Jan 2020

Cited by 10 | Viewed by 3709

Abstract

The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including [...] Read more.

The differential diagnosis of patients with Disorder of Consciousness (DoC), in particular in the chronic phase, is significantly difficult. Actually, about 40% of patients with unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS) are misdiagnosed. Indeed, only advanced paraclinical approaches, including advanced EEG analyses, can allow achieving a more reliable diagnosis, that is, discovering residual traces of awareness in patients with UWS (namely, functional Locked-In Syndrome (fLIS)). These approaches aim at capturing the residual brain network models, at rest or that may be activated in response to relevant stimuli, which may be appropriate for awareness to emerge (despite their insufficiency to generate purposeful motor behaviors). For this, different brain network models have been studied in patients with DoC by using sensory stimuli (i.e., passive tasks), probing response to commands (i.e., active tasks), and during resting-state. Since it can be difficult for patients with DoC to perform even simple active tasks, this scoping review aims at summarizing the current, innovative neurophysiological examination methods in resting state/passive modality to differentiate and prognosticate patients with DoC. We conclude that the electrophysiologically-based diagnostic procedures represent an important resource for diagnosis, prognosis, and, therefore, management of patients with DoC, using advance passive and resting state paradigm analyses for the patients who lie in the “greyzones” between MCS, UWS, and fLIS. Full article

(This article belongs to the Special Issue Advances in Disorders of Consciousness)

11 pages, 2509 KiB

Open AccessPerspective

Insights from a Bibliometric Analysis of Vividness and Its Links with Consciousness and Mental Imagery

by Stefanie Haustein, André Vellino and Amedeo D’Angiulli

Brain Sci. 2020, 10(1), 41; https://doi.org/10.3390/brainsci10010041 - 10 Jan 2020

Cited by 6 | Viewed by 3962

Abstract

We performed a bibliometric analysis of the peer-reviewed literature on vividness between 1900 and 2019 indexed by the Web of Science and compared it with the same analysis of publications on consciousness and mental imagery. While we observed a similarity between the citation [...] Read more.

We performed a bibliometric analysis of the peer-reviewed literature on vividness between 1900 and 2019 indexed by the Web of Science and compared it with the same analysis of publications on consciousness and mental imagery. While we observed a similarity between the citation growth rates for publications about each of these three subjects, our analysis shows that these concepts rarely overlap (co-occur) in the literature, revealing a surprising paucity of research about these concepts taken together. A disciplinary analysis shows that the field of Psychology dominates the topic of vividness, even though the total number of publications containing that term is small and the concept occurs in several other disciplines such as Computer Science and Artificial Intelligence. The present findings suggest that without a coherent unitary framework for the use of vividness in research, important opportunities for advancing the field might be missed. In contrast, we suggest that an evidence-based framework (such as the bibliometric analytic methods as exemplified here) will help to guide research from all disciplines that are concerned with vividness and help to resolve the challenge of epistemic incommensurability amongst published research in multidisciplinary fields. Full article

(This article belongs to the Special Issue Vividness, Consciousness, and Mental Imagery: Making the Missing Links across Disciplines and Methods)

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14 pages, 8692 KiB

Open AccessArticle

The Effect of Aging on the ERP Correlates of Feedback Processing in the Probabilistic Selection Task

by Robert West and AnnMarie Huet

Brain Sci. 2020, 10(1), 40; https://doi.org/10.3390/brainsci10010040 - 9 Jan 2020

Cited by 5 | Viewed by 3376

Abstract

Feedback processing contributes to efficient learning, decision making, and social interaction. Studies using event-related brain potentials (ERPs) reveal that feedback processing is associated with transient ERP components over the medial frontal and posterior regions of the scalp that distinguish between positive and negative [...] Read more.

Feedback processing contributes to efficient learning, decision making, and social interaction. Studies using event-related brain potentials (ERPs) reveal that feedback processing is associated with transient ERP components over the medial frontal and posterior regions of the scalp that distinguish between positive and negative feedback. There is some evidence indicating that aging has differential effects on the ERP correlates of feedback processing in a gambling task, and the current study was designed to extend these findings to a reinforcement learning paradigm. Younger and older adults performed the probabilistic selection task while ERPs elicited by feedback cues indicating a correct or incorrect choice were recorded during the learning phase. The ERPs revealed that the amplitude of the feedback negativity and frontal P3 were attenuated in older adults relative to younger adults. The amplitude of a temporal positivity was also attenuated in older adults; in contrast, the amplitude of an occipital negativity was insensitive to the effects of aging. These findings indicate that aging may be associated with the disruption of both local activity and long-range connectivity between neural structures related to feedback processing. Full article

(This article belongs to the Special Issue Collection on Cognitive Neuroscience)

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26 pages, 2549 KiB

Open AccessArticle

Infants Segment Words from Songs—An EEG Study

by Tineke M. Snijders, Titia Benders and Paula Fikkert

Brain Sci. 2020, 10(1), 39; https://doi.org/10.3390/brainsci10010039 - 9 Jan 2020

Cited by 11 | Viewed by 6570

Abstract

Children’s songs are omnipresent and highly attractive stimuli in infants’ input. Previous work suggests that infants process linguistic–phonetic information from simplified sung melodies. The present study investigated whether infants learn words from ecologically valid children’s songs. Testing 40 Dutch-learning 10-month-olds in a familiarization-then-test [...] Read more.

Children’s songs are omnipresent and highly attractive stimuli in infants’ input. Previous work suggests that infants process linguistic–phonetic information from simplified sung melodies. The present study investigated whether infants learn words from ecologically valid children’s songs. Testing 40 Dutch-learning 10-month-olds in a familiarization-then-test electroencephalography (EEG) paradigm, this study asked whether infants can segment repeated target words embedded in songs during familiarization and subsequently recognize those words in continuous speech in the test phase. To replicate previous speech work and compare segmentation across modalities, infants participated in both song and speech sessions. Results showed a positive event-related potential (ERP) familiarity effect to the final compared to the first target occurrences during both song and speech familiarization. No evidence was found for word recognition in the test phase following either song or speech. Comparisons across the stimuli of the present and a comparable previous study suggested that acoustic prominence and speech rate may have contributed to the polarity of the ERP familiarity effect and its absence in the test phase. Overall, the present study provides evidence that 10-month-old infants can segment words embedded in songs, and it raises questions about the acoustic and other factors that enable or hinder infant word segmentation from songs and speech. Full article

(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)

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19 pages, 3441 KiB

Open AccessArticle

Early Attentional Modulation by Working Memory Training in Young Adult ADHD Patients during a Risky Decision-Making Task

by Manon E. Jaquerod, Sarah K. Mesrobian, Alessandro E. P. Villa, Michel Bader and Alessandra Lintas

Brain Sci. 2020, 10(1), 38; https://doi.org/10.3390/brainsci10010038 - 9 Jan 2020

Cited by 7 | Viewed by 4897

Abstract

Background: Working memory (WM) deficits and impaired decision making are among the characteristic symptoms of patients affected by attention deficit/hyperactivity disorder (ADHD). The inattention associated with the disorder is likely to be due to functional deficits of the neural networks inhibiting irrelevant [...] Read more.

Background: Working memory (WM) deficits and impaired decision making are among the characteristic symptoms of patients affected by attention deficit/hyperactivity disorder (ADHD). The inattention associated with the disorder is likely to be due to functional deficits of the neural networks inhibiting irrelevant sensory input. In the presence of unnecessary information, a good decisional process is impaired and ADHD patients tend to take risky decisions. This study is aimed to test the hypothesis that the level of difficulty of a WM training (WMT) is affecting the top-down modulation of the attentional processes in a probabilistic gambling task. Methods: Event-related potentials (ERP) triggered by the choice of the amount wagered in the gambling task were recorded, before and after WMT with a the dual n-back task, in young ADHD adults and matched controls. For each group of participants, randomly assigned individuals were requested to perform WMT with a fixed baseline level of difficulty. The remaining participants were trained with a performance-dependent adaptive n-level of difficulty. Results: We compared the ERP recordings before and after 20 days of WMT in each subgroup. The analysis was focused on the time windows with at least three recording sites showing differences before and after training, after Bonferroni correction (

p < 0.05

). In ADHD, the P1 wave component was selectively affected at frontal sites and its shape was recovered close to controls’ only after adaptive training. In controls, the strongest contrast was observed at parietal level with a left hemispheric dominance at latencies near 900 ms, more after baseline than after adaptive training. Conclusion: Partial restoration of early selective attentional processes in ADHD patients might occur after WMT with a high cognitive load. Modified frontal sites’ activities might constitute a neural marker of this effect in a gambling task. In controls, conversely, an increase in late parietal negativity might rather be a marker of an increase in transfer effects to fluid intelligence. Full article

(This article belongs to the Special Issue ERP and EEG Markers of Brain Visual Attentional Processing)

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8 pages, 2047 KiB

Open AccessCommunication

Cortical Resonance to Visible and Invisible Visual Rhythms

by Claudio de’Sperati

Brain Sci. 2020, 10(1), 37; https://doi.org/10.3390/brainsci10010037 - 9 Jan 2020

Cited by 5 | Viewed by 3836

Abstract

Humans are rather poor in judging the right speed of video scenes. For example, a soccer match may be sped up so as to last only 80 min without observers noticing it. However, both adults and children seem to have a systematic, though [...] Read more.

Humans are rather poor in judging the right speed of video scenes. For example, a soccer match may be sped up so as to last only 80 min without observers noticing it. However, both adults and children seem to have a systematic, though often biased, notion of what should be the right speed of a given video scene. We therefore explored cortical responsiveness to video speed manipulations in search of possible differences between explicit and implicit speed processing. We applied sinusoidal speed modulations to a video clip depicting a naturalistic scene as well as a traditional laboratory visual stimulus (random dot kinematogram, RDK), and measured both perceptual sensitivity and cortical responses (steady-state visual evoked potentials, SSVEPs) to speed modulations. In five observers, we found a clear perceptual sensitivity increase and a moderate SSVEP amplitude increase with increasing speed modulation strength. Cortical responses were also found with weak, undetected speed modulations. These preliminary findings suggest that the cortex responds globally to periodic video speed modulations, even when observers do not notice them. This entrainment mechanism may be the basis of automatic resonance to the rhythms of the external world. Full article

(This article belongs to the Special Issue ERP and EEG Markers of Brain Visual Attentional Processing)

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18 pages, 1788 KiB

Open AccessArticle

How the Brain Understands Spoken and Sung Sentences

by Sonja Rossi, Manfred F. Gugler, Markus Rungger, Oliver Galvan, Patrick G. Zorowka and Josef Seebacher

Brain Sci. 2020, 10(1), 36; https://doi.org/10.3390/brainsci10010036 - 8 Jan 2020

Cited by 9 | Viewed by 5352

Abstract

The present study investigates whether meaning is similarly extracted from spoken and sung sentences. For this purpose, subjects listened to semantically correct and incorrect sentences while performing a correctness judgement task. In order to examine underlying neural mechanisms, a multi-methodological approach was chosen [...] Read more.

The present study investigates whether meaning is similarly extracted from spoken and sung sentences. For this purpose, subjects listened to semantically correct and incorrect sentences while performing a correctness judgement task. In order to examine underlying neural mechanisms, a multi-methodological approach was chosen combining two neuroscientific methods with behavioral data. In particular, fast dynamic changes reflected in the semantically associated N400 component of the electroencephalography (EEG) were simultaneously assessed with the topographically more fine-grained vascular signals acquired by the functional near-infrared spectroscopy (fNIRS). EEG results revealed a larger N400 for incorrect compared to correct sentences in both spoken and sung sentences. However, the N400 was delayed for sung sentences, potentially due to the longer sentence duration. fNIRS results revealed larger activations for spoken compared to sung sentences irrespective of semantic correctness at predominantly left-hemispheric areas, potentially suggesting a greater familiarity with spoken material. Furthermore, the fNIRS revealed a widespread activation for correct compared to incorrect sentences irrespective of modality, potentially indicating a successful processing of sentence meaning. The combined results indicate similar semantic processing in speech and song. Full article

(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)

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22 pages, 6618 KiB

Open AccessArticle

Expression and Localization of Kv1.1 and Kv3.1b Potassium Channels in the Cochlear Nucleus and Inferior Colliculus after Long-Term Auditory Deafferentation

by Clara M. Poveda, Maria L. Valero, Marianny Pernia, Juan C. Alvarado, David K. Ryugo, Miguel A. Merchan and Jose M. Juiz

Brain Sci. 2020, 10(1), 35; https://doi.org/10.3390/brainsci10010035 - 8 Jan 2020

Cited by 7 | Viewed by 3948

Abstract

Deafness affects the expression and distribution of voltage-dependent potassium channels (Kvs) of central auditory neurons in the short-term, i.e., hours to days, but the consequences in the expression of Kvs after long-term deafness remain unknown. We tested expression and distribution of Kv1.1 and [...] Read more.

Deafness affects the expression and distribution of voltage-dependent potassium channels (Kvs) of central auditory neurons in the short-term, i.e., hours to days, but the consequences in the expression of Kvs after long-term deafness remain unknown. We tested expression and distribution of Kv1.1 and Kv3.1b, key for auditory processing, in the rat cochlear nucleus (CN), and in the inferior colliculus (IC), at 1, 15 and 90 days after mechanical lesion of the cochlea, using a combination of qRT-PCR and Western blot in the whole CN, along with semi-quantitative immunocytochemistry in the AVCN, where the role of both Kvs in the control of excitability for accurate auditory timing signal processing is well established. Neither Kv1.1/Kv3.1b mRNA or protein expression changed significantly in the CN between 1 and 15 days after deafness. At 90 days post-lesion, however, mRNA and protein expression for both Kvs increased, suggesting that regulation of Kv1.1 and Kv3.1b expression is part of cellular mechanisms for long-term adaptation to auditory deprivation in the CN. Consistent with these findings, immunocytochemistry showed increased labeling intensity for both Kvs in the AVCN at day 90 after cochlear lesion. This increase argues that up-regulation of Kv1.1 and Kv3.1b in AVCN neurons may be required to adapt intrinsic excitability to altered input over the long term after auditory deprivation. Contrary to these findings in the CN, expression levels of Kv1.1 and Kv3.1b in the IC did not undergo major changes after cochlear lesion. In particular, there was no evidence of long-term up-regulation of either Kv1.1 or Kv3.1b, supporting that such post-lesion adaptive mechanism may not be needed in the IC. These results reveal that post-lesion adaptations do not necessarily involve stereotyped plastic mechanisms along the entire auditory pathway. Full article

(This article belongs to the Special Issue Central Auditory Plasticity)

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10 pages, 379 KiB

Open AccessArticle

Perspectives on Deep Brain Stimulation and Its Earlier Use for Parkinson’s Disease: A Qualitative Study of US Patients

by Laura Y. Cabrera, Karen Kelly-Blake and Christos Sidiropoulos

Brain Sci. 2020, 10(1), 34; https://doi.org/10.3390/brainsci10010034 - 8 Jan 2020

Cited by 13 | Viewed by 4123

Abstract

Background: Deep brain stimulation (DBS) is being used earlier than was previously the case in the disease progression in people with Parkinson’s disease (PD). To explore preferences about the timing of DBS, we asked PD patients with DBS whether they would have preferred [...] Read more.

Background: Deep brain stimulation (DBS) is being used earlier than was previously the case in the disease progression in people with Parkinson’s disease (PD). To explore preferences about the timing of DBS, we asked PD patients with DBS whether they would have preferred the implantation procedure to have occurred earlier after diagnosis. Methods: Twenty Michigan-based patients were interviewed about both their experiences with DBS as well as their attitudes regarding the possible earlier use of DBS. We used a structured interview, with both closed and open-ended questions. Interviews were transcribed verbatim and analyzed using a mixed-methods approach. Results: We found that the majority of our participants (72%) had high overall satisfaction with DBS in addressing motor symptoms (mean of 7.5/10) and quality of life (mean of 8.25/10). Participants were mixed about whether they would have undergone DBS earlier than they did, with five participants being unsure and the remaining nearly equally divided between yes and no. Conclusion: Patient attitudes on the early use of DBS were mixed. Our results suggest that while patients were grateful for improvements experienced with DBS, they would not necessarily have endorsed its implementation earlier in their disease progression. Larger studies are needed to further examine our findings. Full article

(This article belongs to the Special Issue Brain Stimulation and Parkinson's Disease)

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16 pages, 1830 KiB

Open AccessArticle

Neuromuscular Mechanisms Underlying Changes in Force Production during an Attentional Focus Task

by Shawn Wiseman, Shahab Alizadeh, Israel Halperin, Behzad Lahouti, Nicholas J. Snow, Kevin E. Power and Duane C. Button

Brain Sci. 2020, 10(1), 33; https://doi.org/10.3390/brainsci10010033 - 7 Jan 2020

Cited by 9 | Viewed by 5215

Abstract

We examined the effects of attentional focus cues on maximal voluntary force output of the elbow flexors and the underlying physiological mechanisms. Eleven males participated in two randomized experimental sessions. In each session, four randomized blocks of three maximal voluntary contractions (MVC) were [...] Read more.

We examined the effects of attentional focus cues on maximal voluntary force output of the elbow flexors and the underlying physiological mechanisms. Eleven males participated in two randomized experimental sessions. In each session, four randomized blocks of three maximal voluntary contractions (MVC) were performed. The blocks consisted of two externally and two internally attentional focus cued blocks. In one of the sessions, corticospinal excitability (CSE) was measured. During the stimulation session transcranial magnetic, transmastoid and Erb’s point stimulations were used to induce motor evoked potentials (MEPs), cervicomedullary MEP (CMEPs) and maximal muscle action potential (Mmax), respectively in the biceps brachii. Across both sessions forces were lower (p = 0.024) under the internal (282.4 ± 60.3 N) compared to the external condition (310.7 ± 11.3 N). Muscle co-activation was greater (p = 0.016) under the internal (26.3 ± 11.5%) compared with the external condition (21.5 ± 9.4%). There was no change in CSE. Across both sessions, force measurements were lower (p = 0.033) during the stimulation (279.0 ± 47.1 N) compared with the no-stimulation session (314.1 ± 57.5 N). In conclusion, external focus increased force, likely due to reduced co-activation. Stimulating the corticospinal pathway may confound attentional focus. The stimulations may distract participants from the cues and/or disrupt areas of the cortex responsible for attention and focus. Full article

(This article belongs to the Special Issue Acute and Chronic Changes in Neural Excitability During Physical Activity in Non-Pathological States)

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10 pages, 11376 KiB

Open AccessArticle

Inhibitory Effects of Myricetin on Lipopolysaccharide-Induced Neuroinflammation

by Jung-Hee Jang, Seung Hoon Lee, Kyungsook Jung, Horyong Yoo and Gunhyuk Park

Brain Sci. 2020, 10(1), 32; https://doi.org/10.3390/brainsci10010032 - 6 Jan 2020

Cited by 35 | Viewed by 4969

Abstract

Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. [...] Read more.

Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. However, whether myricetin inhibits lipopolysaccharide (LPS)-induced neuroinflammation in hippocampus and cortex regions is not known. To test this, we examined the effects of myricetin on LPS-induced neuroinflammation in a microglial BV2 cell line. We found that myricetin significantly downregulated several markers of the neuroinflammatory response in LPS-induced activated microglia, including inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory modulators and cytokines such as prostaglandin E2 (PGE₂), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Moreover, myricetin suppressed the expression of c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, myricetin inhibited LPS-induced macrophages and microglial activation in the hippocampus and cortex of mice. Based on our results, we suggest that myricetin inhibits neuroinflammation in BV2 microglia by inhibiting the MAPK signaling pathway and the production of proinflammatory modulators and cytokines. Therefore, this could potentially be used for the treatment of neuroinflammatory diseases. Full article

(This article belongs to the Section Neuroglia)

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12 pages, 1459 KiB

Open AccessArticle

Differential Expression of CD31 and Von Willebrand Factor on Endothelial Cells in Different Regions of the Human Brain: Potential Implications for Cerebral Malaria Pathogenesis

by Smart Ikechukwu Mbagwu and Luis Filgueira

Brain Sci. 2020, 10(1), 31; https://doi.org/10.3390/brainsci10010031 - 6 Jan 2020

Cited by 16 | Viewed by 5900

Abstract

Cerebral microvascular endothelial cells (CMVECs) line the vascular system of the brain and are the chief cells in the formation and function of the blood brain barrier (BBB). These cells are heterogeneous along the cerebral vasculature and any dysfunctional state in these cells [...] Read more.

Cerebral microvascular endothelial cells (CMVECs) line the vascular system of the brain and are the chief cells in the formation and function of the blood brain barrier (BBB). These cells are heterogeneous along the cerebral vasculature and any dysfunctional state in these cells can result in a local loss of function of the BBB in any region of the brain. There is currently no report on the distribution and variation of the CMVECs in different brain regions in humans. This study investigated microcirculation in the adult human brain by the characterization of the expression pattern of brain endothelial cell markers in different brain regions. Five different brain regions consisting of the visual cortex, the hippocampus, the precentral gyrus, the postcentral gyrus, and the rhinal cortex obtained from three normal adult human brain specimens were studied and analyzed for the expression of the endothelial cell markers: cluster of differentiation 31 (CD31) and von-Willebrand-Factor (vWF) through immunohistochemistry. We observed differences in the expression pattern of CD31 and vWF between the gray matter and the white matter in the brain regions. Furthermore, there were also regional variations in the pattern of expression of the endothelial cell biomarkers. Thus, this suggests differences in the nature of vascularization in various regions of the human brain. These observations also suggest the existence of variation in structure and function of different brain regions, which could reflect in the pathophysiological outcomes in a diseased state. Full article

(This article belongs to the Special Issue Advances in Cerebral Blood Flow Regulation and Neurovascular Dysfunction)

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16 pages, 1918 KiB

Open AccessFeature PaperReview

Calcitonin Gene-Related Peptide (CGRP) and Cluster Headache

by Andrea Carmine Belin, Caroline Ran and Lars Edvinsson

Brain Sci. 2020, 10(1), 30; https://doi.org/10.3390/brainsci10010030 - 6 Jan 2020

Cited by 42 | Viewed by 12230

Abstract

Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP [...] Read more.

Cluster headache (CH) is a severe primary headache with a prevalence of 1/1000 individuals, and a predominance in men. Calcitonin gene-related peptide (CGRP) is a potent vasodilator, originating in trigeminal neurons and has a central role in CH pathophysiology. CGRP and the CGRP receptor complex have recently taken center stage as therapeutic targets for primary headaches, such as migraine. Multiple CGRP and CGRP receptor monoclonal antibodies, as well as small molecule antagonists (gepants) are on their way constituting a new frontier of migraine and possibly CH medication. During a CH attack, there is an activation of the trigeminal-autonomic reflex with the release of CGRP, and inversely if CGRP is administered to a CH patient in an active disease phase, it triggers an attack. Increased levels of CGRP have been found in ipsilateral jugular vein blood during the active phase of CH. This process is hypothesized to have a key role in the intense pain perception and in the associated distinctive vasodilation. So far, clinical tests of CGRP antibodies have been inconclusive in CH patients. This review summarizes the current state of knowledge on the role of CGRP in CH pathology, and as a target for future treatments. Full article

(This article belongs to the Special Issue Recent Advances and New Insights in Cluster Headache)

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14 pages, 1997 KiB

Open AccessArticle

The Use of Hyperscanning to Investigate the Role of Social, Affective, and Informative Gestures in Non-Verbal Communication. Electrophysiological (EEG) and Inter-Brain Connectivity Evidence

by Michela Balconi and Giulia Fronda

Brain Sci. 2020, 10(1), 29; https://doi.org/10.3390/brainsci10010029 - 5 Jan 2020

Cited by 27 | Viewed by 6236

Abstract

Communication can be considered as a joint action that involves two or more individuals transmitting different information. In particular, non-verbal communication involves body movements used to communicate different information, characterized by the use of specific gestures. The present study aims to investigate the [...] Read more.

Communication can be considered as a joint action that involves two or more individuals transmitting different information. In particular, non-verbal communication involves body movements used to communicate different information, characterized by the use of specific gestures. The present study aims to investigate the electrophysiological (EEG) correlates underlying the use of affective, social, and informative gestures during a non-verbal interaction between an encoder and decoder. From the results of the single brain and inter-brain analyses, an increase of frontal alpha, delta, and theta brain responsiveness and inter-brain connectivity emerged for affective and social gestures; while, for informative gestures, an increase of parietal alpha brain responsiveness and alpha, delta, and theta inter-brain connectivity was observed. Regarding the inter-agents’ role, an increase of frontal alpha activity was observed in the encoder compared to the decoder for social and affective gestures. Finally, regarding gesture valence, an increase of theta brain responsiveness and theta and beta inter-brain connectivity was observed for positive gestures on the left side compared to the right one. This study, therefore, revealed the function of the gesture type and valence in influencing individuals’ brain responsiveness and inter-brain connectivity, showing the presence of resonance mechanisms underlying gesture execution and observation. Full article

(This article belongs to the Special Issue Collection on Cognitive Neuroscience)

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25 pages, 1800 KiB

Open AccessReview

Identifying Core Regions for Path Integration on Medial Entorhinal Cortex of Hippocampal Formation

by Ayako Fukawa, Takahiro Aizawa, Hiroshi Yamakawa and Ikuko Eguchi Yairi

Brain Sci. 2020, 10(1), 28; https://doi.org/10.3390/brainsci10010028 - 5 Jan 2020

Cited by 12 | Viewed by 5948

Abstract

Path integration is one of the functions that support the self-localization ability of animals. Path integration outputs position information after an animal’s movement when initial-position and movement information is input. The core region responsible for this function has been identified as the medial [...] Read more.

Path integration is one of the functions that support the self-localization ability of animals. Path integration outputs position information after an animal’s movement when initial-position and movement information is input. The core region responsible for this function has been identified as the medial entorhinal cortex (MEC), which is part of the hippocampal formation that constitutes the limbic system. However, a more specific core region has not yet been identified. This research aims to clarify the detailed structure at the cell-firing level in the core region responsible for path integration from fragmentarily accumulated experimental and theoretical findings by reviewing 77 papers. This research draws a novel diagram that describes the MEC, the hippocampus, and their surrounding regions by focusing on the MEC’s input/output (I/O) information. The diagram was created by summarizing the results of exhaustively scrutinizing the papers that are relative to the I/O relationship, the connection relationship, and cell position and firing pattern. From additional investigations, we show function information related to path integration, such as I/O information and the relationship between multiple functions. Furthermore, we constructed an algorithmic hypothesis on I/O information and path-integration calculation method from the diagram and the information of functions related to path integration. The algorithmic hypothesis is composed of regions related to path integration, the I/O relations between them, the calculation performed there, and the information representations (cell-firing pattern) in them. Results of examining the hypothesis confirmed that the core region responsible for path integration was either stellate cells in layer II or pyramidal cells in layer III of the MEC. Full article

(This article belongs to the Section Computational Neuroscience and Neuroinformatics)

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