Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.

Synergistic effect of polymorphism, substrate conductivity and electric field stimulation towards enhancing muscle cell growth in vitro

Poly(vinylidene difluoride), a well-known candidate for artificial muscle patch applications is a semi-crystalline polymer with a host of attributes such as piezo- and pyroelectricity, polymorphism along with low dielectric constant and stiffness. The present work explores the unique interplay among the factors (conductivity, polymorphism and electrical stimulation) towards cell proliferation on poly(vinylidene difluoride) (PVDF)-based composites. In this regard, multi-walled carbon nanotubes (MWNTs) are introduced in the PVDF matrix (limited to 2%) through melt mixing to increase the conductivity of PVDF. The addition of MWNTs also led to an increase in the fraction of piezoelectric beta-phase, tensile strength and modulus. The melting and crystallization behaviour of PVDF-MWNT together with FT-IR confirms that the crystallization is found to be aided by the presence of MWNT. The conducting PVDF-MWNTs are used as substrates for the growth of C2C12 mouse myoblast cells and electrical stimulation with a range of field strengths (0-2 V cm(-1)) is intermittently delivered to the cells in culture. The cell viability results suggest that metabolically active cell numbers can statistically increase with electric stimulation up to 1 V cm(-1), only on the PVDF + 2% MWNT. Summarising, the current study highlights the importance of biophysical cues on cellular function at the cell-substrate interface. This study further opens up new avenues in designing conducting substrates, that can be utilized for enhancing cell viability and proliferation and also reconfirms the lack of toxicity of MWNTs, when added in a tailored manner.

Comparison of Matching Pursuit Algorithm with Other Signal Processing Techniques for Computation of the Time-Frequency Power Spectrum of Brain Signals

Signals recorded from the brain often show rhythmic patterns at different frequencies, which are tightly coupled to the external stimuli as well as the internal state of the subject. In addition, these signals have very transient structures related to spiking or sudden onset of a stimulus, which have durations not exceeding tens of milliseconds. Further, brain signals are highly nonstationary because both behavioral state and external stimuli can change on a short time scale. It is therefore essential to study brain signals using techniques that can represent both rhythmic and transient components of the signal, something not always possible using standard signal processing techniques such as short time fourier transform, multitaper method, wavelet transform, or Hilbert transform. In this review, we describe a multiscale decomposition technique based on an over-complete dictionary called matching pursuit (MP), and show that it is able to capture both a sharp stimulus-onset transient and a sustained gamma rhythm in local field potential recorded from the primary visual cortex. We compare the performance of MP with other techniques and discuss its advantages and limitations. Data and codes for generating all time-frequency power spectra are provided.

First human hNT neurons patterned on parylene-C/silicon dioxide substrates: Combining an accessible cell line and robust patterning technology for the study of the pathological adult human brain

In this communication, we describe a new method which has enabled the first patterning of human neurons (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/silicon dioxide substrates. We reveal the details of the nanofabrication processes, cell differentiation and culturing protocols necessary to successfully pattern hNT neurons which are each key aspects of this new method. The benefits in patterning human neurons on silicon chip using an accessible cell line and robust patterning technology are of widespread value. Thus, using a combined technology such as this will facilitate the detailed study of the pathological human brain at both the single cell and network level. © 2010 Elsevier B.V.

GFAP Isoforms in Adult Mouse Brain with a Focus on Neurogenic Astrocytes and Reactive Astrogliosis in Mouse Models of Alzheimer Disease

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Plasma brain-derived neurotrophic factor levels, learning capacity and cognition in patients with first episode psychosis

Background: Cognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls. Methods: 45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment. Results: Plasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability,immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores. Conclusion: Our results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.

Stock Composition of Some Sockeye Salmon, Oncorhynchus nerka, Catches in Southeast Alaska, Based on Incidence of Allozyme Variants, Freshwater Ages, and a Brain-Tissue Parasite

The incidence of four discrete characters of individual sockeye salmon -two genetically inherited proteins (PGM-1*and PGM-2*), freshwater age at migration, and the presence of the brain-tissue parasite Myxobolus arcticus-in weekly samples from two Alaskan fisheries (Noyes Island in 1986 and Sumner Strait in 1987) were used to infer stock composition of the catches based on corresponding character samples from 73 Alaskan and Canadian stocks. Estimated contributions of 13 stock groups, formed on the basis of character similarity of their members, were roughly consistent with expectations from tagging experiments, knowledge of stock magnitudes, and similar assessments from scales. Imprecision of the estimated contributions by the 13 stock groups limited their practical value; but variability was much reduced for combined estimated contributions by two inclusive categories, namely stock groups whose members had either high or low brainparasite prevalence. Noyes Island catches consisted predominantly of unparasitized fish, most of which were probably of Canadian origin. The majority of Sumner Strait catches consisted of parasitized fish, whose freshwater origins may have been in Alaska or Canada. (PDF file contains 27 pages.)

Behavioral, neurochemical and morphological changes induced by the overexpression of munc18-1a in brain of mice: relevance to schizophrenia

Overexpression of the mammalian homolog of the unc-18 gene (munc18-1) has been described in the brain of subjects with schizophrenia. Munc18-1 protein is involved in membrane fusion processes, exocytosis and neurotransmitter release. A transgenic mouse strain that overexpresses the protein isoform munc18-1a in the brain was characterized. This animal displays several schizophrenia-related behaviors, supersensitivity to hallucinogenic drugs and deficits in prepulse inhibition that reverse after antipsychotic treatment. Relevant brain areas (that is, cortex and striatum) exhibit reduced expression of dopamine D-1 receptors and dopamine transporters together with enhanced amphetamine-induced in vivo dopamine release. Magnetic resonance imaging demonstrates decreased gray matter volume in the transgenic animal. In conclusion, the mouse overexpressing brain munc18-1a represents a new valid animal model that resembles functional and structural abnormalities in patients with schizophrenia.

Role of G protein coupled inwardly rectifier K+ channels (GIRK) on the neurobiology depression

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The interactive brain hypothesis

Enactive approaches foreground the role of interpersonal interaction in explanations of social understanding. This motivates, in combination with a recent interest in neuroscientific studies involving actual interactions, the question of how interactive processes relate to neural mechanisms involved in social understanding. We introduce the Interactive Brain Hypothesis (IBH) in order to help map the spectrum of possible relations between social interaction and neural processes. The hypothesis states that interactive experience and skills play enabling roles in both the development and current function of social brain mechanisms, even in cases where social understanding happens in the absence of immediate interaction. We examine the plausibility of this hypothesis against developmental and neurobiological evidence and contrast it with the widespread assumption that mindreading is crucial to all social cognition. We describe the elements of social interaction that bear most directly on this hypothesis and discuss the empirical possibilities open to social neuroscience. We propose that the link between coordination dynamics and social understanding can be best grasped by studying transitions between states of coordination. These transitions form part of the self-organization of interaction processes that characterize the dynamics of social engagement. The patterns and synergies of this self-organization help explain how individuals understand each other. Various possibilities for role-taking emerge during interaction, determining a spectrum of participation. This view contrasts sharply with the observational stance that has guided research in social neuroscience until recently. We also introduce the concept of readiness to interact to describe the practices and dispositions that are summoned in situations of social significance (even if not interactive). This latter idea links interactive factors to more classical observational scenarios.