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Brain Sci., Volume 8, Issue 1 (January 2018) – 19 articles

Cover Story (view full-size image): The cover image shows the viability and cell death of cerebellar granule neurons (CGN) (cyan arrow) and astrocytes (red arrow) treated with cerebrospinal fluid (CSF) of Multiple Sclerosis (MS) patients. The CSF of MS patients contain some factors that may have caused selective cell death in CGN. We discuss that those factors may induce cell death by downregulated expression of genes involved in glucose metabolism and ATP production in these CSF-treated neurons. The CSF effect differs according to MS severity; it is higher in relapsing MS with oligoclonal IgG and IgM bands (G+/M+ RMS) and spinal MS, which may be related to their differential restoration capacity of neuronal damage between MS subtypes of patients.View the paper here.
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15 pages, 644 KiB  
Review
Deep Brain Stimulation—Possible Treatment Strategy for Pathologically Altered Body Weight?
by Philip Prinz and Andreas Stengel
Brain Sci. 2018, 8(1), 19; https://doi.org/10.3390/brainsci8010019 - 22 Jan 2018
Cited by 8 | Viewed by 6296
Abstract
The treatment of obesity and eating disorders such as binge-eating disorder or anorexia nervosa is challenging. Besides lifestyle changes and pharmacological options, bariatric surgery represents a well-established and effective-albeit invasive-treatment of obesity, whereas for binge-eating disorder and anorexia nervosa mostly psychotherapy options exist. [...] Read more.
The treatment of obesity and eating disorders such as binge-eating disorder or anorexia nervosa is challenging. Besides lifestyle changes and pharmacological options, bariatric surgery represents a well-established and effective-albeit invasive-treatment of obesity, whereas for binge-eating disorder and anorexia nervosa mostly psychotherapy options exist. Deep brain stimulation (DBS), a method that influences the neuronal network, is by now known for its safe and effective applicability in patients with Parkinson’s disease. However, the use does not seem to be restricted to these patients. Recent preclinical and first clinical evidence points towards the use of DBS in patients with obesity and eating disorders as well. Depending on the targeted area in the brain, DBS can either inhibit food intake and body weight or stimulate energy intake and subsequently body weight. The current review focuses on preclinical and clinical evidence of DBS to modulate food intake and body weight and highlight the different brain areas targeted, stimulation protocols applied and downstream signaling modulated. Lastly, this review will also critically discuss potential safety issues and gaps in knowledge to promote further studies. Full article
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5 pages, 187 KiB  
Review
DBS in Treatment of Post-Traumatic Stress Disorder
by Angelo Lavano, Giusy Guzzi, Attilio Della Torre, Serena Marianna Lavano, Raffaele Tiriolo and Giorgio Volpentesta
Brain Sci. 2018, 8(1), 18; https://doi.org/10.3390/brainsci8010018 - 20 Jan 2018
Cited by 15 | Viewed by 5242
Abstract
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested and deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. We review the neurocircuitry and up-to-date clinical [...] Read more.
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested and deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. We review the neurocircuitry and up-to-date clinical concepts which are behind the use of DBS in posttraumatic stress disorder (PTSD). The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. DBS for PTSD is in its preliminary phases and likely to provide hope for patients with medical refractory PTSD following the results of randomized controlled studies. Full article
10 pages, 197 KiB  
Review
Awake versus Asleep Deep Brain Stimulation Surgery: Technical Considerations and Critical Review of the Literature
by Ryan B. Kochanski and Sepehr Sani
Brain Sci. 2018, 8(1), 17; https://doi.org/10.3390/brainsci8010017 - 19 Jan 2018
Cited by 40 | Viewed by 5695
Abstract
Advancements in neuroimaging have led to a trend toward direct, image-based targeting under general anesthesia without the use of microelectrode recording (MER) or intraoperative test stimulation, also referred to as “asleep” deep brain stimulation (DBS) surgery. Asleep DBS, utilizing imaging in the form [...] Read more.
Advancements in neuroimaging have led to a trend toward direct, image-based targeting under general anesthesia without the use of microelectrode recording (MER) or intraoperative test stimulation, also referred to as “asleep” deep brain stimulation (DBS) surgery. Asleep DBS, utilizing imaging in the form of intraoperative computed tomography (iCT) or magnetic resonance imaging (iMRI), has demonstrated reliable targeting accuracy of DBS leads implanted within the globus pallidus and subthalamic nucleus while also improving clinical outcomes in patients with Parkinson’s disease. In lieu, of randomized control trials, retrospective comparisons between asleep and awake DBS with MER have shown similar short-term efficacy with the potential for decreased complications in asleep cohorts. In lieu of long-term outcome data, awake DBS using MER must demonstrate more durable outcomes with fewer stimulation-induced side effects and lead revisions in order for its use to remain justifiable; although patient-specific factors may also be used to guide the decision regarding which technique may be most appropriate and tolerable to the patient. Full article
19 pages, 1034 KiB  
Article
Depression Symptom Patterns and Social Correlates among Chinese Americans
by Lin Zhu
Brain Sci. 2018, 8(1), 16; https://doi.org/10.3390/brainsci8010016 - 16 Jan 2018
Cited by 8 | Viewed by 4467
Abstract
The aim of this study is to examine and compare the depression symptoms pattern and social correlates in three groups: foreign-born Chinese Americans, US-born Chinese Americans, and non-Hispanic whites. This study used data from the Collaborative Psychiatric Epidemiology Surveys (CPES). The study sample [...] Read more.
The aim of this study is to examine and compare the depression symptoms pattern and social correlates in three groups: foreign-born Chinese Americans, US-born Chinese Americans, and non-Hispanic whites. This study used data from the Collaborative Psychiatric Epidemiology Surveys (CPES). The study sample consists of 599 Chinese Americans (468 for the foreign-born and 121 for the US-born) and 4032 non-Hispanic whites. Factor analysis was used to examine the depression symptom patterns by each subgroup. Four depression symptoms dimensions were examined: negative affect, somatic symptoms, cognitive symptoms, and suicidality. Logistic regression was used to investigate the effects of sociodemographic (age, gender, marital status, and education), physical health condition, and social relational factors (supports from and conflict with family and friends) on specific types of depression symptoms separately for the three subgroups. The findings showed little differences in depression symptom patterns but clear variation in the social correlates to the four depression dimensions across the three ethnocultural groups, foreign-born Chinese Americans, US-born Chinese Americans, and non-Hispanic whites. Clinicians should take into account the sociocultural factors of patients when making diagnosis and suggesting treatments. In addition, psychiatrists, psychologists, or other mental health service providers should offer treatment and coping suggestions based on the specific symptom dimensions of patients, and patients’ ethnocultural backgrounds. Full article
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13 pages, 245 KiB  
Review
Glioblastoma under Siege: An Overview of Current Therapeutic Strategies
by Mayra Paolillo, Cinzia Boselli and Sergio Schinelli
Brain Sci. 2018, 8(1), 15; https://doi.org/10.3390/brainsci8010015 - 16 Jan 2018
Cited by 89 | Viewed by 8275
Abstract
Glioblastoma is known to be one of the most lethal and untreatable human tumors. Surgery and radiotherapy in combination with classical alkylating agents such as temozolomide offer little hope to escape a poor prognosis. For these reasons, enormous efforts are currently devoted to [...] Read more.
Glioblastoma is known to be one of the most lethal and untreatable human tumors. Surgery and radiotherapy in combination with classical alkylating agents such as temozolomide offer little hope to escape a poor prognosis. For these reasons, enormous efforts are currently devoted to refine in vivo and in vitro models with the specific goal of finding new molecular aberrant pathways, suitable to be targeted by a variety of therapeutic approaches, including novel pharmaceutical formulations and immunotherapy strategies. In this review, we will first discuss current molecular classification based on genomic and transcriptomic criteria. Also, the state of the art in current clinical practice for glioblastoma therapy in the light of the recent molecular classification, together with ongoing phases II and III clinical trials, will be described. Finally, new pharmaceutical formulations such as nanoparticles and viral vectors, together with new strategies entailing the use of monoclonal antibodies, vaccines and immunotherapy agents, such as checkpoint inhibitors, will also be discussed. Full article
(This article belongs to the Special Issue Advances in Adult and Pediatric Brain Tumor Management)
7 pages, 6940 KiB  
Case Report
Blood Flow and Continuous EEG Changes during Symptomatic Plateau Waves
by Natalie Kreitzer, Maggie Huynh and Brandon Foreman
Brain Sci. 2018, 8(1), 14; https://doi.org/10.3390/brainsci8010014 - 12 Jan 2018
Cited by 4 | Viewed by 4886
Abstract
Benign meningiomas uncommonly lead to significant cerebral edema, with only a few cases previously reported in the medical literature. The present study describes the case of a 49-year-old female who had a meningioma resection. She subsequently developed malignant cerebral edema and had episodes [...] Read more.
Benign meningiomas uncommonly lead to significant cerebral edema, with only a few cases previously reported in the medical literature. The present study describes the case of a 49-year-old female who had a meningioma resection. She subsequently developed malignant cerebral edema and had episodes that were initially concerning for seizure activity. However, transient blood flow changes concerning for intracranial pressure (ICP) crises, were demonstrated on electroencephalogram (EEG) as well as noninvasive cerebral blood flow monitoring. The present case highlights the importance of close monitoring in patients with post meningioma resection cerebral edema because of the possibility of ICP crises. Full article
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6 pages, 209 KiB  
Editorial
Acknowledgement to Reviewers of Brain Sciences in 2017
by Brain Sciences Editorial Office
Brain Sci. 2018, 8(1), 13; https://doi.org/10.3390/brainsci8010013 - 10 Jan 2018
Viewed by 3667
Abstract
Peer review is an essential part in the publication process, ensuring that Brain Sciences maintains high quality standards for its published papers.[...] Full article
8 pages, 878 KiB  
Case Report
Recurrent Hemorrhagic Conversion of Ischemic Stroke in a Patient with Mechanical Heart Valve: A Case Report and Literature Review
by Micheal Jace Tarver, Tyler Schmidt and Michael T. Koltz
Brain Sci. 2018, 8(1), 12; https://doi.org/10.3390/brainsci8010012 - 07 Jan 2018
Cited by 2 | Viewed by 6126
Abstract
The authors present a unique case of recurrent stroke, discovered to be secondary to hemorrhagic conversion of microemboli from a mechanical aortic valve despite anticoagulation with Coumadin. The complexity of this case was magnified by the patient’s young age, a mechanical heart valve [...] Read more.
The authors present a unique case of recurrent stroke, discovered to be secondary to hemorrhagic conversion of microemboli from a mechanical aortic valve despite anticoagulation with Coumadin. The complexity of this case was magnified by the patient’s young age, a mechanical heart valve (MHV), and a need for anticoagulation to maintain MHV patency in a setting of potentially life-threatening intracranial hemorrhage. Anticoagulant and antiplatelet therapy are risk factors for hemorrhagic conversion post-cerebral ischemia; however, the pathophysiology underlying endothelial cell dysfunction causing red blood cell extravasation is an active area of basic and clinical research. The need for randomized clinical trials to aid in the creation of standardized treatment protocol continues to go unmet. Consequently, there is marked variation in therapeutic approaches to treating intracranial hemorrhage in patients with an MHV. Unfortunately, patients with an MHV are considered at high thromboembolic (TE) risk, and these patients are often excluded from clinical trials of acute stroke due to their increased TE potential. The authors feel this case represents an example of endothelial dysfunction secondary to microthrombotic events originating from an MHV, which caused ischemic stroke with hemorrhagic conversion complicated by the need for anticoagulation for an MHV. This case offers a definitive treatment algorithm for a complex clinical dilemma. Full article
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11 pages, 2235 KiB  
Article
Neurodegeneration and Sensorimotor Deficits in the Mouse Model of Traumatic Brain Injury
by Saurav Bhowmick, Veera D‘Mello, Nizmi Ponery and P. M. Abdul-Muneer
Brain Sci. 2018, 8(1), 11; https://doi.org/10.3390/brainsci8010011 - 06 Jan 2018
Cited by 30 | Viewed by 6858
Abstract
Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces [...] Read more.
Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and poly (ADP-ribose) polymerase (PARP) and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, the inverted screen test, and the climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI. Full article
(This article belongs to the Special Issue Novel Mechanisms and Strategies for Neural Repair)
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14 pages, 884 KiB  
Review
Effects of Early Neglect Experience on Recognition and Processing of Facial Expressions: A Systematic Review
by Victoria Doretto and Sandra Scivoletto
Brain Sci. 2018, 8(1), 10; https://doi.org/10.3390/brainsci8010010 - 06 Jan 2018
Cited by 25 | Viewed by 6560
Abstract
Background: Child neglect is highly prevalent and associated with a series of biological and social consequences. Early neglect may alter the recognition of emotional faces, but its precise impact remains unclear. We aim to review and analyze data from recent literature about recognition [...] Read more.
Background: Child neglect is highly prevalent and associated with a series of biological and social consequences. Early neglect may alter the recognition of emotional faces, but its precise impact remains unclear. We aim to review and analyze data from recent literature about recognition and processing of facial expressions in individuals with history of childhood neglect. Methods: We conducted a systematic review using PubMed, PsycINFO, ScIELO and EMBASE databases in the search of studies for the past 10 years. Results: In total, 14 studies were selected and critically reviewed. A heterogeneity was detected across methods and sample frames. Results were mixed across studies. Different forms of alterations to perception of facial expressions were found across 12 studies. There was alteration to the recognition and processing of both positive and negative emotions, but for emotional face processing there was predominance in alteration toward negative emotions. Conclusions: This is the first review to examine specifically the effects of early neglect experience as a prevalent condition of child maltreatment. The results of this review are inconclusive due to methodological diversity, implement of distinct instruments and differences in the composition of the samples. Despite these limitations, some studies support our hypothesis that individuals with history of early negligence may present alteration to the ability to perceive face expressions of emotions. The article brings relevant information that can help in the development of more effective therapeutic strategies to reduce the impact of neglect on the cognitive and emotional development of the child. Full article
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19 pages, 1773 KiB  
Article
Behavioral and Brain Activity Indices of Cognitive Control Deficits in Binge Drinkers
by Sean M. Molnar, Lauren E. Beaton, Joseph P. Happer, Lee A. Holcomb, Siyuan Huang, Donatello Arienzo and Ksenija Marinkovic
Brain Sci. 2018, 8(1), 9; https://doi.org/10.3390/brainsci8010009 - 04 Jan 2018
Cited by 15 | Viewed by 7325
Abstract
Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging [...] Read more.
Heavy episodic drinking is prevalent among young adults and is a public issue of increasing importance. Its initiation and maintenance are associated with deficits in the capacity to inhibit automatic processing in favor of non-habitual responses. This study used functional magnetic resonance imaging (fMRI) to examine behavioral and brain activity indices of cognitive control during the Stroop task as a function of binge drinking. Heavy episodic drinkers (HED) reported consuming 5+/6+ drinks in two hours at least five times in the past six months and were compared to light drinkers (LED) who reported two or fewer binge episodes but were matched on demographics, intelligence and family history of alcoholism. Greater conflict-induced activity in the ventrolateral prefrontal cortex (VLPFC) and thalamus was observed in HED participants and it was positively correlated with alcohol intake and alcohol-related harmful consequences. HEDs maintained intact accuracy but at a cost of prolonged reaction times to high-conflict trials and increased ratings of task difficulty. Greater activation of the areas implicated in cognitive control is consistent with compensatory network expansion to meet higher cognitive demands. These results provide further insight into degradation of cognitive control in HEDs which may benefit development of detection and prevention strategies. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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22 pages, 548 KiB  
Article
Local Choices: Rationality and the Contextuality of Decision-Making
by Ivo Vlaev
Brain Sci. 2018, 8(1), 8; https://doi.org/10.3390/brainsci8010008 - 02 Jan 2018
Cited by 16 | Viewed by 5802
Abstract
Rational explanation is ubiquitous in psychology and social sciences, ranging from rational analysis, expectancy-value theories, ideal observer models, mental logic to probabilistic frameworks, rational choice theory, and informal “folk psychological” explanation. However, rational explanation appears to be challenged by apparently systematic irrationality observed [...] Read more.
Rational explanation is ubiquitous in psychology and social sciences, ranging from rational analysis, expectancy-value theories, ideal observer models, mental logic to probabilistic frameworks, rational choice theory, and informal “folk psychological” explanation. However, rational explanation appears to be challenged by apparently systematic irrationality observed in psychological experiments, especially in the field of judgement and decision-making (JDM). Here, it is proposed that the experimental results require not that rational explanation should be rejected, but that rational explanation is local, i.e., within a context. Thus, rational models need to be supplemented with a theory of contextual shifts. We review evidence in JDM that patterns of choices are often consistent within contexts, but unstable between contexts. We also demonstrate that for a limited, though reasonably broad, class of decision-making domains, recent theoretical models can be viewed as providing theories of contextual shifts. It is argued that one particular significant source of global inconsistency arises from a cognitive inability to represent absolute magnitudes, whether for perceptual variables, utilities, payoffs, or probabilities. This overall argument provides a fresh perspective on the scope and limits of human rationality. Full article
(This article belongs to the Special Issue Neurological Research on Learning, Reward and Decision Making)
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1585 KiB  
Article
Preliminary Findings that a Targeted Intervention Leads to Altered Brain Function in Children with Fetal Alcohol Spectrum Disorder
by Kelly Nash, Sara Stevens, Hayyah Clairman and Joanne Rovet
Brain Sci. 2018, 8(1), 7; https://doi.org/10.3390/brainsci8010007 - 28 Dec 2017
Cited by 17 | Viewed by 8619
Abstract
Children with fetal alcohol spectrum disorder (FASD) exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral [...] Read more.
Children with fetal alcohol spectrum disorder (FASD) exhibit behavioral dysregulation, executive dysfunction, and atypical function in associated brain regions. Previous research shows early intervention mitigates these outcomes but corresponding brain changes were not studied. Given the Alert® Program for Self-Regulation improves behavioral regulation and executive function in children with FASD, we asked if this therapy also improves their neural functioning in associated regions. Twenty-one children with FASD aged 8–12 years were randomized to the Alert®-treatment (TXT; n = 10) or waitlist-control (WL; n = 11) conditions. They were assessed with a Go-NoGo functional magnetic resonance imaging (fMRI) paradigm before and after training or the wait-out period. Groups initially performed equivalently and showed no fMRI differences. At post-test, TXT outperformed WL on NoGo trials while fMRI in uncorrected results with a small-volume correction showed less activation in prefrontal, temporal, and cingulate regions. Groups also demonstrated different patterns of change over time reflecting reduced signal at post-test in selective prefrontal and parietal regions in TXT and increased in WL. In light of previous evidence indicating TXT at post-test perform similar to non-exposed children on the Go-NoGo fMRI paradigm, our findings suggest Alert® does improve functional integrity in the neural circuitry for behavioral regulation in children with FASD. Full article
(This article belongs to the Special Issue Alcohol Induced Central Nervous System Damage)
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818 KiB  
Article
Emotional Encoding Context Leads to Memory Bias in Individuals with High Anxiety
by Christopher Lee and Myra A. Fernandes
Brain Sci. 2018, 8(1), 6; https://doi.org/10.3390/brainsci8010006 - 27 Dec 2017
Cited by 5 | Viewed by 1887797
Abstract
We investigated whether anxious individuals, who adopt an inherently negative mindset, demonstrate a particularly salient memory bias for words tainted by negative contexts. To this end, sequentially presented target words, overlayed onto negative or neutral pictures, were studied in separate blocks (within-subjects) using [...] Read more.
We investigated whether anxious individuals, who adopt an inherently negative mindset, demonstrate a particularly salient memory bias for words tainted by negative contexts. To this end, sequentially presented target words, overlayed onto negative or neutral pictures, were studied in separate blocks (within-subjects) using a deep or shallow encoding instruction (between-subjects). Following study, in Test 1, participants completed separate recognition test blocks for the words overlayed onto the negative and the neutral contexts. Following this, in Test 2, participants completed a recognition test for the foils from each Test 1 block. We found a significant three-way interaction on Test 2, such that individuals with high anxiety who initially studied target words using a shallow encoding instruction, demonstrated significantly elevated memory for foils that were contained within the negative Test 1 block. Results show that during retrieval (Test 1), participants re-entered the mode of processing (negative or neutral) engaged at encoding, tainting the encoding of foils with that same mode of processing. The findings suggest that individuals with high relative to low anxiety, adopt a particularly salient negative retrieval mode, and this creates a downstream bias in encoding and subsequent retrieval of otherwise neutral information. Full article
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1604 KiB  
Article
Extent of Resection in Newly Diagnosed Glioblastoma: Impact of a Specialized Neuro-Oncology Care Center
by Amer Haj, Christian Doenitz, Karl-Michael Schebesch, Denise Ehrensberger, Peter Hau, Kurt Putnik, Markus J. Riemenschneider, Christina Wendl, Michael Gerken, Tobias Pukrop, Alexander Brawanski and Martin A. Proescholdt
Brain Sci. 2018, 8(1), 5; https://doi.org/10.3390/brainsci8010005 - 25 Dec 2017
Cited by 43 | Viewed by 5684
Abstract
Treatment of glioblastoma (GBM) consists of microsurgical resection followed by concomitant radiochemotherapy and adjuvant chemotherapy. The best outcome regarding progression free (PFS) and overall survival (OS) is achieved by maximal resection. The foundation of a specialized neuro-oncology care center (NOC) has enabled the [...] Read more.
Treatment of glioblastoma (GBM) consists of microsurgical resection followed by concomitant radiochemotherapy and adjuvant chemotherapy. The best outcome regarding progression free (PFS) and overall survival (OS) is achieved by maximal resection. The foundation of a specialized neuro-oncology care center (NOC) has enabled the implementation of a large technical portfolio including functional imaging, awake craniotomy, PET scanning, fluorescence-guided resection, and integrated postsurgical therapy. This study analyzed whether the technically improved neurosurgical treatment structure yields a higher rate of complete resection, thus ultimately improving patient outcome. Patients and methods: The study included 149 patients treated surgically for newly diagnosed GBM. The neurological performance score (NPS) and the Karnofsky performance score (KPS) were measured before and after resection. The extent of resection (EOR) was volumetrically quantified. Patients were stratified into two subcohorts: treated before (A) and after (B) the foundation of the Regensburg NOC. The EOR and the PFS and OS were evaluated. Results: Prognostic factors for PFS and OS were age, preoperative KPS, O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status, isocitrate dehydrogenase 1 (IDH1) mutation status and EOR. Patients with volumetrically defined complete resection had significantly better PFS (9.4 vs. 7.8 months; p = 0.042) and OS (18.4 vs. 14.5 months; p = 0.005) than patients with incomplete resection. The frequency of transient or permanent postoperative neurological deficits was not higher after complete resection in both subcohorts. The frequency of complete resection was significantly higher in subcohort B than in subcohort A (68.2% vs. 34.8%; p = 0.007). Accordingly, subcohort B showed significantly longer PFS (8.6 vs. 7.5 months; p = 0.010) and OS (18.7 vs. 12.4 months; p = 0.001). Multivariate Cox regression analysis showed complete resection, age, preoperative KPS, and MGMT promoter status as independent prognostic factors for PFS and OS. Our data show a higher frequency of complete resection in patients with GBM after the establishment of a series of technical developments that resulted in significantly better PFS and OS without increasing surgery-related morbidity. Full article
(This article belongs to the Special Issue Advances in Adult and Pediatric Brain Tumor Management)
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1400 KiB  
Article
Adaptive Deep Brain Stimulation (aDBS) for Tourette Syndrome
by Sara Marceglia, Manuela Rosa, Domenico Servello, Mauro Porta, Sergio Barbieri, Elena Moro and Alberto Priori
Brain Sci. 2018, 8(1), 4; https://doi.org/10.3390/brainsci8010004 - 23 Dec 2017
Cited by 24 | Viewed by 6173
Abstract
Deep brain stimulation (DBS) has emerged as a novel therapy for the treatment of several movement and neuropsychiatric disorders, and may also be suitable for the treatment of Tourette syndrome (TS). The main DBS targets used to date in patients with TS are [...] Read more.
Deep brain stimulation (DBS) has emerged as a novel therapy for the treatment of several movement and neuropsychiatric disorders, and may also be suitable for the treatment of Tourette syndrome (TS). The main DBS targets used to date in patients with TS are located within the basal ganglia-thalamo-cortical circuit involved in the pathophysiology of this syndrome. They include the ventralis oralis/centromedian-parafascicular (Vo/CM-Pf) nucleus of the thalamus and the nucleus accumbens. Current DBS treatments deliver continuous electrical stimulation and are not designed to adapt to the patient’s symptoms, thereby contributing to unwanted side effects. Moreover, continuous DBS can lead to rapid battery depletion, which necessitates frequent battery replacement surgeries. Adaptive deep brain stimulation (aDBS), which is controlled based on neurophysiological biomarkers, is considered one of the most promising approaches to optimize clinical benefits and to limit the side effects of DBS. aDBS consists of a closed-loop system designed to measure and analyse a control variable reflecting the patient’s clinical condition and to modify on-line stimulation settings to improve treatment efficacy. Local field potentials (LFPs), which are sums of pre- and post-synaptic activity arising from large neuronal populations, directly recorded from electrodes implanted for DBS can theoretically represent a reliable correlate of clinical status in patients with TS. The well-established LFP-clinical correlations in patients with Parkinson’s disease reported in the last few years provide the rationale for developing and implementing new aDBS devices whose efficacies are under evaluation in humans. Only a few studies have investigated LFP activity recorded from DBS target structures and the relationship of this activity to clinical symptoms in TS. Here, we review the available literature supporting the feasibility of an LFP-based aDBS approach in patients with TS. In addition, to increase such knowledge, we report explorative findings regarding LFP data recently acquired and analysed in patients with TS after DBS electrode implantation at rest, during voluntary and involuntary movements (tics), and during ongoing DBS. Data available up to now suggest that patients with TS have oscillatory patterns specifically associated with the part of the brain they are recorded from, and thereby with clinical manifestations. The Vo/CM-Pf nucleus of the thalamus is involved in movement execution and the pathophysiology of TS. Moreover, the oscillatory patterns in TS are specifically modulated by DBS treatment, as reflected by improvements in TS symptoms. These findings suggest that LFPs recorded from DBS targets may be used to control new aDBS devices capable of adaptive stimulation responsive to the symptoms of TS. Full article
(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)
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607 KiB  
Article
A Prospective Birth Cohort Study on Maternal Cholesterol Levels and Offspring Attention Deficit Hyperactivity Disorder: New Insight on Sex Differences
by Yuelong Ji, Anne W. Riley, Li-Ching Lee, Heather Volk, Xiumei Hong, Guoying Wang, Rayris Angomas, Tom Stivers, Anastacia Wahl, Hongkai Ji, Tami R. Bartell, Irina Burd, David Paige, Margaret D. Fallin, Barry Zuckerman and Xiaobin Wang
Brain Sci. 2018, 8(1), 3; https://doi.org/10.3390/brainsci8010003 - 23 Dec 2017
Cited by 14 | Viewed by 5990
Abstract
Growing evidence suggests that maternal cholesterol levels are important in the offspring’s brain growth and development. Previous studies on cholesterols and brain functions were mostly in adults. We sought to examine the prospective association between maternal cholesterol levels and the risk of attention [...] Read more.
Growing evidence suggests that maternal cholesterol levels are important in the offspring’s brain growth and development. Previous studies on cholesterols and brain functions were mostly in adults. We sought to examine the prospective association between maternal cholesterol levels and the risk of attention deficit hyperactivity disorder (ADHD) in the offspring. We analyzed data from the Boston Birth Cohort, enrolled at birth and followed from birth up to age 15 years. The final analyses included 1479 mother-infant pairs: 303 children with ADHD, and 1176 neurotypical children without clinician-diagnosed neurodevelopmental disorders. The median age of the first diagnosis of ADHD was seven years. The multiple logistic regression results showed that a low maternal high-density lipoprotein level (≤60 mg/dL) was associated with an increased risk of ADHD, compared to a higher maternal high-density lipoprotein level, after adjusting for pertinent covariables. A “J” shaped relationship was observed between triglycerides and ADHD risk. The associations with ADHD for maternal high-density lipoprotein and triglycerides were more pronounced among boys. The findings based on this predominantly urban low-income minority birth cohort raise a new mechanistic perspective for understanding the origins of ADHD and the gender differences and future targets in the prevention of ADHD. Full article
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1496 KiB  
Review
Stimulation and Neuromodulation in the Treatment of Epilepsy
by Timothy Marc Eastin and Miguel Angel Lopez-Gonzalez
Brain Sci. 2018, 8(1), 2; https://doi.org/10.3390/brainsci8010002 - 21 Dec 2017
Cited by 12 | Viewed by 5688
Abstract
Invasive brain stimulation technologies are allowing the improvement of multiple neurological diseases that were non-manageable in the past. Nowadays, this technology is widely used for movement disorders and is undergoing multiple clinical and basic science research for development of new applications. Epilepsy is [...] Read more.
Invasive brain stimulation technologies are allowing the improvement of multiple neurological diseases that were non-manageable in the past. Nowadays, this technology is widely used for movement disorders and is undergoing multiple clinical and basic science research for development of new applications. Epilepsy is one of the conditions that can benefit from these emerging technologies. The objective of this manuscript is to review literature about historical background, current principles and outcomes of available modalities of neuromodulation and deep brain stimulation in epilepsy patients. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy)
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2668 KiB  
Article
Disturbed Glucose Metabolism in Rat Neurons Exposed to Cerebrospinal Fluid Obtained from Multiple Sclerosis Subjects
by Deepali Mathur, Eva María-Lafuente, Juan R. Ureña-Peralta, Lucas Sorribes, Alberto Hernández, Bonaventura Casanova, Gerardo López-Rodas, Francisco Coret-Ferrer and Maria Burgal-Marti
Brain Sci. 2018, 8(1), 1; https://doi.org/10.3390/brainsci8010001 - 21 Dec 2017
Cited by 3 | Viewed by 5192
Abstract
Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate [...] Read more.
Axonal damage is widely accepted as a major cause of permanent functional disability in Multiple Sclerosis (MS). In relapsing-remitting MS, there is a possibility of remyelination by myelin producing cells and restoration of neurological function. The purpose of this study was to delineate the pathophysiological mechanisms underpinning axonal injury through hitherto unknown factors present in cerebrospinal fluid (CSF) that may regulate axonal damage, remyelinate the axon and make functional recovery possible. We employed primary cultures of rat unmyelinated cerebellar granule neurons and treated them with CSF obtained from MS and Neuromyelitis optica (NMO) patients. We performed microarray gene expression profiling to study changes in gene expression in treated neurons as compared to controls. Additionally, we determined the influence of gene-gene interaction upon the whole metabolic network in our experimental conditions using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) program. Our findings revealed the downregulated expression of genes involved in glucose metabolism in MS-derived CSF-treated neurons and upregulated expression of genes in NMO-derived CSF-treated neurons. We conclude that factors in the CSF of these patients caused a perturbation in metabolic gene(s) expression and suggest that MS appears to be linked with metabolic deformity. Full article
(This article belongs to the Special Issue Pathogenesis and Treatment of Neurodegenerative Diseases)
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