Brain Sci., Volume 10, Issue 11 (November 2020) – 135 articles

Deaf and Hard of Hearing (DHH) children show difficulties in reading aloud and comprehension of texts. Here, we examined the hypothesis that these reading difficulties are tightly related to the syntactic deficit displayed by DHH children. We first assessed the syntactic abilities of 32 DHH children communicating in spoken language (Hebrew) aged 9;1–12;2. We classified them into two groups of DHH children—with and without a syntactic deficit according to their performance in six syntactic tests assessing their comprehension and production of sentences with syntactic movement. We also assessed their reading at the single word level using a reading aloud test of words, nonwords, and word pairs, designed to detect the various types of dyslexia, and established, for each participant, whether they had dyslexia and of what type. Following this procedure, 14 of the children were identified with a syntactic deficit, and 15 with typical syntax (3 marginally impaired); 22 of the children had typical reading at the word level, and 4 had dyslexia (3 demonstrated sublexical reading). The main experiment examined reading aloud and comprehension of 6 texts with syntactic movement (which contained, e.g., relative clauses and topicalized sentences), in comparison to 6 parallel texts without movement. The results indicated a close connection between syntactic difficulties and errors in reading aloud and in comprehension of texts. The DHH children with syntactic deficit made significantly more errors in reading aloud and more comprehension errors than the DHH children with intact syntax (and than the hearing controls), even though most of them did not have dyslexia at the word level. The DHH children with syntactic deficit made significantly more reading errors when they read texts with syntactic movement than on matched texts without movement. These results indicate that difficulties in text reading, manifesting both in errors in reading aloud and in impaired comprehension, may stem from a syntactic deficit and may occur even when reading at the word level is completely intact. Full article

The recreational use of opioid drugs is a global threat to public health and safety. In particular, an epidemic of opioid overdose fatalities is being driven by illicitly manufactured fentanyl, while novel synthetic opioids (NSOs) are appearing on recreational drug markets as standalone products, adulterants in heroin, or ingredients in counterfeit drug preparations. Trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) is a prime example of a non-fentanyl NSO that is associated with numerous intoxications and fatalities. Here, we review the medicinal chemistry, preclinical pharmacology, clandestine availability, methods for detection, and forensic toxicology of U-47700 and its analogs. An up-to-date summary of the human cases involving U-47700 intoxication and death are described. The evidence demonstrates that U-47700 is a potent μ-opioid receptor agonist, which poses a serious risk for overdosing and death. However, most analogs of U-47700 appear to be less potent and have been detected infrequently in forensic specimens. U-47700 represents a classic example of how chemical entities from the medicinal chemistry or patent literature can be diverted for use in recreational drug markets. Lessons learned from the experiences with U-47700 can inform scientists, clinicians, and policymakers who are involved with responding to the spread and impact of NSOs. Full article

The medial olivocochlear (MOC) system is thought to be responsible for modulation of peripheral hearing through descending (efferent) pathways. This study investigated the connection between peripheral hearing function and conscious attention during two different modality tasks, auditory and visual. Peripheral hearing function was evaluated by analyzing the amount of suppression of otoacoustic emissions (OAEs) by contralateral acoustic stimulation (CAS), a well-known effect of the MOC. Simultaneously, attention was evaluated by event-related potentials (ERPs). Although the ERPs showed clear differences in processing of auditory and visual tasks, there were no differences in the levels of OAE suppression. We also analyzed OAEs for the highest magnitude resonant mode signal detected by the matching pursuit method, but again did not find a significant effect of task, and no difference in noise level or number of rejected trials. However, for auditory tasks, the amplitude of the P3 cognitive wave negatively correlated with the level of OAE suppression. We conclude that there seems to be no change in MOC function when performing different modality tasks, although the cortex still remains able to modulate some aspects of MOC activity. Full article

Transplantation of neural stem cells (NSCs) has been proposed as an alternative novel therapy to replace damaged neural circuitry after ischemic stroke onset. Nonetheless, albeit the potential of these cells for stroke therapy, many critical challenges are yet to be overcome to reach clinical applications. The major limitation of the NSC-based therapy is its inability to retain most of the donor stem cells after grafting into an ischemic brain area which is lacking of essential oxygen and nutrients for the survival of transplanted cells. Low cell survival rate limits the capacity of NSCs to repair the injured area and this poses a much more difficult challenge to the NSC-based therapy for ischemic stroke. In order to enhance the survival of transplanted cells, several stem cell culture preconditioning strategies have been employed. For ischemic diseases, hypoxic preconditioning is the most commonly applied strategy since the last few decades. Now, the preconditioning strategies have been developed and expanded enormously throughout years of efforts. This review systematically presented studies searched from PubMed, ScienceDirect, Web of Science, Scopus and the Google Scholar database up to 31 March 2020 based on search words containing the following terms: “precondition” or “pretreatment” and “neural stem cell” and “ischemic stroke”. The searched data comprehensively reported seven major NSC preconditioning strategies including hypoxic condition, small drug molecules such as minocycline, doxycycline, interleukin-6, adjudin, sodium butyrate and nicorandil, as well as electrical stimulation using conductive polymer for ischemic stroke treatment. We discussed therapeutic benefits gained from these preconditioned NSC for in vitro and in vivo stroke studies and the detailed insights of the mechanisms underlying these preconditioning approaches. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of these preconditioned NSCs in human clinical studies, therefore, it is still too early to draw a definitive conclusion on the efficacy and safety of this active compound for patient usage. Thus, we suggest for more in-depth clinical investigations of this cell-based therapy to develop into more conscientious and judicious evidence-based therapy for clinical application in the future. Full article

Dravet Syndrome (DS) is burdened by high epilepsy-related premature mortality due to status epilepticus (SE). We surveyed centres within Europe through the Dravet Italia Onlus and EpiCARE network (European Reference Network for Rare and Complex Epilepsies). We collated responses on seven DS SCN1A+ patients who died following refractory SE (mean age 6.9 year, range 1.3–23.4 year); six were on valproate, clobazam, and stiripentol. All patients had previous SE. Fatal SE was always triggered by fever: either respiratory infection or one case of hexavalent vaccination. SE lasted between 80 min and 9 h and all patients received IV benzodiazepines. Four patients died during or within hours of SE; in three patients, SE was followed by coma with death occurring after 13–60 days. Our survey supports the hypothesis that unresponsive fever is a core characteristic feature of acute encephalopathy. We highlight the need for management protocols for prolonged seizures and SE in DS. Full article

During the three-month closure of clinics and day centers in Iran due to the coronavirus disease 2019 (COVID-19) lockdown, parents of children with Autism Spectrum Disorder (ASD) became solely responsible for their care and education. Although centers maintained telephone contact, it quickly became evident that parents needed more detailed advice and guidance. Staff from 30 daycare centers volunteered to take part in a two-month online support and training course for 336 caregivers of children with ASD of different ages. In addition to the provision of visual and written information, synchronous video sessions were used to coach parents on the learning goals devised for the children. Both qualitative and quantitative data were collected to understand the acceptability of using telepractice and the outcomes achieved. A low dropout rate and positive feedback from parents indicated that they perceived telepractice sessions to be useful. The factors contributing to parents’ satisfaction were identified. Although the use of telepractice would be a good alternative for caregivers in any future lockdowns, it could also be used in conjunction with daycare center services to encourage greater parental participation, or with families living in areas with no day centers. Further studies are needed to compare telepractice to usual daycare face-to-face interventions, and to document its impact and cost-effectiveness for parents and children. Full article

Background: Childcare programs often include mandatory naptime during the day. Loss of daytime sleep could lead to a moderate-to-large decrease in self-regulation, emotion processing, and learning in early childhood. Nevertheless, daytime sleep has been less accurately studied than nighttime sleep. This study aims to explore the relationship between diurnal sleep habits in nursery settings, nocturnal sleep quality, and post-nap emotional intensity in infants and toddlers. Methods: Data of 92 children (52 girls, 40 boys) aged 6 to 36 months were obtained. Sleep habits as well as positive and negative emotions were monitored by educators during nursery times through a sleep and emotion diary for two weeks. Results: Explorative analyses showed that diurnal sleep hours decreased across age groups (except for females aged 25–36 months) and that all age groups had a lower amount of nocturnal sleep than is recommended by the National Sleep Foundation. Partial correlation analysis showed significant correlation between daytime sleep onset latency and positive emotions. Mediation analyses showed that daytime napping is relevant for emotional functioning independently of nocturnal sleep quality. Conclusions: Daytime sleep in early childhood seems to be linked to the management of positive and negative emotions and could play a role in healthy development of emotional processes. Full article

Ultrasonic vocalizations (USVs) are well-established markers of motivational and emotional status. Recent work from our lab has provided novel evidence for a role of USVs in models of ethanol (EtOH) use. For instance, USV acoustic characteristics can be used to accurately discriminate between rats selectively bred for high EtOH intake (e.g., alcohol-preferring (P) and high-alcohol-drinking (HAD)) versus EtOH-avoiding (e.g., alcohol-non-preferring (NP) and low-alcohol-drinking (LAD)) strains, as well as differentiate between male and female rats. In the present study we sought to explore the effect of age and alcohol availability on spontaneously emitted 50–55 kHz frequency modulated (FM) and 22–28 kHz USVs in adult, male Long–Evans rats. With the hypothesis that age and alcohol experience influence spontaneous USV emissions, we examined USV data collected across a 24-week intermittent EtOH access experiment in male Long–Evans rats. USV counts and acoustic characteristic (i.e., mean frequency, duration, bandwidth and power) data revealed distinct age-dependent phenotypes in both 50–55 kHz FM and 22–28 kHz USV transmission patterns that were modulated by EtOH exposure. These results highlight the influence of age and EtOH experience on the unique emotional phenotypes of male Long–Evans rats. Full article

Background: Low intensity, high-frequency transcranial alternating current stimulation (tACS) applied over the motor cortex decreases the amplitude of motor evoked potentials. This double-blind, placebo-controlled parallel group study aimed to test the efficacy of this method for acute management of migraines. Methods: The patients received either active (0.4 mA, 140 Hz) or sham stimulation for 15 min over the visual cortex with the number of terminated attacks two hours post-stimulation as the primary endpoint, as a home therapy option. They were advised to treat a maximum of five migraine attacks over the course of six weeks. Results: From forty patients, twenty-five completed the study, sixteen in the active and nine in the sham group with a total of 102 treated migraine attacks. The percentage of terminated migraine attacks not requiring acute rescue medication was significantly higher in the active (21.5%) than in the sham group (0%), and the perceived pain after active stimulation was significantly less for 2–4 h post-stimulation than after sham stimulation. Conclusion: tACS over the visual cortex has the potential to terminate migraine attacks. Nevertheless, the high drop-out rate due to compliance problems suggests that this method is impeded by its complexity and time-consuming setup. Full article

Several studies in children with neurodevelopmental disorders (NDDs) including autism spectrum disorders (ASDs), reading impairment, or attention deficit/hyperactive disorder (ADHD) pointed toward a potential dysfunction of the vestibular system, specifically in its complex relationship with the cerebellum. The aim of the present study was to test the functional vestibulo-ocular reflex (VOR) responses in children with NDDs to measure functional performance of the vestibular system. The VOR is specifically involved in this stabilization of the image on the retina during rapid movements of the head. To perform this study, four groups of children with ASD, ADHD, reading impairment, and with neurotypical development (TD) were enrolled (n = 80). We performed the functional head impulse test (fHIT), which measured the percentage of correct responses by asking the child to identify an optotype briefly presented during passive head impulse in each direction of each semicircular canal plane. We observed significantly lower correct answers in children with NDDs compared with those with TD (p < 0.0001). Surprisingly, there was no significant difference between the three groups of children with NDDs. Our study fostered preliminary evidence suggesting altered efficiency of vestibular system in children with NDDs. VOR abnormalities estimated using the fHIT could be used as a proxy of NDD impairments in children, and represent a potential biomarker. Full article

This study aimed to differentiate primary central nervous system lymphoma (PCNSL) and glioblastoma (GBM) via multimodal MRI featuring radiomic analysis. MRI data sets of patients with histological proven PCNSL and GBM were analyzed retrospectively. Diffusion-weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion imaging were evaluated to differentiate contrast enhancing intracerebral lesions. Selective (contrast enhanced tumor area with the highest mean cerebral blood volume (CBV) value) and unselective (contouring whole contrast enhanced lesion) Apparent diffusion coefficient (ADC) measurement was performed. By multivariate logistic regression, a multiparametric model was compiled and tested for its diagnostic strength. A total of 74 patients were included in our study. Selective and unselective mean and maximum ADC values, mean and maximum CBV and ratio_CBV as quotient of tumor CBV and CBV in contralateral healthy white matter were significantly larger in patients with GBM than PCNSL; minimum CBV was significantly lower in GBM than in PCNSL. The highest AUC for discrimination of PCNSL and GBM was obtained for selective mean and maximum ADC, mean and maximum CBV and ratio_CBV. By integrating these five in a multiparametric model 100% of the patients were classified correctly. The combination of perfusion imaging (CBV) and tumor hot-spot selective ADC measurement yields reliable radiological discrimination of PCNSL from GBM with highest accuracy and is readily available in clinical routine. Full article

Neonatal seizures are the most common neurological emergency, and neonatal status epilepticus (NSE) remains a controversial entity, with no general consensus about its definition and treatment. Here, we report on three newborns with NSE refractory to first- and second-line antiepileptic drugs successfully treated with intravenous (IV) hydrocortisone. The patients had previously failed therapy with levetiracetam, phenobarbital and midazolam, showing persistent clinical and electrical seizures. Modulation of brain inflammation triggered during prolonged epileptic activity has been thought to potentially explain the beneficial effects of anti-inflammatory treatment. Full article

Gulf War illness (GWI) refers to the multitude of chronic health symptoms, spanning from fatigue, musculoskeletal pain, and neurological complaints to respiratory, gastrointestinal, and dermatologic symptoms experienced by about 250,000 GW veterans who served in the 1991 Gulf War (GW). Longitudinal studies showed that the severity of these symptoms often remain unchanged even years after the GW, and these veterans with GWI continue to have poorer general health and increased chronic medical conditions than their non-deployed counterparts. For better management and treatment of this condition, there is an urgent need for developing objective biomarkers that can help with simple and accurate diagnosis of GWI. In this study, we applied multiple neuroimaging techniques, including T1-weighted magnetic resonance imaging (T1W-MRI), diffusion tensor imaging (DTI), and novel neurite density imaging (NDI) to perform both a group-level statistical comparison and a single-subject level machine learning (ML) analysis to identify diagnostic imaging features of GWI. Our results supported NDI as the most sensitive in defining GWI characteristics. In particular, our classifier trained with white matter NDI features achieved an accuracy of 90% and F-score of 0.941 for classifying GWI cases from controls after the cross-validation. These results are consistent with our previous study which suggests that NDI measures are sensitive to the microstructural and macrostructural changes in the brain of veterans with GWI, which can be valuable for designing better diagnosis method and treatment efficacy studies. Full article

Introduction: Recent research has highlighted an increased rate of co-morbidity between the neurodevelopmental-behavioral disorder of attention deficit hyperactivity disorder (ADHD) and a variety of psychiatric disorders, such as mood disorders or bipolar disorder (BD). The etiology and clinical course of BD are considered to be determined by both genetic and environmental factors, either aggravating or improving. Aim: This follow-up study of an adolescent aimed to clarify the co-morbidity between ADHD and BD. We also discuss the controversies surrounding the two diagnoses in younger populations and describe several aspects of concern regarding diagnosis, differential diagnosis, therapeutic planning/intervention, and prognosis. Methods: Reporting of a two-year follow-up study of a bipolar 15-year-old female patient with a previous diagnosis of ADHD during childhood. Results: Despite the occurrence of major risk factors, such as early onset and positive family history, the patient’s condition rapidly remitted with medication, without relapse and/or rehospitalization during the following two years, due to the stability of her cooperation, and support of a stable and caring familial environment. Early diagnosis of BD and differential diagnoses of ADHD are considered crucial protective factors leading to an appropriate planning of treatment. In addition, parental involvement and empathic attitude towards the patient supported the latter to cooperate and comply with the treatment, enhancing positive outcomes and stability. Conclusions: Research is required into the reliability and validity of diagnostic protocols and criteria for BD in children and adolescents, and also into the development of individualized therapeutic planning. Full article

Prognosis of patients with acute ischemic stroke is strictly related to the patency and prominence of the collateral leptomeningeal pathways distal to the arterial occlusion. The gold standard for assessment of collateral circulation is conventional angiography, but it is invasive and used in selected cases. To date, the most reliable technique is multiphase CTA; currently, the available classifications of collateral circles are often complex, time-consuming, and require a trained observer. The purpose of our work is to establish the effectiveness of a new semi-automatic post-processing software (ColorViz FastStroke, GE Healthcare, Milwaukee, Wisconsin) in evaluation of collateral circulation compared to the six-point classifications of multiphase CTA already validated in literature. We selected 86 patients with anterior ischemic stroke symptoms who underwent multiphasic CTA in our emergency department. Two radiologists separately evaluated the collateral leptomeningeal vessels, analyzing respectively, the multiphase CTA (using the six-point scale and its trichotomized form) and ColorViz (using a three-point scale). Then the results were matched. We found a good correlation between the two different analyses; the main advantage of ColorViz is that, while maintaining fast diagnostic times, it allows a simpler and more immediate evaluation of collateral circulation, especially for less experienced radiologists. Full article

Arterial ischemic stroke (AIS) in childhood is reported to occur more frequently in boys, which may lead to the assumption that the prevalence of post-stroke deficits is sex related. The present study aimed to evaluate sex-related differences in functional outcomes (hemiparesis, seizures, aphasia, and motor disturbances other than hemiparesis) in pediatric patients with AIS. A total of 89 children (52 boys and 37 girls; mean age at stroke onset: 8.4 ± 5.6 years) were evaluated retrospectively based on data from medical records. The patients were divided into subgroups according to age (i.e., infants and toddlers, children, and adolescents), stroke subtype (i.e., lacunar anterior circulation infarct (LACI), total anterior circulation infarct (TACI), partial anterior circulation infarct (PACI), posterior circulation infarct (POCI)) and stroke location (i.e., anterior stroke, posterior stroke). Significant differences in the prevalence of stroke subtypes between girls and boys were observed (p = 0.034). POCI stroke were found to be more frequent in boys than in girls (OR = 8.57 95%CI 1.05–70.23, p = 0.023). Males predominated in the total group and in all analyzed age subgroups. The proportions of boys within the subgroups according to stroke subtype were extremely high for the POCI and TACI stroke subgroups. On the other hand, girls predominated in the LACI stroke subgroup. Frequency of central type facial nerve palsy and other symptoms of AIS were found to significantly differ between male subgroups according to stroke subtype (p = 0.050 and p < 0.001, respectively), as well as between children with anterior stroke and those with posterior stroke (p = 0.059 and p < 0.001, respectively). Post-stroke seizures appeared significantly more commonly in girls with TACI and POCI stroke than in girls with LACI and PACI stroke (p = 0.022). In turn, the prevalence of post-stroke hemiparesis differed between stroke subtypes in boys (p = 0.026). In conclusion, sex may have an impact in predisposing to a certain type of AIS in the patient. Post-stroke seizure may be related to stroke subtype in girls and hemiparesis in boys. However, further studies are needed to confirm the results. Full article

Effortful control (EC) is an important dimension of temperament, but is impaired in autism spectrum disorder (ASD). While EC is associated with the prefrontal cortex (PFC) functioning in typically developing (TD) children, it is unclear whether EC deficits are associated with PFC dysfunction in ASD. This study examines the relationship between EC and PFC activation and connectivity in children with high-functioning ASD. Thirty-nine right-handed children (ASD: n = 20; TD: n = 19) aged 8–12 years were recruited. The EC level was assessed with the Early Adolescent Temperament Questionnaire—Revised (EATQ-R), and PFC functioning, in terms of activation and connectivity during a frontal-sensitive (n-back) task, was assessed using functional near-infrared spectroscopy (fNIRS). Children with ASD showed a significant deficit in EC and its related constructs (i.e., executive, and socioemotional functions) compared to TD controls. They also showed significantly increased overall PFC activation and reduced right frontal connectivity during the n-back task. Among children with ASD, the EC level correlated significantly with neither PFC activation nor connectivity; it significantly correlated with social functioning only. This study demonstrated EC deficits and altered PFC functioning in children with ASD, but the exact neural basis of EC deficits remains to be determined. Full article

Modeling disease progression through the cognitive scores has become an attractive challenge in the field of computational neuroscience due to its importance for early diagnosis of Alzheimer’s disease (AD). Several scores such as Alzheimer’s Disease Assessment Scale cognitive total score, Mini Mental State Exam score and Rey Auditory Verbal Learning Test provide a quantitative assessment of the cognitive conditions of the patients and are commonly used as objective criteria for clinical diagnosis of dementia and mild cognitive impairment (MCI). On the other hand, connectivity patterns extracted from diffusion tensor imaging (DTI) have been successfully used to classify AD and MCI subjects with machine learning algorithms proving their potential application in the clinical setting. In this work, we carried out a pilot study to investigate the strength of association between DTI structural connectivity of a mixed ADNI cohort and cognitive spectrum in AD. We developed a machine learning framework to find a generalized cognitive score that summarizes the different functional domains reflected by each cognitive clinical index and to identify the connectivity biomarkers more significantly associated with the score. The results indicate that the efficiency and the centrality of some regions can effectively track cognitive impairment in AD showing a significant correlation with the generalized cognitive score (R = 0.7). Full article

Avenanthramides are a group of phenolic alkaloids that have been shown to have anti-inflammatory, anti-oxidant, anti-atherogenic, and vasodilation effects. The aim of the present study was to investigate the neuroprotective effect of avenanthramide-c (Avn-c) in focal brain ischemia and reperfusion injury using middle cerebral artery occlusion (MCAo) model with mice. Male C57BL/6 mice were divided into 4 groups: sham, control (MCAo), Avn-c, and Avn-c + LY294002 (phosphoinositide 3-kinase inhibitor) group. They were subjected to 60 min MCAo followed by reperfusion. Brain infarct volume and neurological deficit scores were measured after 24 h of reperfusion. We evaluated the blood brain barrier (BBB) integrity (ZO-1, VE-cadherin and occludin) and apoptosis (Bax, Bcl2, caspase3, Cytochrome C, and poly ADP ribose polymerase(PARP)-1). We also measured GSK3β for evaluation of the downstream mechanism of Akt. We examined the effect of the Avn-c in the phosphoinositide 3-kinase pathway. Avn-c reduced neurological score and infarction size. Avn-c inhibited the MCAo-induced disruption of tight junction proteins. Avn-c decreased apoptotic protein expression (Bax, Cytochrome C, and cleaved PARP-1) and increased anti-apoptotic protein expression (Bcl2) after MCAo. Akt and GSK3β were decreased in MCAo group and were restored in Avn-c group. This effect of Avn-c was abolished by PI3K inhibitor. In summary, Avn-c showed neuroprotective effects through PI3K-Akt-GSK3β signaling pathway. Full article

Studies on the structure of intelligence refer to two main theoretical models: the first one considers intelligence as a unitary construct, the second one assumes the involvement of a plurality of factors. Studies using Raven’s Coloured Progressive Matrices (RCPM) tasks have often highlighted the involvement of different cognitive abilities and brain structures, but in the clinical setting, RCPM measurement continues to be used as a single score. The current study aimed to analyse the RCPM performance following qualitative clustering, in order to provide an interpretation of the intelligence assessment through a factorial criterion. The RCPM have been administered to a large group of typically developing children between 6 and 11 years of age. The sample was divided into twelve age groups, and the performance of each age group was shown. Three qualitative item clusters were identified through a factorial criterion. Data showed that performance on RCPM may arise from different cognitive abilities, starting from basic attentional skills up to the more complex ones that require perceptual or analogical reasoning. The qualitative parameters could provide more effective diagnostic and treatment suggestions than a single total score in the clinical setting, and may be crucial for focusing on strength and weakness in the intellectual functionality evaluation of children. Full article

The relationship between alcohol consumption and traumatic brain injury (TBI) often focuses on alcohol consumption increasing the likelihood of incurring a TBI, rather than alcohol use outcomes after TBI. However, patients without a history of an alcohol use disorder can also show increased problem drinking after single or multiple TBIs. Alcohol and mild TBI share diffuse deleterious neurological impacts and cognitive impairments; therefore, the purpose of these studies was to determine if an interaction on brain and behavior outcomes occurs when alcohol is consumed longitudinally after TBI. To examine the impact of mild repetitive TBI (rmTBI) on voluntary alcohol consumption, mice were subjected to four mild TBI or sham procedures over a 2 week period, then offered alcohol (20% v/v) for 2 weeks using the two-bottle choice, drinking in the dark protocol. Following the drinking period, mice were evaluated for neuroinflammatory cytokine response or tested for cognitive and behavioral deficits. Results indicate no difference in alcohol consumption or preference following rmTBI as compared to sham; however, increases in the neuroinflammatory cytokine response due to alcohol consumption and some mild cognitive behavioral deficits after rmTBI and alcohol consumption were observed. These data suggest that the cytokine response to alcohol drinking and rmTBI + alcohol drinking is not necessarily aggregate, but the combination does result in an exacerbation of cognitive behavioral outcomes. Full article

A single session of priming cathodal transcranial direct current stimulation (tDCS) prior to anodal tDCS (c-a-tDCS) allows cumulative effects on motor learning and retention. However, the impact of multiple sessions of c-a-tDCS priming on learning and retention remains unclear. Here, we tested whether multiple sessions of c-a-tDCS (over 3 consecutive days) applied over the left sensorimotor cortex can further enhance motor learning and retention of an already learned visuo-motor task as compared to anodal tDCS (a-tDCS) or sham. In a between group and randomized double-blind sham-controlled study design, 25 participants separated in 3 independent groups underwent 2 days of baseline training without tDCS followed by 3-days of training with both online and offline tDCS, and two retention tests (1 and 14 days later). Each training block consisted of five trials of a 60 s circular-tracing task intersected by 60 s rest, and performance was assessed in terms of speed–accuracy trade-off represented notably by an index of performance (IP). The main findings of this exploratory study were that multiple sessions of c-a-tDCS significantly further enhanced IP above baseline training levels over the 3 training days that were maintained over the 2 retention days, but these learning and retention performance changes were not significantly different from the sham group. Subtle differences in the changes in speed–accuracy trade-off (components of IP) between c-a-tDCS (maintenance of accuracy over increasing speed) and a-tDCS (increasing speed over maintenance of accuracy) provide preliminary insights to a mechanistic modulation of motor performance with priming and polarity of tDCS. Full article

Our study evaluated the role of the T2–fluid-attenuated inversion recovery (FLAIR) mismatch sign in detecting isocitrate dehydrogenase (IDH) mutations based on a mixed sample of 24 patients with low- and high- grade gliomas. The association between the two was realized using univariate and multivariate logistic regression analysis. There was a substantial agreement between the two raters for the detection of the T2–FLAIR mismatch sign (Cohen’s kappa coefficient was 0.647). The T2–FLAIR mismatch sign when co-registered with the degree of tumor homogeneity were significant predictors of the IDH status (OR 29.642; 95% CI 1.73–509.15, p = 0.019). The probability of being IDH mutant in the presence of T2–FLAIR mismatch sign was as high as 92.9% (95% CI 63–99%). The sensitivity and specificity of T2–FLAIR mismatch sign in the detection of the IDH mutation was 88.9% and 86.7%, respectively. The T2–FLAIR mismatch sign may be an easy to use and helpful tool in recognizing IDH mutant patients, particularly if formal IDH testing is not available. We suggest that the adoption of a protocol based on imaging and histological data for optimal glioma characterization could be very helpful. Full article

Older adults with mild cognitive impairment (MCI) are at an increased risk for falls and fall-related injuries. It is unclear whether current balance rehabilitation techniques largely developed in cognitively intact populations would be successful in older adults with MCI. This mapping review examined the available balance rehabilitation research conducted in older adults with MCI. Databases Medline, Cinahl, Cochrane, PubMed, Scopus, and PsycINFO were systematically searched from inception to August 2020. Twenty-one studies with 16 original randomized controlled trials (RCTs) involving 1201 older adults with MCI (>age 60) met the inclusion criteria, of which 17 studies showed significant treatment effects on balance functions. However, only six studies demonstrated adequate quality (at least single-blind, no significant dropouts, and intervention and control groups are equivalent at baseline) and evidence (medium or large effect size on at least one balance outcome) in improving balance in this population, and none of them are double- or triple-blind. Therefore, more high-quality RCTs are needed to inform future balance rehabilitation program development for older adults with MCI. Moreover, few studies examined the incidence of falls after the intervention, which limits clinical utility. Future RCTs should prospectively monitor falls or changes in risk of falls after the intervention. Full article

Gliomas account for approximately 70% of primary brain tumors in adults. Of all gliomas, grade IV astrocytoma, also called glioblastoma, has the poorest overall survival, with <5% of patients surviving five years after diagnosis. Due to the aggressiveness, lethal nature, and impaired surgical accessibility of the tumor, early diagnosis of the tumor and, in addition, prediction of the patient’s survival time are important. We hypothesize that combining the protein level values of highly recognizable glioblastoma serum biomarkers could help to achieve higher specificity and sensitivity in predicting glioma patient outcome as compared to single markers. The aim of this study was to select the most promising astrocytoma patient overall survival prediction variables from five secretory proteins—glial fibrillary acidic protein (GFAP), matrix metalloproteinase-2 (MMP-2), chitinase 3-like 1 (CHI3L1), osteopontin (OPN), and amphiregulin (AREG)—combining them with routinely used tumor markers to create a Patient Survival Score calculation tool. The study group consisted of 70 astrocytoma patients and 31 healthy controls. We demonstrated that integrating serum CHI3L1 and OPN protein level values and tumor isocitrate dehydrogenase 1 IDH1 mutational status into one parameter could predict low-grade astrocytoma patients’ two-year survival with 93.8% accuracy. Full article

Slowing in information processing speed (IPS) is the key cognitive deficit in multiple sclerosis (MS). Testing IPS in different cognitive load conditions by using computerized tools might reveal initial IPS slowness underestimated by classic paper-and-pencil tests. To investigate the extent to which IPS can be affected by increased task demands, we developed three tasks based on the manipulation of the visual-attentional load, delivered with a home-made, tablet-based videogame. Fifty-one patients with MS (pwMS), classified as having no cognitive impairment in classic paper-and-pencil tests, and 20 healthy controls (HC) underwent the videogame tasks; reaction times (RTs) and accuracy were recorded. A significant reduced performance of pwMS as compared with HC was found on the videogame tasks, with pwMS being on average slower and less accurate than HC. Furthermore, pwMS showed a significantly more pronounced decrement in accuracy as a function of the visual-attentional load, suggesting a higher susceptibility to increased task demands. Significant correlations among the Symbol Digit Modalities Test (SDMT) and the videogame mean RTs and accuracy were found, providing evidence for the concurrent validity of the videogame as a valid tool to test IPS in pwMS. The high potential that might derive from the adoption of computerized assessment tools in clinical practice should be taken into consideration and investigated further. Full article

Brain waves, measured by electroencephalography (EEG), are a powerful tool in the investigation of neurophysiological traits and a noninvasive and cost-effective alternative in the diagnostic of some neurological diseases. In order to identify novel Quantitative Trait Loci (QTLs) for brain wave relative power (RP), we collected resting state EEG data in five frequency bands (δ, θ, α, β1, and β2) and genome-wide data in a cohort of 105 patients with late onset Alzheimer’s disease (LOAD), 41 individuals with mild cognitive impairment and 45 controls from Iberia, correcting for disease status. One novel association was found with an interesting candidate for a role in brain wave biology, CLEC16A (C-type lectin domain family 16), with a variant at this locus passing the adjusted genome-wide significance threshold after Bonferroni correction. This finding reinforces the importance of immune regulation in brain function. Additionally, at a significance cutoff value of 5 × 10⁻⁶, 18 independent association signals were detected. These signals comprise brain expression Quantitative Loci (eQTLs) in caudate basal ganglia, spinal cord, anterior cingulate cortex and hypothalamus, as well as chromatin interactions in adult and fetal cortex, neural progenitor cells and hippocampus. Moreover, in the set of genes showing signals of association with brain wave RP in our dataset, there is an overrepresentation of loci previously associated with neurological traits and pathologies, evidencing the pleiotropy of the genetic variation modulating brain function. Full article

Leukoencephalopathy with calcifications and cysts (LCC) is a triad of neuroradiological symptoms characteristic of Labrune syndrome, which was first described in 1996. For 20 years, the diagnosis was only based on clinical, neuroradiological and histopathological findings. Differential diagnosis included a wide spectrum of diseases. Finally, in 2016, genetic mutation in the SNORD118 gene was confirmed to cause Labrune syndrome. The authors describe a case of a teenage girl with progressive headaches, without developmental delay, presenting with calcifications and white matter abnormality in neuroimaging. Follow-up studies showed the progression of leukoencephalopathy and cyst formation. The first symptoms and initial imaging results posed diagnostic challenges. The final diagnosis was established based on genetic results. The authors discuss the possible therapy of LCC with Bevacizumab. Full article

The glymphatic system is a “pseudo-lymphatic” perivascular network distributed throughout the brain, responsible for replenishing as well as cleansing the brain. Glymphatic clearance is the macroscopic process of convective fluid transport in which harmful interstitial metabolic waste products are removed from the brain intima. This paper addresses the glymphatic system, its dysfunction and the major consequences of impaired clearance in order to link neurodegeneration and glymphatic activity with lifestyle choices. Glymphatic clearance can be manipulated by sleep deprivation, cisterna magna puncture, acetazolamide or genetic deletion of AQP4 channels, but how lifestyle choices affect this brain-wide clearance system remains to be resolved. This paper will synthesize existing literature on glymphatic clearance, sleep, Alzheimer’s disease and lifestyle choices, in order to harness the power of this mass transport system, promote healthy brain ageing and possibly prevent neurodegenerative processes. This paper concludes that 1. glymphatic clearance plays a major role in Alzheimer’s pathology; 2. the vast majority of waste clearance occurs during sleep; 3. dementias are associated with sleep disruption, alongside an age-related decline in AQP4 polarization; and 4. lifestyle choices such as sleep position, alcohol intake, exercise, omega-3 consumption, intermittent fasting and chronic stress all modulate glymphatic clearance. Lifestyle choices could therefore alter Alzheimer’s disease risk through improved glymphatic clearance, and could be used as a preventative lifestyle intervention for both healthy brain ageing and Alzheimer’s disease. Full article

Tinnitus is a complex and heterogeneous psycho-physiological disorder responsible for causing a phantom ringing or buzzing sound albeit the absence of an external sound source. It has a direct influence on affecting the quality of life of its sufferers. Despite being around for a while, there has not been a cure for tinnitus, and the usual course of action for its treatment involves use of tinnitus retaining and sound therapy, or Cognitive Behavioral Therapy (CBT). One positive aspect about these therapies is that they can be administered face-to-face as well as delivered via internet or smartphone. Smartphones are especially helpful as they are highly personalized devices, and offer a well-established ecosystem of apps, accessible via respective marketplaces of differing mobile platforms. Note that current therapeutic treatments such as CBT have shown to be effective in suppressing the tinnitus symptoms when administered face-to-face, their effectiveness when being delivered using smartphones is not known so far. A quick search on the prominent market places of popular mobile platforms (Android and iOS) yielded roughly 250 smartphone apps offering tinnitus-related therapies and tinnitus management. As this number is expected to steadily increase due to high interest in smartphone app development, a contemporary review of such apps is crucial. In this paper, we aim to review scientific studies validating the smartphone apps, particularly to test their effectiveness in tinnitus management and treatment. We use the PRISMA guidelines for identification of studies on major scientific literature sources and delineate the outcomes of identified studies. Full article