Brain Sci., Volume 8, Issue 9 (September 2018) – 19 articles

Regeneration refers to regrowth of tissue in the central nervous system. It includes generation of new neurons, glia, myelin, and synapses, as well as the regaining of essential functions: sensory, motor, emotional and cognitive abilities. Unfortunately, regeneration within the nervous system is very slow compared to other body systems. This relative slowness is attributed to increased vulnerability to irreversible cellular insults and the loss of function due to the very long lifespan of neurons, the stretch of cells and cytoplasm over several dozens of inches throughout the body, insufficiency of the tissue-level waste removal system, and minimal neural cell proliferation/self-renewal capacity. In this context, the current review summarized the most common features of major neurodegenerative disorders; their causes and consequences and proposed novel therapeutic approaches. Full article

Background: Minorities’ Diminished Return (MDR) can be defined as smaller health gains from socioeconomic status (SES) indicators, such as education attainment among ethnic minorities compared to the majority group. The current study tested whether income explains why Black and White adults differ in the association between education attainment and self-rated health (SRH). Methods: With a cross-sectional design, this study used data from Cycle 5 of the Health Information National Trends Survey (HINTS), 2017. With a nationally representative sample, the HINTS study generates results that are generalizable to US adults. This study included 2277 adults who were either non-Hispanic White (n = 1868; 82%) or non-Hispanic Black (n = 409; 18%). The independent variable was education attainment. The dependent variable was SRH, measured using a standard single item. Age, gender, and health insurance status were covariates. Ethnicity was the focal moderator. Income was the mediator. A structural equation model (SEM) was applied for data analysis. Results: Overall, higher education attainment was associated with better SRH, net of covariates. However, a significant interaction between ethnicity and education attainment suggested a smaller SRH gain from education for Blacks compared to Whites. This interaction could be explained by Black–White differences in income. Conclusion: Our study results suggests that labor market preferences may explain smaller effects of education attainment on SRH for Blacks relative to Whites. Given this finding and other studies documenting MDR, policies should reduce labor market discrimination, increasing job opportunities and reducing the racial pay gap for Blacks. Programs should help Blacks compete for prestigious and high-paying jobs. Full article

Repetitive excessive alcohol intoxication leads to neuronal damage and brain shrinkage. We examined cytoskeletal protein expression in human post-mortem tissue from Brodmann’s area 9 of the prefrontal cortex (PFC). Brain samples from 44 individuals were divided into equal groups of 11 control, 11 alcoholic, 11 non-alcoholic suicides, and 11 suicide alcoholics matched for age, sex, and post-mortem delay. Tissue from alcoholic cohorts displayed significantly reduced expression of α- and β-tubulins, and increased levels of acetylated α-tubulin. Protein levels of histone deacetylase-6 (HDAC6), and the microtubule-associated proteins MAP-2 and MAP-tau were reduced in alcoholic cohorts, although for MAPs this was not significant. Tubulin gene expressions increased in alcoholic cohorts but not significantly. Brains from rats administered alcohol for 4 weeks also displayed significantly reduced tubulin protein levels and increased α-tubulin acetylation. PFC tissue from control subjects had reduced tubulin protein expression that was most notable from the sixth to the eighth decade of life. Collectively, loss of neuronal tubulin proteins are a hallmark of both chronic alcohol consumption and natural brain ageing. The reduction of cytosolic tubulin proteins could contribute to the brain volumetric losses reported for alcoholic patients and the elderly. Full article

Even though obese individuals often succeed with weight loss, long-term weight loss maintenance remains elusive. Dietary, lifestyle and psychosocial correlates of weight loss maintenance have been researched, yet the nature of maintenance is still poorly understood. Studying the neural processing of weight loss maintainers may provide a much-needed insight towards sustained obesity management. In this narrative review, we evaluate and critically discuss available evidence regarding the food-related neural responses of weight loss maintainers, as opposed to those of obese or lean persons. While research is still ongoing, available data indicate that following weight loss, maintainers exhibit persistent reward related feeling over food, similar to that of obese persons. However, unlike in obese persons, in maintainers, reward-related brain activity appears to be counteracted by subsequently heightened inhibition. These findings suggest that post-dieting, maintainers acquire a certain level of cognitive control which possibly protects them from weight regaining. The prefrontal cortex, as well as the limbic system, encompass key regions of interest for weight loss maintenance, and their contributions to long term successful weight loss should be further explored. Future possibilities and supportive theories are discussed. Full article

A comprehensive review of the literature-to-date on functional magnetic resonance imaging (fMRI) of the spinal cord is presented. Spinal fMRI has been shown, over more than two decades of work, to be a reliable tool for detecting neural activity. We discuss 10 key points regarding the history, development, methods, and applications of spinal fMRI. Animal models have served a key purpose for the development of spinal fMRI protocols and for experimental spinal cord injury studies. Applications of spinal fMRI span from animal models across healthy and patient populations in humans using both task-based and resting-state paradigms. The literature also demonstrates clear trends in study design and acquisition methods, as the majority of studies follow a task-based, block design paradigm, and utilize variations of single-shot fast spin-echo imaging methods. We, therefore, discuss the similarities and differences of these to resting-state fMRI and gradient-echo EPI protocols. Although it is newly emerging, complex connectivity and network analysis is not only possible, but has also been shown to be reliable and reproducible in the spinal cord for both task-based and resting-state studies. Despite the technical challenges associated with spinal fMRI, this review identifies reliable solutions that have been developed to overcome these challenges. Full article

Reading is essentially a two-channel function, requiring the integration of intact visual and auditory processes both peripheral and central. It is essential for normal reading that these component processes go forward automatically. Based on this model, Boder described three main subtypes of dyslexia: dysphonetic dyslexia (DD), dyseidetic, mixed and besides a fourth group defined non-specific reading delay (NSRD). The subtypes are identified by an algorithm that considers the reading quotient and the % of errors in the spelling test. Chiarenza and Bindelli have developed the Direct Test of Reading and Spelling (DTRS), a computerized, modified and validated version to the Italian language of the Boder test. The sample consisted of 169 subjects with DD and 36 children with NSRD. The diagnosis of dyslexia was made according to the DSM-V criteria. The DTRS was used to identify the dyslexia subtypes and the NSRD group. 2–5 min of artefact-free EEG (electroencephalogram), recorded at rest with eyes closed, according to 10–20 system were analyzed. Stability based Biomarkers identification methodology was applied to the DTRS and the quantitative EEG (QEEG). The reading quotients and the errors of the reading and spelling test were significantly different in the two groups. The DD group had significantly higher activity in delta and theta bands compared to NSRD group in the frontal, central and parietal areas bilaterally. The classification equation for the QEEG, both at the scalp and the sources levels, obtained an area under the robust Receiver Operating Curve (ROC) of 0.73. However, we obtained a discrimination equation for the DTRS items which did not participate in the Boder classification algorithm, with a specificity and sensitivity of 0.94 to discriminate DD from NSRD. These results demonstrate for the first time the existence of different neuropsychological and neurophysiological patterns between children with DD and children with NSRD. They may also provide clinicians and therapists warning signals deriving from the anamnesis and the results of the DTRS that should lead to an earlier diagnosis of reading delay, which is usually very late diagnosed and therefore, untreated until the secondary school level. Full article

Literature on children with Klinefelter Syndrome (KS) points to general linguistic difficulties in both comprehension and production among other cognitive functions, and in the majority of cases, these coexist with an intellectual level within the norms. In these conditions, children having language delay generally engage in language therapy and are systematically monitored across ages. In this article, we present the profiles of two children with KS (47, XXY), aged 9.1 (Child S) and 13 (Child D), whose language development was assessed as adequate at age 3, and for this reason, did not receive any language treatment. At the present stage, their IQ, as measured by Wechsler Scales (Child S: 92; Child D: 101), is within the norm, but they both present marked weaknesses in pragmatic skills such as figurative language comprehension. The analysis of these two cases points to the need to go beyond global indexes of verbal abilities, as the same global index may mask a wide diversification of individual profiles. In addition, this study underlines the importance of monitoring the developmental trajectories of children like Child D and Child S, because weaknesses in pragmatic skills that are relevant for both academic achievement and social adaptation could emerge at later stages. Full article

Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses. Full article

Musical aptitude and language talent are highly intertwined when it comes to phonetic language ability. Research on pre-school children’s musical abilities and foreign language abilities are rare but give further insights into the relationship between language and musical aptitude. We tested pre-school children’s abilities to imitate unknown languages, to remember strings of digits, to sing, to discriminate musical statements and their intrinsic (spontaneous) singing behavior (“singing-lovers versus singing nerds”). The findings revealed that having an ear for music is linked to phonetic language abilities. The results of this investigation show that a working memory capacity and phonetic aptitude are linked to high musical perception and production ability already at around the age of 5. This suggests that music and (foreign) language learning capacity may be linked from childhood on. Furthermore, the findings put emphasis on the possibility that early developed abilities may be responsible for individual differences in both linguistic and musical performances. Full article

Background: Past studies have evaluated the association of various comorbidities with bipolar disorder. This study analyzes differences in the prevalence and association of medical and psychiatric comorbidities in bipolar patients by gender. Methods: A retrospective analysis was conducted using the Nationwide Inpatient Sample (2010–2014). Using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes, we narrowed the study population to comprise those with a primary diagnosis of bipolar disorder and then obtained information about comorbidities. The differences in comorbidities by gender were quantified using chi-square tests and the logistic regression model (odds ratio (OR)). Results: Hypertension (20.5%), asthma (12.5%) and hypothyroidism (8.1%) were the top medical comorbidities found in bipolar patients. Migraine and hypothyroidism were seen three times higher in females (OR = 3.074 and OR = 3.001; respectively). Females with bipolar disorder had higher odds of comorbid inflammatory disorders like asthma (OR = 1.755), Crohn’s disease (OR = 1.197) and multiple sclerosis (OR = 2.440) compared to males. Females had a two-fold higher likelihood of comorbid post-traumatic stress disorder (PTSD) (OR = 2.253) followed by personality disorders (OR = 1.692) and anxiety disorders (OR = 1.663) compared to males. Conclusion: Women with bipolar disorder have a much higher medical comorbidity burden than men and may highly benefit from an integrated team of physicians to manage their condition and improve their health-related quality of life. Full article

We searched for drugs that alleviate the reduction of dopaminergic neurons caused by the administration of lipopolysaccharide (LPS) to the substantia nigra of the rat brain. Human milk fat globule-EGF factor 8 protein (MFG-E8) is similar to MFG-E8-S, a short isoform, of the mouse MFG-E8. However, the function of MFG-E8-S was not clear. Rats with LPS-induced Parkinson’s disease were prepared and the effects of human MFG-E8 were examined. MFG-E8 improved the significant reduction in mesencephalic dopamine neurons induced by the administration of LPS. LPS was administered to human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons to induce inflammation and the effect of MFG-E8 was examined. MFG-E8 showed no toxicity toward neurons. We reanalyzed the results using public microarray data. MFG-E8 mRNA was found to be expressed in all parts of the body, particularly by adipose-derived stem cells (ADSCs). Furthermore, we investigated the culture supernatant of ADSCs using the liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis method and successfully identified the peptide of the MFG-E8 F5/8 type C domain. The results suggested that MFG-E8-S may have a preventive effect against Parkinson’s disease. Full article

Several researchers have proposed a new application for human augmentation, which is to provide human supervision to autonomous artificial intelligence (AI) systems. In this paper, we introduce a framework to implement this proposal, which consists of using Brain–Computer Interfaces (BCI) to influence AI computation via some of their core algorithmic components, such as heuristic search. Our framework is based on a joint analysis of philosophical proposals characterising the behaviour of autonomous AI systems and recent research in cognitive neuroscience that support the design of appropriate BCI. Our framework is defined as a motivational approach, which, on the AI side, influences the shape of the solution produced by heuristic search using a BCI motivational signal reflecting the user’s disposition towards the anticipated result. The actual mapping is based on a measure of prefrontal asymmetry, which is translated into a non-admissible variant of the heuristic function. Finally, we discuss results from a proof-of-concept experiment using functional near-infrared spectroscopy (fNIRS) to capture prefrontal asymmetry and control the progression of AI computation of traditional heuristic search problems. Full article

Previous research has delineated the networks of brain structures involved in the perception of emotional auditory stimuli. These include the amygdala, insula, and auditory cortices, as well as frontal-lobe, basal ganglia, and cerebellar structures involved in the planning and execution of motoric behaviors. The aim of the current research was to examine whether emotional sounds also influence activity in the brainstem and cervical spinal cord. Seventeen undergraduate participants completed a spinal functional magnetic resonance imaging (fMRI) study consisting of two fMRI runs. One run consisted of three one-minute blocks of aversive sounds taken from the International Affective Digitized Sounds (IADS) stimulus set; these blocks were interleaved by 40-s rest periods. The other block consisted of emotionally neutral stimuli also drawn from the IADS. The results indicated a stark pattern of lateralization. Aversive sounds elicited greater activity than neutral sounds in the right midbrain and brainstem, and in right dorsal and ventral regions of the cervical spinal cord. Neutral stimuli, on the other hand, elicited less neural activity than aversive sounds overall; these responses were left lateralized and were found in the medial midbrain and the dorsal sensory regions of the cervical spinal cord. Together, these results demonstrate that aversive auditory stimuli elicit increased sensorimotor responses in brainstem and cervical spinal cord structures. Full article

The aim of this study was to investigate the effect of gait training with bilateral rhythmic auditory stimulation (RAS) on lower extremity rehabilitation in stroke patients. Forty-four participants (<6 months after stroke) were randomly allocated to the gait training with bilateral rhythmic auditory stimulation (GTBR) group (n = 23) and the control group (n = 21). The GTBR group had gait training with bilateral RAS for 30 min a day, 5 days a week, in a 6-week period, in addition to conventional therapy. The control group had gait training without RAS, and conventional therapy. Outcome measures included gait symmetry, gait ability, balance ability, and lower extremity function. Gait symmetry on step time showed significant improvements compared to baseline (p < 0.05) in the GTBR group, but not in the control group. Gait ability was significantly improved in both groups relative to baseline values (p < 0.05), and the GTBR group showed significantly greater improvement in comparison to the control group (p < 0.05). Both groups showed significant improvements in the Timed Up and Go test (TUG), Berg Balance Scale (BBS), and Fugl–Meyer Assessment (FMA) compared to baseline (p < 0.05). GTBR is an effective therapeutic method of improving symmetric gait in stroke rehabilitation. Moreover, we found that GTBR beat frequency matching fast step time might be even more beneficial in improving gait symmetry. Future studies may develop a method of applying RAS on step time and length for improvement of gait symmetry in stroke patients. Full article

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided. Full article

One of the most commonly known chronic neurodegenerative disorders, Alzheimer’s disease (AD), manifests the common type of dementia in 60–80% of cases. From a clinical standpoint, a patent cognitive decline and a severe change in personality, as caused by a loss of neurons, is usually evident in AD with about 50 million people affected in 2016. The disease progression in patients is distinguished by a gradual plummet in cognitive functions, eliciting symptoms such as memory loss, and eventually requiring full-time medical care. From a histopathological standpoint, the defining characteristics are intracellular aggregations of hyper-phosphorylated tau protein, known as neurofibrillary tangles (NFT), and depositions of amyloid β-peptides (Aβ) in the brain. The abnormal phosphorylation of tau protein is attributed to a wide gamut of neurological disorders known as tauopathies. In addition to the hyperphosphorylated tau lesions, neuroinflammatory processes could occur in a sustained manner through astro-glial activation, resulting in the disease progression. Recent findings have suggested a strong interplay between the mechanism of Tau phosphorylation, disruption of microtubules, and synaptic loss and pathology of AD. The mechanisms underlying these interactions along with their respective consequences in Tau pathology are still ill-defined. Thus, in this review: (1) we highlight the interplays existing between Tau pathology and AD; and (2) take a closer look into its role while identifying some promising therapeutic advances including state of the art imaging techniques. Full article

This study is aimed at relating social cognition in Huntington’s Disease (HD) to plasma levels of the social hormone oxytocin (OT). Indeed, HD patients commonly display reduced social skills and OT is involved in bonding behavior and improved recognition of facial emotions. Twelve mild-symptomatic HD patients (stage II Shoulson & Fahn) and 11 gender/age matched controls (healthy controls, HC), without concurrent psychiatric disorders, were investigated at baseline (T₀) for OT plasma levels and social cognition through an extensive battery of neuropsychological tests. Social cognition was also re-examined after two years (T1) in 8 of the 12 patients. Results showed a trend for reduced T₀-OT levels in HD vs. HC, mean ± stardard deviation: 6.5 ± 2.4 vs. 9.9 ± 7.2 pg/mL, without reaching statistical significance. At T₀, patients showed significantly lower performances than controls at the “Faux-Pas” and “Strange Stories” tests (p < 0.05; p < 0.01); a reduced perception of visual emotions (p < 0.01) and verbal stimuli (p < 0.01) was also reported, involving anger, fear, and sadness (p < 0.05; p < 0.01). Additionally, in the HD population, OT concentrations positively correlated with T1-performances at Neutral\Faux-Pas test (p < 0.05), whereas the cognitive Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) scores positively correlated with psychosocial perception at the “Strange Stories” and Karolinska Directed Emotional Faces (KDEF) tests (p < 0.05). This study, despite its limitations, supports correlations between OT and HD social cognition, suggesting a possible therapeutic use of this hormone. More subjects and additional body tissues/fluids, such as cerebrospinal fluid, should be investigated to confirm this hypothesis. Full article

High-density electroencephalography (EEG) was used to examine the utility of the P1 event-related potential (ERP) as a marker of visual motion sensitivity to luminance defined low-spatial frequency drifting gratings in 16 children with autism and 16 neurotypical children. Children with autism displayed enhanced sensitivity to large, high-contrast low-spatial frequency stimuli as indexed by significantly shorter P1 response latencies to large vs. small gratings. The current study also found that children with autism had larger amplitude responses to large gratings irrespective of contrast. A linear regression established that P1 adaptive mean amplitude for large, high-contrast sinusoidal gratings significantly predicted hyperresponsiveness item mean scores on the Sensory Experiences Questionnaire for children with autism, but not for neurotypical children. We conclude that children with autism have differences in the mechanisms that underlie low-level visual processing potentially related to altered visual spatial suppression or contrast gain control. Full article

Background: Cervical dystonia (CD) patients have impaired working memory, processing speed and visual-motor integration ability. We used magnetoencephalography (MEG) to investigate changes in cerebral oscillations in CD patients during an executive function test, before and after administration of botulinum toxin. Methods: MEG data were collected from five CD patients while they performed a visual continuous performance task (CPT), before and after they received a botulinum toxin injection. MEG data was also collected on five controls matched for age and gender. Coherence source imaging was performed to quantify network connectivity of subjects. Results: Controls demonstrated two errors with visual CPT; CD patients demonstrated six and three errors pre- and post-botulinum toxin respectively. After botulinum toxin, mean time from cue to correct response was 0.337 s in controls, 0.390 s in patients before botulinum toxin injection, and 0.366 s after the injection. Differences in coherence between controls and patients were found in the following brain regions: Fronto-frontal, fronto-parietal, fronto-striatal, fronto-occipital, parieto-parietal and temporo-parietal. Intrahemispheric and interhemispheric networks were affected. Post injection, there was minimal change in coherence in the above-mentioned networks. Discussion: Neuropsychological testing suggests difference in coherence in frontal circuits between CD cases and controls during the visual CPT, which may reflect subjects’ increased difficulty with the task. Botulinum toxin is associated with minimal improvement with executive function in CD. Full article