A practical application of text mining to literature on cognitive rehabilitation and enhancement through neurostimulation

The exponential growth in publications represents a major challenge for researchers. Many scientific domains, including neuroscience, are not yet fully engaged in exploiting large bodies of publications. In this paper, we promote the idea to partially automate the processing of scientific documents, specifically using text mining (TM), to efficiently review big corpora of publications. The “cognitive advantage” given by TM is mainly related to the automatic extraction of relevant trends from corpora of literature, otherwise impossible to analyze in short periods of time. Specifically, the benefits of TM are increased speed, quality and reproducibility of text processing, boosted by rapid updates of the results. First, we selected a set of TM-tools that allow user-friendly approaches of the scientific literature, and which could serve as a guide for researchers willing to incorporate TM in their work. Second, we used these TM-tools to obtain basic insights into the relevant literature on cognitive rehabilitation (CR) and cognitive enhancement (CE) using transcranial magnetic stimulation (TMS). TM readily extracted the diversity of TMS applications in CR and CE from vast corpora of publications, automatically retrieving trends already described in published reviews. TMS emerged as one of the important non-invasive tools that can both improve cognitive and motor functions in numerous neurological diseases and induce modulations/enhancements of many fundamental brain functions. TM also revealed trends in big corpora of publications by extracting occurrence frequency and relationships of particular subtopics. Moreover, we showed that CR and CE share research topics, both aiming to increase the brain's capacity to process information, thus supporting their integration in a larger perspective. Methodologically, despite limitations of a simple user-friendly approach, TM served well the reviewing process

The sensory-motor rehabilitation of tetraplegics via neuromuscular electrical stimulation

O objetivo desta pesquisa consiste em verificar o ganho neurológico e a independência na execução de atividades funcionais em tetraplégicos durante o período de 6 meses de reabilitação com Estimulação Elétrica Neuro-Muscular (EENM). Foram realizados, em oito pacientes do sexo masculino, os Protocolos ASIA e FIM no período pré e pós tratamento que consistiu na Estimulação de membros inferiores e superiores, com realização de Atividades funcionais a partir da restauração de preensões. Os dados desta pesquisa foram analisados por meio de estudos de caso devido a variabilidade intersujeitos. Os tetraplégicos foram capazes de realizar todas as Atividades propostas, o que sem a EENM não seria possível. A recuperação sensório-motora foi maior nos membros superiores comparado aos membros inferiores. A maioria dos pacientes apresentou ganho neurológico com conseqüente diminuição do nível de lesão, bem como, aumento no índice de independência funcional. Portanto, estes efeitos terapêuticos da reabilitação através de EENM indicam plasticidade neural.The objective of this research was to evaluate the independence to perform activities of daily living and neurological improvements due to a period of six months of Neuromuscular Electrical Stimulation (NMES). Eight tetraplegics participated in this study. The evaluations were accomplished with the ASIA and FIM Protocols. The treatment consisted in lower and upper limbs stimulation (prehension restauration). The results of this research was analised by case reports due the intersubject variability. The tetraplegics were able to perform all activities, wich without NMES was impossible to do. The sensory-motor recovery was higher in the upper limbs compared with lower limbs. The most patients showed neurological improvements and also in the index of functional independence due to the therapeutic effects of NMES

Does the Brain Function as a Quantum Phase Computer Using Phase Ternary Computation?

Here we provide evidence that the fundamental basis of nervous communication is derived from a pressure pulse/soliton capable of computation with sufficient temporal precision to overcome any processing errors. Signalling and computing within the nervous system are complex and different phenomena. Action potentials are plastic and this makes the action potential peak an inappropriate fixed point for neural computation, but the action potential threshold is suitable for this purpose. Furthermore, neural models timed by spiking neurons operate below the rate necessary to overcome processing error. Using retinal processing as our example, we demonstrate that the contemporary theory of nerve conduction based on cable theory is inappropriate to account for the short computational time necessary for the full functioning of the retina and by implication the rest of the brain. Moreover, cable theory cannot be instrumental in the propagation of the action potential because at the activation-threshold there is insufficient charge at the activation site for successive ion channels to be electrostatically opened. Deconstruction of the brain neural network suggests that it is a member of a group of Quantum phase computers of which the Turing machine is the simplest: the brain is another based upon phase ternary computation. However, attempts to use Turing based mechanisms cannot resolve the coding of the retina or the computation of intelligence, as the technology of Turing based computers is fundamentally different. We demonstrate that that coding in the brain neural network is quantum based, where the quanta have a temporal variable and a phase-base variable enabling phase ternary computation as previously demonstrated in the retina.Comment: 16 pages, 7 figures. Key Words: Plasticity; Action potential; Timing; Error redaction; Synchronization; Quantum phase computation; Phase ternary computation; Retinal mode

A Comparative Study of Cell Specific Effects of Systemic and Volatile Anesthetics on Identified Motor Neurons and Interneurons of Lymnaea stagnalis (L.), Both in the Isolated Brain and in Single Cell Culture

1. A comparative descriptive analysis of systemic (sodium pentobarbital, sodium thiopentone, ketamine) and volatile (halothane, isoflurane, enflurane) general anesthetics revealed important differences in the neuronal responses of identified motor neurons and interneurons in the isolated central nervous system (CNS) and cultured identified neurons in single cell culture of Lymnaea stagnalis (L.).2. At high enough concentrations all anesthetics eventually caused cessation of spontaneous or evoked action potentials, but volatile anesthetics were much faster acting. Halothane at low concentrations caused excitation, thought to be equivalent to the early excitatory phase of anesthesia. Strong synaptic inputs were not always abolished by pentobarbital.3. There were cell specific concentration-dependent responses to halothane and pentobarbital in terms of membrane potential, action potential characteristics, the after hyperpolarization and patterned activity. Individual neurons generated specific responses to the applied anesthetics.4. The inhalation anesthetics, enflurane, and isoflurane, showed little concentration dependence of effect, in contrast to results obtained with halothane. Enflurane was faster acting than halothane and isoflurane was particularly different, producing quiescence in all cells types studied at all concentrations studied.5. Halothane, enflurane, the barbiturate general anesthetics, pentobarbital, and sodium thiopentone and the dissociative anesthetic ketamine, produced two distinctly different effects which could be correlated with cell type and their location in the isolated brain: either a decline in spontaneous and evoked activity prior to quiescence in interneurons or paroxysmal depolarizing shifts (PDS) in motor neurons, again prior to quiescence, which were reversed when the anesthetic was eliminated from the bath. In the strongly electrically coupled motor neurons, VD1 and RPD2, both types of response were observed, depending on the anesthetic used. Thus, with the exception isoflurane, all the motor neurons subjected to the anesthetic agents studied here were capable of generating PDS in situ, but the interneurons did not do so.6. The effects of halothane on isolated cultured neurons indicates that PDS can be generated by single identified neurons in the absence of synaptic inputs. Further, many instances of PDS in neurons that do not generate it in situ have been found in cultured neurons. The nature of PDS is discussed

Brain Training and Meditation’s Effects on Memory in Subjects with Vascular Cognitive Impairment

Vascular Dementia (VaD) is an important public health concern, which causes significant morbidity and mortality amongst populations around the world. With the increases in average age of individuals and prevalence of cardiovascular risk factors, the incidence of vascular cognitive impairment (VCI) and VaD are on the rise. Most of this increase will come from cerebral small vessel disease (CSVD) as treatment for large vessel disease improves. Yet, very few interventions are recommended for CSVD beyond control of risk factors. In this thesis, we propose a non-pharmacological intervention, which we believe may address executive dysfunction in VCI due to CSVD. CSVD impairs functional frontal-subcortical connectivity and results in cognitive and functional impairments. Given the plasticity in these circuits, despite old age, cognitive training may be a good candidate for improving cognition in CSVD. However, previous studies have suffered from heterogeneity of pathologies in VCI by including both large and small vessel disease. Furthermore, they have often not considered the effects of anxiety and depression, which we aim to exclude from the study. Finally, these studies do not use validated composite scores as a primary endpoint and currently do not use any biomarkers to follow the progress of subjects. In this study, we aim to partially address these shortcomings and offer a more rigorous approach to cognitive training

Signaling Mechanisms Regulating Neuronal Growth Cone Dynamics

During the development of the nervous system, neurons migrate to their final location and extend neurites that navigate long distances in the extracellular environment to reach their synaptic targets. The proper functioning of the nervous system depends on correct connectivity, and mistakes in the wiring of the nervous system lead to brain abnormalities and mental illness. Growth cones are motile structures located at the tip of extending neurites that sense and respond to guidance cues encountered along the path toward their targets. Binding of these cues to receptors located on growth cone filopodia and lamellipodia triggers intracellular signaling pathways that regulate growth cone cytoskeletal dynamics. Although studies on extracellular cues and their effects on neuronal guidance are well documented, less is known about the intracellular signaling mechanisms that regulate growth cone motility. This dissertation focuses on two signaling pathways and describes how they might be involved in determining growth cone morphology during neuronal development. The specific aims of this work address: (1) the role of phosphatidylinositol-3-kinase (PI-3K) and its downstream signaling pathway in regulating growth cone motility, and (2) the effect of nitric oxide (NO) release from a single cell on growth cone morphology of neighboring neurons. This study employs defined neurons from the pond snail, Helisoma trivolvis, to demonstrate that inhibition of PI-3K induces a concomitant increase in filopodial length and a decrease in the rate at which neurites advance. These effects are mediated through the lipid and protein kinase activities of PI-3K, and filopodial elongation is due to an increase in the rate at which filopodia elongate and the time that individual filopodia spend extending. Additionally, this study demonstrates that NO release from a single cell can affect growth cone dynamics on neighboring neurons via soluble guanylyl cyclase (sGC), and that NO has a physiological effect up to a distance of 100 ìm. Overall this study provides new information on cellular mechanisms regulating growth cone motility, and suggests a potential role of PI-3K and NO in neuronal pathfinding in vivo

Neuronal Growth Cone Dynamics are Regulated by a Nitric Oxide-Initiated Second Messenger Pathway.

During development, neurons must find their way to and make connections with their appropriate targets. Growth cones are dynamic, motile structures that are integral to the establishment of appropriate connectivity during this wiring process. As growth cones migrate through their environment, they encounter guidance cues that direct their migration to their appropriate synaptic targets. The gaseous messenger nitric oxide (NO), which diffuses across the plasma membrane to act on intracellular targets, is a signaling molecule that affects growth cone motility. However, most studies have examined the effects of NO on growth cone morphology when applied in large concentrations and to entire cells. In addition, the intracellular second messenger cascade activated by NO to bring about these changes in growth cone morphology is not well understood. Therefore, this dissertation addresses the effects that a spatially- and temporally-restricted application of physiological amounts of NO can have on individual growth cone morphology, on the second messenger pathway that is activated by this application of NO, and on the calcium cascades that result and ultimately affect growth cone morphology. Helisoma trivolvis, a pond snail, is an excellent model system for this type of research because it has a well-defined nervous system and cultured neurons form large growth cones. In the present study, local application of NO to Helisoma trivolvis B5 neurons results in an increase in filopodial length, a decrease in filopodial number, and an increase in the intracellular calcium concentration ([Ca2+]i). In B5 neurons, the effects of NO on growth cone behavior and [Ca2+]i are mediated via sGC, protein kinase G, cyclic adenosine diphosphate ribose, and ryanodine receptor-mediated intracellular calcium release. This study demonstrates that neuronal growth cone pathfinding in vitro is affected by a single spatially- and temporally-restricted exposure to NO. Furthermore, NO acts via a second messenger cascade, resulting in a calcium increase that leads to cytoskeletal changes. These results suggest that NO may be a signal that promotes appropriate pathfinding and/or target recognition within the developing nervous system. Taken together, these data indicate that NO may be an important messenger during the development of the nervous system in vivo

Sense and Insensibility – An Appraisal of the Effects of Clinical Anesthetics on Gastropod and Cephalopod Molluscs as a Step to Improved Welfare of Cephalopods

Recent progress in animal welfare legislation stresses the need to treat cephalopod molluscs, such as Octopus vulgaris, humanely, to have regard for their wellbeing and to reduce their pain and suffering resulting from experimental procedures. Thus, appropriate measures for their sedation and analgesia are being introduced. Clinical anesthetics are renowned for their ability to produce unconsciousness in vertebrate species, but their exact mechanisms of action still elude investigators. In vertebrates it can prove difficult to specify the differences of response of particular neuron types given the multiplicity of neurons in the CNS. However, gastropod molluscs such as Aplysia, Lymnaea, or Helix, with their large uniquely identifiable nerve cells, make studies on the cellular, subcellular, network and behavioral actions of anesthetics much more feasible, particularly as identified cells may also be studied in culture, isolated from the rest of the nervous system. To date, the sorts of study outlined above have never been performed on cephalopods in the same way as on gastropods. However, criteria previously applied to gastropods and vertebrates have proved successful in developing a method for humanely anesthetizing Octopus with clinical doses of isoflurane, i.e., changes in respiratory rate, color pattern and withdrawal responses. However, in the long term, further refinements will be needed, including recordings from the CNS of intact animals in the presence of a variety of different anesthetic agents and their adjuvants. Clues as to their likely responsiveness to other appropriate anesthetic agents and muscle relaxants can be gained from background studies on gastropods such as Lymnaea, given their evolutionary history

Multilingualism and the risk of Alzheimer disease and dementia

Background: Alzheimer disease (AD) is a progressive, late-life neurodegenerative disorder. Given the aging population, AD is a significant health concern. According to the Alzheimer Society of Canada (Smetanin et al., 2009), in 25 years 2.8% of the Canadian population will have AD or a related dementia. Presently, there is no cure for AD; therefore, efforts to either delay AD onset or prevent AD altogether are a primary focus. The ability to proficiently speak many languages has been associated with certain cognitive advantages. Based on these findings, multilinguals are hypothesized to be more resistant to cognitive decline than monolinguals. More research is warranted in order to further this theory and to contribute to strategies to prevent or delay AD. Objectives: The first study objective was to evaluate whether multilingualism was associated with the development of AD. The second study objective was to assess whether multilingualism was associated with later dementia onset. Methods: Analyses were based on data from the Nun Study, a longitudinal study of aging in 678 participants 75+ years living in the United States. In order to address the first study objective, the association between multilingualism and AD was assessed in 157 participants using logistic regression models adjusted for age, education, apolipoprotein E-E4 (ApoE-E4) status, immigrant status, and occupation. Additional subgroup analyses also included covariates associated with career length and linguistic ability (grammatical complexity and idea density). AD was diagnosed based on criteria for both clinical dementia and AD neuropathology. Dementia was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition criterion (American Psychiatric Association, 1994) (based on the Consortium to Establish a Registry for Alzheimer’s Disease battery of tests (Morris, Heyman, Mohs, & Hughes, 1989) and performance on activities of daily living), while AD neuropathology was based on the National Institute on Aging and Reagan Institute criterion (The National Institute on Aging - Reagan Institute (NIA-RI) Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease, 1997). In order to address the second study objective, dementia likelihood was assessed in 325 participants using discrete-time survival analyses adjusted for age, ApoE-E4 status, education, and linguistic ability. Results: When adjusted for age, education, ApoE-E4 status, occupation, and immigrant status, participants speaking two or more languages had similar AD risks compared to monolinguals (OR = 1.05; 95% CI = 0.45-2.50). However, when grammatical complexity was held constant across participants, speaking two or more languages was associated with a four-fold decrease in AD risk compared to speaking one language (OR = 0.25; 95% CI = 0.04-1.23), although this did not reach statistical significance. When the association between multilingualism and time of dementia onset was assessed, the dementia hazard function estimates for all participants were constant and persisted throughout the follow-up period of the study. When ApoE-E4 status and baseline age were held constant, participants speaking four or more languages were significantly less likely to develop dementia than monolingual participants (OR = 0.14; 95% CI = 0.01-0.66). An interaction between multilingualism and the other two covariates (ApoE-E4 status and baseline age) was observed: the oldest participants with an ApoE-E4 allele who spoke four or more languages had smaller dementia risks than younger participants without an ApoE-E4 allele who spoke one, two, or three languages. Participants speaking two or three languages were no less likely than monolinguals to develop dementia across the study duration. When idea density was held constant across participants, multilingualism was associated with a nonsignificant decreased risk of dementia for individuals speaking three (OR = 0.62; 95% CI = 0.16-2.41) or four or more languages (OR = 0.53; 95% CI = 0.06-4.91) while participants speaking two languages were no more at risk for dementia than monolinguals (OR = 1.08; 95% CI = 0.43-2.69). Discussion: Initially, multilingualism did not appear to confer protection against AD. After holding grammatical complexity constant across all participants, however, multilingualism was found to be associated with AD risk. Therefore, linguistic ability confounded the initial relationship measured by this study. When the association between multilingualism and time of dementia onset was evaluated, participants were no more likely to develop dementia in one time period than another, and monolingual participants were no more likely to develop dementia in earlier time periods than multilinguals. While a trend of decreasing dementia risk with ascending number of languages spoken was not observed, speaking four or more languages was consistently associated with decreased dementia risk compared to speaking one language. The presence of an ApoE-E4 allele and low linguistic ability had a strong and consistent significant association with increased AD and dementia risk. Therefore, the influence of these variables on the association of multilingualism with AD and dementia is worthy of further exploration. Overall, this study provided some support for a protective effect of multilingualism on AD and dementia. Some of the present investigation’s results differ, however, from those of previous studies. This is not surprising, considering the present study utilized different methodologies than other studies in this research area. For instance, our study employed a definition of multilingualism based on self-report data – participants were classified as multilingual based on the number of languages they reported proficiency with. Therefore, our definition of multilingualism was less strict than definitions used in previous studies. However, our study employed much stricter outcome criteria than those used in previous studies, as our study is the first in this area to confirm AD cases with AD neuropathology evaluations. Our study is also the first io utilize prospective data and to include participants who remained dementia-free in addition to participants developing AD and dementia. In addition, this is the only study in this research area to evaluate the relationship of multilingualism with AD and dementia in the context of important covariates such as ApoE-E4 status and linguistic ability. Therefore, while some of our results contrast with other findings in this area, this is understandable given our novel methodologies. A broad range of study methods must be used in the future if we are to generate the depth of evidence needed for a full understanding of the relationship of multilingualism with AD and dementia. A better understanding of this relationship may also provide insight into both cognitive and brain reserve mechanisms, which could help more individuals maintain cognitive function into late life