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Sample records for cultured primary motor

  1. Contrasting effects of cerebrospinal fluid from motor neuron disease patients on the survival of primary motor neurons cultured with or without glia.

    PubMed

    Barber, Siân C; Wood-Allum, Clare A; Sargsyan, Siranush A; Walsh, Theresa; Cox, Laura E; Monk, Peter N; Shaw, Pamela J

    2011-07-01

    Motor neuronal (MN) degeneration in motor neuron disease (MND) often starts focally before spreading to neighbouring MN populations, suggesting soluble factors may contribute to disease propagation. Whether cerebrospinal fluid (CSF) from MND patients contains such factors has been difficult to prove. We aimed to determine the effect of glia on the response of MNs to CSF from MND patients. Primary rat spinal MNs grown in mono-culture or cocultured with glia were exposed to CSF from patients (MND-CSF) or controls (Con-CSF) and survival measured by cell counting. In mono-culture both MND-CSF and Con-CSF reduced MN survival with MND-CSF reducing MN survival by less than Con-CSF. In coculture MN survival was unchanged by exposure to MND-CSF while exposure to Con-CSF improved MN survival. In separate experiments, murine MNs grown in mono-culture and stressed by growth factor withdrawal were partially rescued by the application of monocyte chemoattractant protein-1 (MCP-1), a trophic factor previously found to be elevated in MND-CSF. Our results suggest that MND-CSF may contain factors harmful to MNs as well as factors protective of MNs, the interplay of which is altered by the presence of glial cells. These preliminary results further emphasize the importance of MN environment to MN health.

  2. Cultural entrainment of motor skill development: Learning to write hiragana in Japanese primary school

    PubMed Central

    2017-01-01

    Abstract The aim of the present study was to examine how the social norms shared in a classroom environment influence the development of movement dynamics of handwriting of children who participate in the environment. To look into this issue, the following aspects of the entire period of classroom learning of hiragana letters in Japanese 1st graders who had just entered primary school were studied: First, the structure of classroom events and the specific types of interaction and learning within such environment were described. Second, in the experiment involving 6‐year‐old children who participated in the class, writing movements of children and their changes over the period of hiragana education were analyzed for each stroke composing letters. It was found that writing movement of children became differentiated in a manner specific to the different types of stroke endings, to which children were systematically encouraged to attend in the classroom. The results provide a detailed description of the process of how dynamics of fine motor movement of children is modulated by the social norms of a populated, classroom environment in a non‐Latin alphabet writing system. PMID:28608521

  3. Cultural entrainment of motor skill development: Learning to write hiragana in Japanese primary school.

    PubMed

    Nonaka, Tetsushi

    2017-09-01

    The aim of the present study was to examine how the social norms shared in a classroom environment influence the development of movement dynamics of handwriting of children who participate in the environment. To look into this issue, the following aspects of the entire period of classroom learning of hiragana letters in Japanese 1st graders who had just entered primary school were studied: First, the structure of classroom events and the specific types of interaction and learning within such environment were described. Second, in the experiment involving 6-year-old children who participated in the class, writing movements of children and their changes over the period of hiragana education were analyzed for each stroke composing letters. It was found that writing movement of children became differentiated in a manner specific to the different types of stroke endings, to which children were systematically encouraged to attend in the classroom. The results provide a detailed description of the process of how dynamics of fine motor movement of children is modulated by the social norms of a populated, classroom environment in a non-Latin alphabet writing system. © 2017 The Authors. Developmental Psychobiology Published by Wiley Periodicals, Inc.

  4. KIF1A is the primary anterograde motor protein required for the axonal transport of dense-core vesicles in cultured hippocampal neurons.

    PubMed

    Lo, K Y; Kuzmin, A; Unger, S M; Petersen, J D; Silverman, M A

    2011-03-24

    Dense-core vesicles (DCVs) are responsible for transporting, processing, and secreting neuropeptide cargos that mediate a wide range of biological processes, including neuronal development, survival, and learning and memory. DCVs are synthesized in the cell body and are transported by kinesin motor proteins along microtubules to pre- and postsynaptic release sites. Due to the dependence on kinesin-based transport, we sought to determine if the kinesin-3 family member, KIF1A, transports DCVs in primary cultured hippocampal neurons, as has been described for invertebrate neurons. Two-color, live-cell imaging showed that the DCV markers, chromogranin A-RFP and BDNF-RFP, move together with KIF1A-GFP in both the anterograde and retrograde directions. To demonstrate a functional role for KIF1A in DCV transport, motor protein expression in neurons was reduced using RNA interference (shRNA). Fluorescently tagged DCV markers showed a significant reduction in organelle flux in cells expressing shRNA against KIF1A. The transport of cargo driven by motors other than KIF1A, including mitochondria and the transferrin receptor, was unaffected in KIF1A shRNA expressing cells. Taken together, these data support a primary role for KIF1A in the anterograde transport of DCVs in mammalian neurons, and also provide evidence that KIF1A remains associated with DCVs during retrograde DCV transport. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Motor sequence learning and motor adaptation in primary cervical dystonia.

    PubMed

    Katschnig-Winter, Petra; Schwingenschuh, Petra; Davare, Marco; Sadnicka, Anna; Schmidt, Reinhold; Rothwell, John C; Bhatia, Kailash P; Edwards, Mark J

    2014-06-01

    Motor sequence learning and motor adaptation rely on overlapping circuits predominantly involving the basal ganglia and cerebellum. Given the importance of these brain regions to the pathophysiology of primary dystonia, and the previous finding of abnormal motor sequence learning in DYT1 gene carriers, we explored motor sequence learning and motor adaptation in patients with primary cervical dystonia. We recruited 12 patients with cervical dystonia and 11 healthy controls matched for age. Subjects used a joystick to move a cursor from a central starting point to radial targets as fast and accurately as possible. Using this device, we recorded baseline motor performance, motor sequence learning and a visuomotor adaptation task. Patients with cervical dystonia had a significantly higher peak velocity than controls. Baseline performance with random target presentation was otherwise normal. Patients and controls had similar levels of motor sequence learning and motor adaptation. Our patients had significantly higher peak velocity compared to controls, with similar movement times, implying a different performance strategy. The preservation of motor sequence learning in cervical dystonia patients contrasts with the previously observed deficit seen in patients with DYT1 gene mutations, supporting the hypothesis of differing pathophysiology in different forms of primary dystonia. Normal motor adaptation is an interesting finding. With our paradigm we did not find evidence that the previously documented cerebellar abnormalities in cervical dystonia have a behavioral correlate, and thus could be compensatory or reflect "contamination" rather than being directly pathological. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Can Touch Screen Tablets be Used to Assess Cognitive and Motor Skills in Early Years Primary School Children? A Cross-Cultural Study

    PubMed Central

    Pitchford, Nicola J.; Outhwaite, Laura A.

    2016-01-01

    Assessment of cognitive and motor functions is fundamental for developmental and neuropsychological profiling. Assessments are usually conducted on an individual basis, with a trained examiner, using standardized paper and pencil tests, and can take up to an hour or more to complete, depending on the nature of the test. This makes traditional standardized assessments of child development largely unsuitable for use in low-income countries. Touch screen tablets afford the opportunity to assess cognitive functions in groups of participants, with untrained administrators, with precision recording of responses, thus automating the assessment process. In turn, this enables cognitive profiling to be conducted in contexts where access to qualified examiners and standardized assessments are rarely available. As such, touch screen assessments could provide a means of assessing child development in both low- and high-income countries, which would afford cross-cultural comparisons to be made with the same assessment tool. However, before touch screen tablet assessments can be used for cognitive profiling in low-to-high-income countries they need to be shown to provide reliable and valid measures of performance. We report the development of a new touch screen tablet assessment of basic cognitive and motor functions for use with early years primary school children in low- and high-income countries. Measures of spatial intelligence, visual attention, short-term memory, working memory, manual processing speed, and manual coordination are included as well as mathematical knowledge. To investigate if this new touch screen assessment tool can be used for cross-cultural comparisons we administered it to a sample of children (N = 283) spanning standards 1–3 in a low-income country, Malawi, and a smaller sample of children (N = 70) from first year of formal schooling from a high-income country, the UK. Split-half reliability, test-retest reliability, face validity, convergent

  7. Can Touch Screen Tablets be Used to Assess Cognitive and Motor Skills in Early Years Primary School Children? A Cross-Cultural Study.

    PubMed

    Pitchford, Nicola J; Outhwaite, Laura A

    2016-01-01

    Assessment of cognitive and motor functions is fundamental for developmental and neuropsychological profiling. Assessments are usually conducted on an individual basis, with a trained examiner, using standardized paper and pencil tests, and can take up to an hour or more to complete, depending on the nature of the test. This makes traditional standardized assessments of child development largely unsuitable for use in low-income countries. Touch screen tablets afford the opportunity to assess cognitive functions in groups of participants, with untrained administrators, with precision recording of responses, thus automating the assessment process. In turn, this enables cognitive profiling to be conducted in contexts where access to qualified examiners and standardized assessments are rarely available. As such, touch screen assessments could provide a means of assessing child development in both low- and high-income countries, which would afford cross-cultural comparisons to be made with the same assessment tool. However, before touch screen tablet assessments can be used for cognitive profiling in low-to-high-income countries they need to be shown to provide reliable and valid measures of performance. We report the development of a new touch screen tablet assessment of basic cognitive and motor functions for use with early years primary school children in low- and high-income countries. Measures of spatial intelligence, visual attention, short-term memory, working memory, manual processing speed, and manual coordination are included as well as mathematical knowledge. To investigate if this new touch screen assessment tool can be used for cross-cultural comparisons we administered it to a sample of children (N = 283) spanning standards 1-3 in a low-income country, Malawi, and a smaller sample of children (N = 70) from first year of formal schooling from a high-income country, the UK. Split-half reliability, test-retest reliability, face validity, convergent construct

  8. Motor imagery development in primary school children.

    PubMed

    Caeyenberghs, Karen; Tsoupas, Jenny; Wilson, Peter H; Smits-Engelsman, Bouwien C M

    2009-01-01

    Motor imagery provides a unique window on the integrity of movement representation. How this ability unfolds during development remains unknown, however. It was the aim of this cross-sectional study to chart the development of movement imagery over childhood using validated measures, and to examine its relationship to movement skill. A sample of 58 children aged 7-12 years were recruited from Australian primary schools. Motor imagery ability was assessed using the Radial Pointing Task and a (mental) Hand Rotation Task, whereas visual (or object-related) imagery was measured on a Letter Rotation Task. Motor skill was assessed on the McCarron Assessment of Neuromuscular Development (MAND). Results showed clear age differences on all measures: motor skill, motor imagery, and visual imagery. The relationship between motor imagery and motor skill was shown to become stronger with age, whereas no relationship between visual imagery and motor skill was evident at any age. Taken together, these results show that motor imagery has a distinct developmental trajectory that is entwined with the development of movement skill in children. We argue that movement imagery reflects the unfolding of internal modeling processes providing the foundation for adaptive, goal-directed movements.

  9. Primary motor cortex disinhibition during motor skill learning.

    PubMed

    Coxon, James P; Peat, Nicola M; Byblow, Winston D

    2014-07-01

    Motor learning requires practice over a period of time and depends on brain plasticity, yet even for relatively simple movements, there are multiple practice strategies that can be used for skill acquisition. We investigated the role of intracortical inhibition in the primary motor cortex (M1) during motor skill learning. Event-related transcranial magnetic stimulation (TMS) was used to assess corticomotor excitability and inhibition thought to involve synaptic and extrasynaptic γ-aminobutyric acid (GABA). Short intracortical inhibition (SICI) was assessed using 1- and 2.5-ms interstimulus intervals (ISIs). Participants learned a novel, sequential pinch-grip task on a computer in either a repetitive or interleaved practice structure. Both practice structures showed equivalent levels of motor performance at the end of acquisition and at retention 1 wk later. There was a novel task-related modulation of 1-ms SICI. Repetitive practice elicited a greater reduction of 1- and 2.5-ms SICI, i.e., disinhibition, between rest and task acquisition, compared with interleaved practice. These novel findings support the use of a repetitive practice structure for motor learning because the associated effects within M1 have relevance for motor rehabilitation. Copyright © 2014 the American Physiological Society.

  10. Three Dimensional Primary Hepatocyte Culture

    NASA Technical Reports Server (NTRS)

    Yoffe, Boris

    1998-01-01

    Our results demonstrated for the first time the feasibility of culturing PHH in microgravity bioreactors that exceeded the longest period obtained using other methods. Within the first week of culture, isolated hepatocytes started to form aggregates, which continuously increased in size (up to 1 cm) and macroscopically appeared as a multidimensional tissue-like assembly. To improve oxygenation and nutrition within the spheroids we performed experiments with the biodegradable nonwoven fiber-based polymers made from PolyGlycolic Acid (PGA). It has been shown that PGA scaffolds stimulate isolated cells to regenerate tissue with defined sizes and shapes and are currently being studied for various tissue-engineering applications. Our data demonstrated that culturing hepatocytes in the presence of PGA scaffolds resulted in more efficient cell assembly and formations of larger cell spheroids (up to 3 cm in length, see figure). The histology of cell aggregates cultured with PGA showed polymer fibers with attached hepatocytes. We initiated experiments to co-culture primary human hepatocytes with human microvascular endothelial cells in the bioreactor. The presence of endothelial cells in co-cultures were established by immunohistochemistry using anti-CD34 monoclonal Ab. Our preliminary data demonstrated that cultures of purified hepatocytes with human microvascular endothelial cells exhibited better growth and expressed higher levels of albumin MRNA for a longer period of time than cultures of ppfified, primary human hepatocytes cultured alone. We also evaluated microsomal deethylation activity of hepatocytes cultured in the presence of endothelial cells.In summary, we have established liver cell culture, which mimicked the structure and function of the parent tissue.

  11. Repetitive Transcranial Magnetic Stimulation to the Primary Motor Cortex Interferes with Motor Learning by Observing

    ERIC Educational Resources Information Center

    Brown, Liana E.; Wilson, Elizabeth T.; Gribble, Paul L.

    2009-01-01

    Neural representations of novel motor skills can be acquired through visual observation. We used repetitive transcranial magnetic stimulation (rTMS) to test the idea that this "motor learning by observing" is based on engagement of neural processes for learning in the primary motor cortex (M1). Human subjects who observed another person learning…

  12. Repetitive Transcranial Magnetic Stimulation to the Primary Motor Cortex Interferes with Motor Learning by Observing

    ERIC Educational Resources Information Center

    Brown, Liana E.; Wilson, Elizabeth T.; Gribble, Paul L.

    2009-01-01

    Neural representations of novel motor skills can be acquired through visual observation. We used repetitive transcranial magnetic stimulation (rTMS) to test the idea that this "motor learning by observing" is based on engagement of neural processes for learning in the primary motor cortex (M1). Human subjects who observed another person learning…

  13. Theta-burst stimulation over primary motor cortex degrades early motor learning.

    PubMed

    Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Agostino, Rocco; Nardella, Andrea; Berardelli, Alfredo

    2010-02-01

    Theta-burst stimulation (TBS) is currently used for inducing long-lasting changes in primary motor cortex (M1) excitability. More information is needed on how M1 is involved in early motor learning (practice-related improvement in motor performance, motor retention and motor consolidation). We investigated whether inhibitory continuous TBS (cTBS) is an effective experimental approach for modulating early motor learning of a simple finger movement in healthy humans. In a short task, 11 subjects practised 160 movements, and in a longer task also testing motor consolidation ten subjects practised 600 movements. During both experiments subjects randomly received real or sham cTBS over the left M1. Motor evoked potentials were tested at baseline and 7 min after cTBS. In the 160-movement experiment to test motor retention, 20 movements were repeated 30 min after motor practice ended. In the 600-movement experiment motor retention was assessed 15 and 30 min after motor practice ended, motor consolidation was tested by performing 20 movements 24 h after motor practice ended. Kinematic variables - movement amplitude, peak velocity and peak acceleration - were measured. cTBS significantly reduced the practice-related improvement in motor performance of finger movements in the experiment involving 160 movements and in the first part of the experiment involving 600 movements. After cTBS, peak velocity and peak acceleration of the 20 movements testing motor retention decreased whereas those testing motor consolidation remained unchanged. cTBS over M1 degrades practice-related improvement in motor performance and motor retention, but not motor consolidation of a voluntary finger movement.

  14. Parieto-motor cortical dysfunction in primary cervical dystonia.

    PubMed

    Porcacchia, Paolo; Palomar, Francisco J; Cáceres-Redondo, María T; Huertas-Fernández, Ismael; Martín-Rodríguez, Juan F; Carrillo, Fátima; Koch, Giacomo; Mir, Pablo

    2014-01-01

    Dystonia is considered as a motor network disorder involving the dysfunction of the posterior parietal cortex, a region involved in preparing and executing reaching movements. We used transcranial magnetic stimulation to test the hypothesis that cervical dystonic patients may have a disrupted parieto-motor connectivity. We enrolled 14 patients with primary cervical dystonia and 14 controls. A paired-pulse transcranial magnetic stimulation protocol was applied over the right posterior parietal cortex and the right primary motor area. Changes in the amplitudes of motor evoked potential were analyzed as an index of parieto-motor effective connectivity. Patients and healthy subjects were also evaluated with a reaching task. Reaction and movement times were measured. In healthy subjects, but not in dystonic patients, there was a facilitation of motor evoked potential amplitudes when the conditioning parietal stimulus preceded the test stimulus applied over the primary motor area by 4 ms. Reaction and movement times were significantly slower in patients than in controls. In dystonic patients, the relative strength of parieto-motor connectivity correlated with movement times. Parieto-motor cortical connectivity is impaired in cervical dystonic patients. This neurophysiological trait is associated with slower reaching movements. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Primary Motor Cortex Involvement in Initial Learning during Visuomotor Adaptation

    ERIC Educational Resources Information Center

    Riek, Stephan; Hinder, Mark R.; Carson, Richard G.

    2012-01-01

    Human motor behaviour is continually modified on the basis of errors between desired and actual movement outcomes. It is emerging that the role played by the primary motor cortex (M1) in this process is contingent upon a variety of factors, including the nature of the task being performed, and the stage of learning. Here we used repetitive TMS to…

  16. Primary Motor Cortex Involvement in Initial Learning during Visuomotor Adaptation

    ERIC Educational Resources Information Center

    Riek, Stephan; Hinder, Mark R.; Carson, Richard G.

    2012-01-01

    Human motor behaviour is continually modified on the basis of errors between desired and actual movement outcomes. It is emerging that the role played by the primary motor cortex (M1) in this process is contingent upon a variety of factors, including the nature of the task being performed, and the stage of learning. Here we used repetitive TMS to…

  17. Primary somatosensory cortex hand representation dynamically modulated by motor output.

    PubMed

    McGeoch, Paul D; Brang, David; Huang, Mingxiong; Ramachandran, V S

    2015-02-01

    The brain's primary motor and primary somatosensory cortices are generally viewed as functionally distinct entities. Here we show by means of magnetoencephalography with a phantom-limb patient, that movement of the phantom hand leads to a change in the response of the primary somatosensory cortex to tactile stimulation. This change correlates with the described conscious perception and suggests a greater degree of functional unification between the primary motor and somatosensory cortices than is currently realized. We suggest that this may reflect the evolution of this part of the human brain, which is thought to have occurred from an undifferentiated sensorimotor cortex.

  18. Different Modulation of Common Motor Information in Rat Primary and Secondary Motor Cortices

    PubMed Central

    Saiki, Akiko; Kimura, Rie; Samura, Toshikazu; Fujiwara-Tsukamoto, Yoko; Sakai, Yutaka; Isomura, Yoshikazu

    2014-01-01

    Rodents have primary and secondary motor cortices that are involved in the execution of voluntary movements via their direct and parallel projections to the spinal cord. However, it is unclear whether the rodent secondary motor cortex has any motor function distinct from the primary motor cortex to properly control voluntary movements. In the present study, we quantitatively examined neuronal activity in the caudal forelimb area (CFA) of the primary motor cortex and rostral forelimb area (RFA) of the secondary motor cortex in head-fixed rats performing forelimb movements (pushing, holding, and pulling a lever). We found virtually no major differences between CFA and RFA neurons, regardless of neuron subtypes, not only in their basal spiking properties but also in the time-course, amplitude, and direction preference of their functional activation for simple forelimb movements. However, the RFA neurons, as compared with the CFA neurons, showed obviously a greater susceptibility of their functional activation to an alteration in a behavioral situation, a 'rewarding' response that leads to reward or a 'consummatory' response that follows reward water, which might be accompanied by some internal adaptations without affecting the motor outputs. Our results suggest that, although the CFA and RFA neurons commonly process fundamental motor information to properly control forelimb movements, the RFA neurons may be functionally differentiated to integrate motor information with internal state information for an adaptation to goal-directed behaviors. PMID:24893154

  19. Neurotrophic Requirements of Human Motor Neurons Defined Using Amplified and Purified Stem Cell-Derived Cultures

    PubMed Central

    Lamas, Nuno Jorge; Johnson-Kerner, Bethany; Roybon, Laurent; Kim, Yoon A.; Garcia-Diaz, Alejandro; Wichterle, Hynek; Henderson, Christopher E.

    2014-01-01

    Human motor neurons derived from embryonic and induced pluripotent stem cells (hESCs and hiPSCs) are a potentially important tool for studying motor neuron survival and pathological cell death. However, their basic survival requirements remain poorly characterized. Here, we sought to optimize a robust survival assay and characterize their response to different neurotrophic factors. First, to increase motor neuron yield, we screened a small-molecule collection and found that the Rho-associated kinase (ROCK) inhibitor Y-27632 enhances motor neuron progenitor proliferation up to 4-fold in hESC and hiPSC cultures. Next, we FACS-purified motor neurons expressing the Hb9::GFP reporter from Y-27632-amplified embryoid bodies and cultured them in the presence of mitotic inhibitors to eliminate dividing progenitors. Survival of these purified motor neurons in the absence of any other cell type was strongly dependent on neurotrophic support. GDNF, BDNF and CNTF all showed potent survival effects (EC50 1–2 pM). The number of surviving motor neurons was further enhanced in the presence of forskolin and IBMX, agents that increase endogenous cAMP levels. As a demonstration of the ability of the assay to detect novel neurotrophic agents, Y-27632 itself was found to support human motor neuron survival. Thus, purified human stem cell-derived motor neurons show survival requirements similar to those of primary rodent motor neurons and can be used for rigorous cell-based screening. PMID:25337699

  20. Motor Speech Disorders Associated with Primary Progressive Aphasia

    PubMed Central

    Duffy, Joseph R.; Strand, Edythe A.; Josephs, Keith A.

    2014-01-01

    Background Primary progressive aphasia (PPA) and conditions that overlap with it can be accompanied by motor speech disorders. Recognition and understanding of motor speech disorders can contribute to a fuller clinical understanding of PPA and its management as well as its localization and underlying pathology. Aims To review the types of motor speech disorders that may occur with PPA, its primary variants, and its overlap syndromes (progressive supranuclear palsy syndrome, corticobasal syndrome, motor neuron disease), as well as with primary progressive apraxia of speech. Main Contribution The review should assist clinicians' and researchers' understanding of the relationship between motor speech disorders and PPA and its major variants. It also highlights the importance of recognizing neurodegenerative apraxia of speech as a condition that can occur with little or no evidence of aphasia. Conclusion Motor speech disorders can occur with PPA. Their recognition can contribute to clinical diagnosis and management of PPA and to understanding and predicting the localization and pathology associated with PPA variants and conditions that can overlap with them. PMID:25309017

  1. Brain Activation in Primary Motor and Somatosensory Cortices during Motor Imagery Correlates with Motor Imagery Ability in Stroke Patients

    PubMed Central

    Confalonieri, Linda; Pagnoni, Giuseppe; Barsalou, Lawrence W.; Rajendra, Justin; Eickhoff, Simon B.; Butler, Andrew J.

    2012-01-01

    Aims. While studies on healthy subjects have shown a partial overlap between the motor execution and motor imagery neural circuits, few have investigated brain activity during motor imagery in stroke patients with hemiparesis. This work is aimed at examining similarities between motor imagery and execution in a group of stroke patients. Materials and Methods. Eleven patients were asked to perform a visuomotor tracking task by either physically or mentally tracking a sine wave force target using their thumb and index finger during fMRI scanning. MIQ-RS questionnaire has been administered. Results and Conclusion. Whole-brain analyses confirmed shared neural substrates between motor imagery and motor execution in bilateral premotor cortex, SMA, and in the contralesional inferior parietal lobule. Additional region of interest-based analyses revealed a negative correlation between kinaesthetic imagery ability and percentage BOLD change in areas 4p and 3a; higher imagery ability was associated with negative and lower percentage BOLD change in primary sensorimotor areas during motor imagery. PMID:23378930

  2. Therapeutic potential of mesenchymal stromal cells and MSC conditioned medium in Amyotrophic Lateral Sclerosis (ALS)--in vitro evidence from primary motor neuron cultures, NSC-34 cells, astrocytes and microglia.

    PubMed

    Sun, Hui; Bénardais, Karelle; Stanslowsky, Nancy; Thau-Habermann, Nadine; Hensel, Niko; Huang, Dongya; Claus, Peter; Dengler, Reinhard; Stangel, Martin; Petri, Susanne

    2013-01-01

    Administration of mesenchymal stromal cells (MSC) improves functional outcome in the SOD1G93A mouse model of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) as well as in models of other neurological disorders. We have now investigated the effect of the interaction between MSC and motor neurons (derived from both non-transgenic and mutant SOD1G93A transgenic mice), NSC-34 cells and glial cells (astrocytes, microglia) (derived again from both non-transgenic and mutant SOD1G93A ALS transgenic mice) in vitro. In primary motor neurons, NSC-34 cells and astrocytes, MSC conditioned medium (MSC CM) attenuated staurosporine (STS) - induced apoptosis in a concentration-dependent manner. Studying MSC CM-induced expression of neurotrophic factors in astrocytes and NSC-34 cells, we found that glial cell line-derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) gene expression in astrocytes were significantly enhanced by MSC CM, with differential responses of non-transgenic and mutant astrocytes. Expression of Vascular Endothelial Growth Factor (VEGF) in NSC-34 cells was significantly upregulated upon MSC CM-treatment. MSC CM significantly reduced the expression of the cytokines TNFα and IL-6 and iNOS both in transgenic and non-transgenic astrocytes. Gene expression of the neuroprotective chemokine Fractalkine (CX3CL1) was also upregulated in mutant SOD1G93A transgenic astrocytes by MSC CM treatment. Correspondingly, MSC CM increased the respective receptor, CX3CR1, in mutant SOD1G93A transgenic microglia. Our data demonstrate that MSC modulate motor neuronal and glial response to apoptosis and inflammation. MSC therefore represent an interesting candidate for further preclinical and clinical evaluation in ALS.

  3. Parietal transcranial direct current stimulation modulates primary motor cortex excitability.

    PubMed

    Rivera-Urbina, Guadalupe Nathzidy; Batsikadze, Giorgi; Molero-Chamizo, Andrés; Paulus, Walter; Kuo, Min-Fang; Nitsche, Michael A

    2015-03-01

    The posterior parietal cortex is part of the cortical network involved in motor learning and is structurally and functionally connected with the primary motor cortex (M1). Neuroplastic alterations of neuronal connectivity might be an important basis for learning processes. These have however not been explored for parieto-motor connections in humans by transcranial direct current stimulation (tDCS). Exploring tDCS effects on parieto-motor cortical connectivity might be functionally relevant, because tDCS has been shown to improve motor learning. We aimed to explore plastic alterations of parieto-motor cortical connections by tDCS in healthy humans. We measured neuroplastic changes of corticospinal excitability via motor evoked potentials (MEP) elicited by single-pulse transcranial magnetic stimulation (TMS) before and after tDCS over the left posterior parietal cortex (P3), and 3 cm posterior or lateral to P3, to explore the spatial specificity of the effects. Furthermore, short-interval intracortical inhibition/intracortical facilitation (SICI/ICF) over M1, and parieto-motor cortical connectivity were obtained before and after P3 tDCS. The results show polarity-dependent M1 excitability alterations primarily after P3 tDCS. Single-pulse TMS-elicited MEPs, M1 SICI/ICF at 5 and 7 ms and 10 and 15 ms interstimulus intervals (ISIs), and parieto-motor connectivity at 10 and 15 ms ISIs were all enhanced by anodal stimulation. Single pulse-TMS-elicited MEPs, and parieto-motor connectivity at 10 and 15 ms ISIs were reduced by cathodal tDCS. The respective corticospinal excitability alterations lasted for at least 120 min after stimulation. These results show an effect of remote stimulation of parietal areas on M1 excitability. The spatial specificity of the effects and the impact on parietal cortex-motor cortex connections suggest a relevant connectivity-driven effect.

  4. The current status of primary hepatocyte culture

    PubMed Central

    Mitaka, Toshihiro

    1998-01-01

    Recently, there have been significant advances toward the development of culture conditions that promote proliferation of primary rodent hepatocytes. There are two major methods for the multiplication of hepatocytes in vitro: one is the use of nicotinamide, the other is the use of a nutrient-rich medium. In the medium containing a high concentration of nicotinamide and a growth factor, primary hepatocytes can proliferate well. In this culture condition small mononucleate cells, which are named small hepatocytes, appear and form colonies. Small hepatocytes have a high potential to proliferate while maintaining hepatic characteristics, and can differentiate into mature ones. On the other hand, combining the nutrient-rich medium with 2% DMSO, the proliferated hepatocytes can recover the hepatic differentiated functions and maintain them for a long time. In this review I describe the culture conditions for the proliferation and differentiation of primary hepatocytes and discuss the small hepatocytes, especially their roles in liver growth. PMID:10319020

  5. Unilateral nasal obstruction affects motor representation development within the face primary motor cortex in growing rats.

    PubMed

    Abe, Yasunori; Kato, Chiho; Uchima Koecklin, Karin Harumi; Okihara, Hidemasa; Ishida, Takayoshi; Fujita, Koichi; Yabushita, Tadachika; Kokai, Satoshi; Ono, Takashi

    2017-03-23

    Postnatal growth is influenced by genetic and environmental factors. Nasal obstruction during growth alters the electromyographic activity of orofacial muscles. The facial primary motor area represents muscles of the tongue and jaw, which are essential in regulating orofacial motor functions, including chewing and jaw opening. This study aimed to evaluate the effect of chronic unilateral nasal obstruction during growth on the motor representations within the face primary motor cortex (M1). Seventy-two 6-day-old male Wistar rats were randomly divided into control (n = 36) and experimental (n = 36) groups. Rats in the experimental group underwent unilateral nasal obstruction after cauterization of the external nostril at 8 days of age. Intracortical microstimulation (ICMS) mapping was performed when the rats were 5, 7, 9, and 11 weeks old in control and experimental groups (n = 9 per group per time point). Repeated-measures multivariate analysis of variance was used for intergroup and intragroup statistical comparisons. In the control and experimental groups, the total number of positive ICMS sites for the genioglossus and anterior digastric muscles was significantly higher at 5, 7, and 9 weeks, but there was no significant difference between 9 and 11 weeks of age. Moreover, the total number of positive ICMS sites was significantly smaller in the experimental group than in the control at each age. It is possible that nasal obstruction induced the initial changes in orofacial motor behavior in response to the altered respiratory pattern, which eventually contributed to face-M1 neuroplasticity.

  6. Brain correlates to facial motor imagery and its somatotopy in the primary motor cortex.

    PubMed

    Soliman, Ramy S; Lee, Sanghoon; Eun, Seulgi; Mohamed, Abdalla Z; Lee, Jeungchan; Lee, Eunyoung; Makary, Meena M; Kathy Lee, Seung Min; Lee, Hwa-Jin; Choi, Woo Suk; Park, Kyungmo

    2017-03-22

    Motor imagery (MI) has attracted increased interest for motor rehabilitation as many studies have shown that MI shares the same neural networks as motor execution (ME). Nevertheless, MI in terms of facial movement has not been studied extensively; thus, in the present study, we investigated shared neural networks between facial motor imagery (FMI) and facial motor execution (FME). In addition, FMI somatotopy within-face was investigated between the forehead and the mouth. Functional MRI was used to examine 34 healthy individuals with ME and MI paradigms for the forehead and the mouth. The general linear model and a paired t-test were performed to define the facial area in the primary motor cortex (M1) and this area has been used to investigate somatotopy between the forehead and mouth FMI. FMI recruited similar brain motor areas as FME, but showed less neural activity in all activated regions. The facial areas in M1 were distinguishable from other body movements such as finger movement. Further investigation of this area showed that forehead and mouth imagery tended to lack a somatotopic representation for position on M1, and yet had distinct characteristics in terms of neural activity level. FMI showed different characteristics from general MI as the former exclusively activated facial processing areas. In addition, FME and FMI showed different characteristics in terms of BOLD signal level, while sharing the same neural areas. The results imply a potential usefulness of MI training for rehabilitation of facial motor disease considering that forehead and mouth somatotopy showed no clear position difference, and yet showed a significant BOLD signal intensity variation.

  7. Interactions Among Learning Stage, Retention, and Primary Motor Cortex Excitability in Motor Skill Learning.

    PubMed

    Hirano, Masato; Kubota, Shinji; Tanabe, Shigeo; Koizume, Yoshiki; Funase, Kozo

    2015-01-01

    Previous studies have shown that primary motor cortex (M1) excitability is modulated by motor skill learning and that the M1 plays a crucial role in motor memory. However, the following questions remain: (1) At what stage do changes in M1 excitability occur? (2) Are learning-induced changes in leg M1 excitability associated with motor memory? Here, we did two experiments to answer these questions. In experiment 1, subjects learned a visuomotor tracking task over two consecutive days. Before and after the task in Day 1, we recorded input-output curves of the motor evoked potentials (I-O curve) produced in the tibialis anterior muscle by transcranial magnetic stimulation. We found that the changes in M1 excitability were affected by learning stage. In addition, the changes in M1 excitability in Day 1 were correlated with the retention. In experiment 2, we recorded I-O curves before learning, after the fast-learning stage, and after learning. We found no changes in M1 excitability immediately after the fast-learning stage. Furthermore, a significant relationship between the length of slow-learning stage and the changes in M1 excitability was detected. Previous studies have suggested that optimal motor commands are repeatedly used during the slow-learning stage. Therefore, present results indicate that changes in M1 excitability occur during the slow-learning stage and that such changes are proportional to motor skill retention because use-dependent plasticity occur by repetitive use of same motor commands during the slow-learning stage. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Growth of primary motor neurons on horizontally aligned carbon nanotube thin films and striped patterns

    NASA Astrophysics Data System (ADS)

    Roberts, Megan J.; Leach, Michelle K.; Bedewy, Mostafa; Meshot, Eric R.; Copic, Davor; Corey, Joseph M.; Hart, A. John

    2014-06-01

    Objective. Carbon nanotubes (CNTs) are attractive for use in peripheral nerve interfaces because of their unique combination of strength, flexibility, electrical conductivity and nanoscale surface texture. Here we investigated the growth of motor neurons on thin films of horizontally aligned CNTs (HACNTs). Approach. We cultured primary embryonic rat motor neurons on HACNTs and performed statistical analysis of the length and orientation of neurites. We next presented motor neurons with substrates of alternating stripes of HACNTs and SiO2. Main results. The neurons survived on HACNT substrates for up to eight days, which was the full duration of our experiments. Statistical analysis of the length and orientation of neurites indicated that the longest neurites on HACNTs tended to align with the CNT direction, although the average neurite length was similar between HACNTs and glass control substrates. We observed that when motor neurons were presented with alternating stripes of HACNTs and SiO2, the proportion of neurons on HACNTs increases over time, suggesting that neurons selectively migrate toward and adhere to the HACNT surface. Significance. The behavior of motor neurons on CNTs has not been previously investigated, and we show that aligned CNTs could provide a viable interface material to motor neurons. Combined with emerging techniques to build complex hierarchical structures of CNTs, our results suggest that organised CNTs could be incorporated into nerve grafts that use physical and electrical cues to guide regenerating axons.

  9. Primary motor cortex activity is elevated with incremental exercise intensity.

    PubMed

    Brümmer, V; Schneider, S; Strüder, H K; Askew, C D

    2011-05-05

    While the effects of exercise on brain cortical activity from pre-to post-exercise have been thoroughly evaluated, few studies have investigated the change in activity during exercise. As such, it is not clear to what extent changes in exercise intensity influence brain cortical activity. Furthermore, due to the difficulty in using brain-imaging methods during complex whole-body movements like cycling, it is unclear to what extent the activity in specific brain areas is altered with incremental exercise intensity over time. Latterly, active electroencephalography (EEG) electrodes combined with source localization methods allow for the assessment of brain activity, measured as EEG current density, within specific cortical regions. The present study aimed to investigate the application of this method during exercise on a cycle ergometer, and to investigate the effect of increasing exercise intensity on the magnitude and location of any changes in electrocortical current density. Subjects performed an incremental cycle ergometer test until subjective exhaustion. Current density of the EEG recordings during each test stage, as well as before and after exercise, was determined. Spatial changes in current density were localized using low-resolution brain electromagnetic tomography (LORETA) to three regions of interest; the primary motor cortex, primary sensory cortex and prefrontal cortex, and were expressed relative to current density within the local lobe. It was demonstrated that the relative current density of the primary motor cortex was intensified with increasing exercise intensity, whereas activity of the primary sensory cortex and that of the prefrontal cortex were not altered with exercise. The results indicate that the combined active EEG/LORETA method allows for the recording of brain cortical activity during complex movements and incremental exercise. These findings indicate that primary motor cortex activity is elevated with incremental exercise intensity

  10. Concurrent TMS to the primary motor cortex augments slow motor learning.

    PubMed

    Narayana, Shalini; Zhang, Wei; Rogers, William; Strickland, Casey; Franklin, Crystal; Lancaster, Jack L; Fox, Peter T

    2014-01-15

    Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up- (or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was measured by H2(15)O PET at baseline and after 4 weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4 weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy.

  11. Concurrent TMS to the primary motor cortex augments slow motor learning

    PubMed Central

    Narayana, Shalini; Zhang, Wei; Rogers, William; Strickland, Casey; Franklin, Crystal; Lancaster, Jack L.; Fox, Peter T.

    2013-01-01

    Transcranial magnetic stimulation (TMS) has shown promise as a treatment tool, with one FDA approved use. While TMS alone is able to up- (or down-) regulate a targeted neural system, we argue that TMS applied as an adjuvant is more effective for repetitive physical, behavioral and cognitive therapies, that is, therapies which are designed to alter the network properties of neural systems through Hebbian learning. We tested this hypothesis in the context of a slow motor learning paradigm. Healthy right-handed individuals were assigned to receive 5 Hz TMS (TMS group) or sham TMS (sham group) to the right primary motor cortex (M1) as they performed daily motor practice of a digit sequence task with their non-dominant hand for 4 weeks. Resting cerebral blood flow (CBF) was measured by H215O PET at baseline and after 4 weeks of practice. Sequence performance was measured daily as the number of correct sequences performed, and modeled using a hyperbolic function. Sequence performance increased significantly at 4 weeks relative to baseline in both groups. The TMS group had a significant additional improvement in performance, specifically, in the rate of skill acquisition. In both groups, an improvement in sequence timing and transfer of skills to non-trained motor domains was also found. Compared to the sham group, the TMS group demonstrated increases in resting CBF specifically in regions known to mediate skill learning namely, the M1, cingulate cortex, putamen, hippocampus, and cerebellum. These results indicate that TMS applied concomitantly augments behavioral effects of motor practice, with corresponding neural plasticity in motor sequence learning network. These findings are the first demonstration of the behavioral and neural enhancing effects of TMS on slow motor practice and have direct application in neurorehabilitation where TMS could be applied in conjunction with physical therapy. PMID:23867557

  12. Effect of tactile stimulation on primary motor cortex excitability during action observation combined with motor imagery.

    PubMed

    Tanaka, Megumi; Kubota, Shinji; Onmyoji, Yusuke; Hirano, Masato; Uehara, Kazumasa; Morishita, Takuya; Funase, Kozo

    2015-07-23

    We aimed to investigate the effects of the tactile stimulation to an observer's fingertips at the moment that they saw an object being pinched by another person on the excitability of observer's primary motor cortex (M1) using transcranial magnetic stimulation (TMS). In addition, the above effects were also examined during action observation combined with the motor imagery. Motor evoked potentials (MEP) were evoked from the subjects' right first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles. Electrical stimulation (ES) inducing tactile sensation was delivered to the subjects' first and second fingertips at the moment of pinching action performed by another person. Although neither the ES nor action observation alone had significant effects on the MEP amplitude of the FDI or ADM, the FDI MEP amplitude which acts as the prime mover during pinching was reduced when ES and action observation were combined; however, no such changes were seen in the ADM. Conversely, that reduced FDI MEP amplitude was increased during the motor imagery. These results indicated that the M1 excitability during the action observation of pinching action combined with motor imagery could be enhanced by the tactile stimulation delivered to the observer's fingertips at the moment corresponding to the pinching being observed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. PRIMARY CULTURES OF DISSOCIATED SYMPATHETIC NEURONS

    PubMed Central

    Mains, Richard E.; Patterson, Paul H.

    1973-01-01

    Rat sympathetic ganglia were disrupted by mechanical agitation to yield dissociated primary neurons, and the conditions for long-term growth in culture of the isolated neurons were examined. The neurons were grown with or without non-neural cells, simply by the addition or deletion of bicarbonate during growth in culture. Fluorescence histochemistry indicated that the isolated neurons contained catecholamines; incubations with radioactive precursors were used to verify the synthesis and accumulation of both dopamine and norepinephrine. The neurons also produced octopamine using tyramine as precursor, but not with tyrosine as the precursor. In the presence of eserine, older cultures synthesized and stored small amounts of acetylcholine. The cultures did not synthesize and accumulate detectable levels of radioactive γ-aminobutyric acid, 5-hydroxytryptamine, or histamine. PMID:4616046

  14. Dependability of sensitivity tests in primary culture.

    PubMed Central

    Waterworth, P M; Del Piano, M

    1976-01-01

    Primary sensitivity tests were done on 90 specimens of infected urine, and the results were compared with those of secondary tests on pure cultures done by three diffusion methods. There was good correlation between the four methods. In a second study, the reliability of primary tests prepared in the clinical laboratory on specimens of pus was assessed, and the frequency with which a definitive result was obtained with different types of specimen was determined. Recommendations are made for the economic use of these tests. Images PMID:1270599

  15. Molluscan cells in culture: primary cell cultures and cell lines

    PubMed Central

    Yoshino, T. P.; Bickham, U.; Bayne, C. J.

    2013-01-01

    In vitro cell culture systems from molluscs have significantly contributed to our basic understanding of complex physiological processes occurring within or between tissue-specific cells, yielding information unattainable using intact animal models. In vitro cultures of neuronal cells from gastropods show how simplified cell models can inform our understanding of complex networks in intact organisms. Primary cell cultures from marine and freshwater bivalve and gastropod species are used as biomonitors for environmental contaminants, as models for gene transfer technologies, and for studies of innate immunity and neoplastic disease. Despite efforts to isolate proliferative cell lines from molluscs, the snail Biomphalaria glabrata Say, 1818 embryonic (Bge) cell line is the only existing cell line originating from any molluscan species. Taking an organ systems approach, this review summarizes efforts to establish molluscan cell cultures and describes the varied applications of primary cell cultures in research. Because of the unique status of the Bge cell line, an account is presented of the establishment of this cell line, and of how these cells have contributed to our understanding of snail host-parasite interactions. Finally, we detail the difficulties commonly encountered in efforts to establish cell lines from molluscs and discuss how these difficulties might be overcome. PMID:24198436

  16. Investigation of fMRI neurofeedback of differential primary motor cortex activity using kinesthetic motor imagery.

    PubMed

    Chiew, Mark; LaConte, Stephen M; Graham, Simon J

    2012-05-15

    Functional MRI neurofeedback (fMRI NF) is an emerging technique that trains subjects to regulate their brain activity while they manipulate sensory stimulus representations of fMRI signals in "real-time". Here we report an fMRI NF study of brain activity associated with kinesthetic motor imagery (kMI), analyzed using partial least squares (PLS), a multivariate analysis technique. Thirteen healthy young adult subjects performed kMI involving each hand separately, with NF training targeting regions of interest (ROIs) in the left and right primary motor cortex (M1). Throughout, subjects attempted to maximize a laterality index (LI) of brain activity-the difference in activity between the contralateral ROI (relative to the hand involved in kMI) and the ipsilateral M1 ROI-while receiving real-time updates on a visual display. Six of 13 subjects were successful in increasing the LI value, whereas the other 7 were not successful and performed similarly to 5 control subjects who received sham NF training. Ability to suppress activity in the ipsilateral M1 ROI was the primary driver of successful NF performance. Multiple PLS analyses depicted activated networks of brain regions involved with imagery, self-awareness, and feedback processing, and additionally showed that activation of the task positive network was correlated with task performance. These results indicate that fMRI NF of kMI is capable of modulating brain activity in primary motor regions in a subset of the population. In the future, such methods may be useful in the development of NF training methods for enhancing motor rehabilitation following stroke. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Induction of Motor Associative Plasticity in the Posterior Parietal Cortex–Primary Motor Network

    PubMed Central

    Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer; Carolina de Campos, Ana; Kukke, Sahana N.; Wu, Tianxia; Wang, Han; Hallett, Mark

    2015-01-01

    There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC–M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input–output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC–M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction. PMID:23968834

  18. Lubricating oil dominates primary organic aerosol emissions from motor vehicles.

    PubMed

    Worton, David R; Isaacman, Gabriel; Gentner, Drew R; Dallmann, Timothy R; Chan, Arthur W H; Ruehl, Christopher; Kirchstetter, Thomas W; Wilson, Kevin R; Harley, Robert A; Goldstein, Allen H

    2014-04-01

    Motor vehicles are major sources of primary organic aerosol (POA), which is a mixture of a large number of organic compounds that have not been comprehensively characterized. In this work, we apply a recently developed gas chromatography mass spectrometry approach utilizing "soft" vacuum ultraviolet photoionization to achieve unprecedented chemical characterization of motor vehicle POA emissions in a roadway tunnel with a mass closure of >60%. The observed POA was characterized by number of carbon atoms (NC), number of double bond equivalents (NDBE) and degree of molecular branching. Vehicular POA was observed to predominantly contain cycloalkanes with one or more rings and one or more branched alkyl side chains (≥80%) with low abundances of n-alkanes and aromatics (<5%), similar to "fresh" lubricating oil. The gas chromatography retention time data indicates that the cycloalkane ring structures are most likely dominated by cyclohexane and cyclopentane rings and not larger cycloalkanes. High molecular weight combustion byproducts, that is, alkenes, oxygenates, and aromatics, were not present in significant amounts. The observed carbon number and chemical composition of motor vehicle POA was consistent with lubricating oil being the dominant source from both gasoline and diesel-powered vehicles, with an additional smaller contribution from unburned diesel fuel and a negligible contribution from unburned gasoline.

  19. Primary motor cortex contributes to the implementation of implicit value-based rules during motor decisions.

    PubMed

    Derosiere, Gerard; Zénon, Alexandre; Alamia, Andrea; Duque, Julie

    2017-02-01

    In the present study, we investigated the functional contribution of the human primary motor cortex (M1) to motor decisions. Continuous theta burst stimulation (cTBS) was used to alter M1 activity while participants performed a decision-making task in which the reward associated with the subjects' responses (right hand finger movements) depended on explicit and implicit value-based rules. Subjects performed the task over two consecutive days and cTBS occurred in the middle of Day 2, once the subjects were just about to implement implicit rules, in addition to the explicit instructions, to choose their responses, as evident in the control group (cTBS over the right somatosensory cortex). Interestingly, cTBS over the left M1 prevented subjects from implementing the implicit value-based rule while its implementation was enhanced in the group receiving cTBS over the right M1. Hence, cTBS had opposite effects depending on whether it was applied on the contralateral or ipsilateral M1. The use of the explicit value-based rule was unaffected by cTBS in the three groups of subject. Overall, the present study provides evidence for a functional contribution of M1 to the implementation of freshly acquired implicit rules, possibly through its involvement in a cortico-subcortical network controlling value-based motor decisions.

  20. Representation of individual forelimb muscles in primary motor cortex.

    PubMed

    Hudson, Heather M; Park, Michael C; Belhaj-Saïf, Abderraouf; Cheney, Paul D

    2017-07-01

    Stimulus-triggered averaging (StTA) of forelimb muscle electromyographic (EMG) activity was used to investigate individual forelimb muscle representation within the primary motor cortex (M1) of rhesus macaques with the objective of determining the extent of intra-areal somatotopic organization. Two monkeys were trained to perform a reach-to-grasp task requiring multijoint coordination of the forelimb. EMG activity was simultaneously recorded from 24 forelimb muscles including 5 shoulder, 7 elbow, 5 wrist, 5 digit, and 2 intrinsic hand muscles. Microstimulation (15 µA at 15 Hz) was delivered throughout the movement task and individual stimuli were used as triggers for generating StTAs of EMG activity. StTAs were used to map the cortical representations of individual forelimb muscles. As reported previously (Park et al. 2001), cortical maps revealed a central core of distal muscle (wrist, digit, and intrinsic hand) representation surrounded by a horseshoe-shaped proximal (shoulder and elbow) muscle representation. In the present study, we found that shoulder and elbow flexor muscles were predominantly represented in the lateral branch of the horseshoe whereas extensors were predominantly represented in the medial branch. Distal muscles were represented within the core distal forelimb representation and showed extensive overlap. For the first time, we also show maps of inhibitory output from motor cortex, which follow many of the same organizational features as the maps of excitatory output.NEW & NOTEWORTHY While the orderly representation of major body parts along the precentral gyrus has been known for decades, questions have been raised about the possible existence of additional more detailed aspects of somatotopy. In this study, we have investigated this question with respect to muscles of the arm and show consistent features of within-arm (intra-areal) somatotopic organization. For the first time we also show maps of how inhibitory output from motor cortex is

  1. Induction of motor associative plasticity in the posterior parietal cortex-primary motor network.

    PubMed

    Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer; Carolina de Campos, Ana; Kukke, Sahana N; Wu, Tianxia; Wang, Han; Hallett, Mark

    2015-02-01

    There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC-M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input-output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction. Published by Oxford University Press 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Optimization of mirror therapy to excite ipsilateral primary motor cortex.

    PubMed

    Hadoush, Hikmat; Mano, Hirofumi; Sunagawa, Toru; Nakanishi, Kazuyoshi; Ochi, Mitsu

    2013-01-01

    Mirror illusion therapy (mirror therapy) is based on the experimental substrate of a visual illusion of active hand movement to excite ipsilateral primary motor cortex (iM1). We tested whether iM1 excitability could be modulated by enabling or disabling vision of the active hand during mirror therapy. Motor cortical activations of healthy right-handed participants were identified by magnetoencephalography. Participants performed voluntary index finger extension of their dominant and non-dominant hands, separately, while viewing mirror reflection images of their active hand superimposed upon their hidden inactive hand. This was performed either with vision of the active hand (uncovered viewing condition) or without vision of the active hand (covered viewing condition). In the covered viewing condition, the iM1could be excited in all participants (n = 10) and this excitation did not differ whether the active hand was the dominant or non-dominant hand. However, in the uncovered viewing condition, dominant and non-dominant hands were able to excite iM1 only in some participants (n = 4 and n = 7, respectively). Moreover, the participants' responses to the illusion validation questionnaire revealed that the covered viewing condition could cause clearer visual illusion for the active hand than the uncovered viewing condition. Disabling vision of the active hand during mirror therapy was more effective to excite iM1 responses by creating more immersive visual illusion of the active hand.

  3. High Working Memory Load Increases Intracortical Inhibition in Primary Motor Cortex and Diminishes the Motor Affordance Effect.

    PubMed

    Freeman, Scott M; Itthipuripat, Sirawaj; Aron, Adam R

    2016-05-18

    Motor affordances occur when the visual properties of an object elicit behaviorally relevant motor representations. Typically, motor affordances only produce subtle effects on response time or on motor activity indexed by neuroimaging/neuroelectrophysiology, but sometimes they can trigger action itself. This is apparent in "utilization behavior," where individuals with frontal cortex damage inappropriately grasp affording objects. This raises the possibility that, in healthy-functioning individuals, frontal cortex helps ensure that irrelevant affordance provocations remain below the threshold for actual movement. In Experiment 1, we tested this "frontal control" hypothesis by "loading" the frontal cortex with an effortful working memory (WM) task (which ostensibly consumes frontal resources) and examined whether this increased EEG measures of motor affordances to irrelevant affording objects. Under low WM load, there were typical motor affordance signatures: an event-related desynchronization in the mu frequency and an increased P300 amplitude for affording (vs nonaffording) objects over centroparietal electrodes. Contrary to our prediction, however, these affordance measures were diminished under high WM load. In Experiment 2, we tested competing mechanisms responsible for the diminished affordance in Experiment 1. We used paired-pulse transcranial magnetic stimulation over primary motor cortex to measure long-interval cortical inhibition. We found greater long-interval cortical inhibition for high versus low load both before and after the affording object, suggesting that a tonic inhibition state in primary motor cortex could prevent the affordance from provoking the motor system. Overall, our results suggest that a high WM load "sets" the motor system into a suppressed state that mitigates motor affordances. Is an irrelevant motor affordance more likely to be triggered when you are under low or high cognitive load? We examined this using physiological measures

  4. Prolonged Minocycline Treatment Impairs Motor Neuronal Survival and Glial Function in Organotypic Rat Spinal Cord Cultures

    PubMed Central

    Pinkernelle, Josephine; Fansa, Hisham; Ebmeyer, Uwe; Keilhoff, Gerburg

    2013-01-01

    Background Minocycline, a second-generation tetracycline antibiotic, exhibits anti-inflammatory and neuroprotective effects in various experimental models of neurological diseases, such as stroke, Alzheimer’s disease, amyotrophic lateral sclerosis and spinal cord injury. However, conflicting results have prompted a debate regarding the beneficial effects of minocycline. Methods In this study, we analyzed minocycline treatment in organotypic spinal cord cultures of neonatal rats as a model of motor neuron survival and regeneration after injury. Minocycline was administered in 2 different concentrations (10 and 100 µM) at various time points in culture and fixed after 1 week. Results Prolonged minocycline administration decreased the survival of motor neurons in the organotypic cultures. This effect was strongly enhanced with higher concentrations of minocycline. High concentrations of minocycline reduced the number of DAPI-positive cell nuclei in organotypic cultures and simultaneously inhibited microglial activation. Astrocytes, which covered the surface of the control organotypic cultures, revealed a peripheral distribution after early minocycline treatment. Thus, we further analyzed the effects of 100 µM minocycline on the viability and migration ability of dispersed primary glial cell cultures. We found that minocycline reduced cell viability, delayed wound closure in a scratch migration assay and increased connexin 43 protein levels in these cultures. Conclusions The administration of high doses of minocycline was deleterious for motor neuron survival. In addition, it inhibited microglial activation and impaired glial viability and migration. These data suggest that especially high doses of minocycline might have undesired affects in treatment of spinal cord injury. Further experiments are required to determine the conditions for the safe clinical administration of minocycline in spinal cord injured patients. PMID:23967343

  5. Sensory motor mechanisms unify psychology: the embodiment of culture

    PubMed Central

    Soliman, Tamer; Gibson, Alison; Glenberg, Arthur M.

    2013-01-01

    Sensorimotor mechanisms can unify explanations at cognitive, social, and cultural levels. As an example, we review how anticipated motor effort is used by individuals and groups to judge distance: the greater the anticipated effort the greater the perceived distance. Anticipated motor effort can also be used to understand cultural differences. People with interdependent self- construals interact almost exclusively with in-group members, and hence there is little opportunity to tune their sensorimotor systems for interaction with out-group members. The result is that interactions with out-group members are expected to be difficult and out-group members are perceived as literally more distant. In two experiments we show (a) interdependent Americans, compared to independent Americans, see American confederates (in-group) as closer; (b) interdependent Arabs, compared to independent Arabs, perceive Arab confederates (in- group) as closer, whereas interdependent Americans perceive Arab confederates (out-group) as farther. These results demonstrate how the same embodied mechanism can seamlessly contribute to explanations at the cognitive, social, and cultural levels. PMID:24348439

  6. Neurons in Primary Motor Cortex Engaged During Action Observation

    PubMed Central

    Dushanova, Juliana; Donoghue, John

    2010-01-01

    Neurons in higher cortical areas appear to become active during action observation, either by mirroring observed actions (termed mirror neurons) or by eliciting mental rehearsal of observed motor acts. We report the existence of neurons in primary motor cortex (MI) responding to viewed actions, an area generally considered to initiate and guide movement performance. Multielectrode recordings in monkeys performing or observing a well-learned step tracking task showed that approximately half of MI neurons, active when monkeys performed the task, were also active when they observed the action being performed by a human. These ‘view’ neurons were spatially intermingled with ‘do’ neurons, active only during movement performance. Simultaneously recorded, ‘view’ neurons comprised two groups: ∼38% retained the same preferred direction (PD) and timing during performance and viewing, while the remainder (62%) changed their PDs and time lag during viewing compared with performance. Nevertheless, population activity during viewing was sufficient to predict the direction and trajectory of viewed movements as action unfolded, although less accurately than during performance. ‘View’ neurons became less active and contained poorer representations of action when viewing only sub-components of the task. MI ‘view’ neurons thus appear to reflect the aspects of a learned movement when observed in others and form part of a broadly engaged set of cortical areas routinely responding to learned behaviors. These findings suggest that viewing a learned action elicits replay of aspects of MI activity needed to perform the observed action and could additionally reflect processing related to understanding, learning or mentally rehearsing action. PMID:20074212

  7. Acute aerobic exercise modulates primary motor cortex inhibition.

    PubMed

    Mooney, Ronan A; Coxon, James P; Cirillo, John; Glenny, Helen; Gant, Nicholas; Byblow, Winston D

    2016-12-01

    Aerobic exercise can enhance neuroplasticity although presently the neural mechanisms underpinning these benefits remain unclear. One possible mechanism is through effects on primary motor cortex (M1) function via down-regulation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The aim of the present study was to examine how corticomotor excitability (CME) and M1 intracortical inhibition are modulated in response to a single bout of moderate intensity aerobic exercise. Ten healthy right-handed adults were participants. Single- and paired-pulse transcranial magnetic stimulation was applied over left M1 to obtain motor-evoked potentials in the right flexor pollicis brevis. We examined CME, cortical silent period (SP) duration, short- and long-interval intracortical inhibition (SICI, LICI), and late cortical disinhibition (LCD), before and after acute aerobic exercise (exercise session) or an equivalent duration without exercise (control session). Aerobic exercise was performed on a cycle ergometer for 30 min at a workload equivalent to 60 % of maximal cardiorespiratory fitness (VO2 peak; heart rate reserve = 75 ± 3 %, perceived exertion = 13.5 ± 0.7). LICI was reduced at 10 (52 ± 17 %, P = 0.03) and 20 min (27 ± 8 %, P = 0.03) post-exercise compared to baseline (13 ± 4 %). No significant changes in CME, SP duration, SICI or LCD were observed. The present study shows that GABAB-mediated intracortical inhibition may be down-regulated after acute aerobic exercise. The potential effects this may have on M1 plasticity remain to be determined.

  8. 9 CFR 3.138 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Primary conveyances (motor vehicle, rail, air, and marine). 3.138 Section 3.138 Animals and Animal Products ANIMAL AND PLANT HEALTH... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used...

  9. 9 CFR 3.88 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Primary conveyances (motor vehicle, rail, air, and marine). 3.88 Section 3.88 Animals and Animal Products ANIMAL AND PLANT HEALTH... conveyances (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used...

  10. 9 CFR 3.88 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Primary conveyances (motor vehicle, rail, air, and marine). 3.88 Section 3.88 Animals and Animal Products ANIMAL AND PLANT HEALTH... conveyances (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used...

  11. 9 CFR 3.138 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Primary conveyances (motor vehicle, rail, air, and marine). 3.138 Section 3.138 Animals and Animal Products ANIMAL AND PLANT HEALTH... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used...

  12. Properties of the primary somatosensory cortex projection to the primary motor cortex in the mouse.

    PubMed

    Petrof, Iraklis; Viaene, Angela N; Sherman, S Murray

    2015-04-01

    The primary somatosensory (S1) and primary motor (M1) cortices are reciprocally connected, and their interaction has long been hypothesized to contribute to coordinated motor output. Very little is known, however, about the nature and synaptic properties of the S1 input to M1. Here we wanted to take advantage of a previously developed sensorimotor slice preparation that preserves much of the S1-to-M1 connectivity (Rocco MM, Brumberg JC. J Neurosci Methods 162: 139-147, 2007), as well as available optogenetic methodologies, in order to investigate the synaptic profile of this projection. Our data show that S1 input to pyramidal cells of M1 is highly homogeneous, possesses many features of a "driver" pathway, such as paired-pulse depression and lack of metabotropic glutamate receptor activation, and is mediated through axons that terminate in both small and large synaptic boutons. Our data suggest that S1 provides M1 with afferents that possess synaptic and anatomical characteristics ideal for the delivery of strong inputs that can "drive" postsynaptic M1 cells, thereby potentially affecting their output.

  13. Task-dependent engagements of the primary visual cortex during kinesthetic and visual motor imagery.

    PubMed

    Mizuguchi, Nobuaki; Nakamura, Maiko; Kanosue, Kazuyuki

    2017-01-01

    Motor imagery can be divided into kinesthetic and visual aspects. In the present study, we investigated excitability in the corticospinal tract and primary visual cortex (V1) during kinesthetic and visual motor imagery. To accomplish this, we measured motor evoked potentials (MEPs) and probability of phosphene occurrence during the two types of motor imageries of finger tapping. The MEPs and phosphenes were induced by transcranial magnetic stimulation to the primary motor cortex and V1, respectively. The amplitudes of MEPs and probability of phosphene occurrence during motor imagery were normalized based on the values obtained at rest. Corticospinal excitability increased during both kinesthetic and visual motor imagery, while excitability in V1 was increased only during visual motor imagery. These results imply that modulation of cortical excitability during kinesthetic and visual motor imagery is task dependent. The present finding aids in the understanding of the neural mechanisms underlying motor imagery and provides useful information for the use of motor imagery in rehabilitation or motor imagery training.

  14. Improvement in precision grip force control with self-modulation of primary motor cortex during motor imagery.

    PubMed

    Blefari, Maria L; Sulzer, James; Hepp-Reymond, Marie-Claude; Kollias, Spyros; Gassert, Roger

    2015-01-01

    Motor imagery (MI) has shown effectiveness in enhancing motor performance. This may be due to the common neural mechanisms underlying MI and motor execution (ME). The main region of the ME network, the primary motor cortex (M1), has been consistently linked to motor performance. However, the activation of M1 during motor imagery is controversial, which may account for inconsistent rehabilitation therapy outcomes using MI. Here, we examined the relationship between contralateral M1 (cM1) activation during MI and changes in sensorimotor performance. To aid cM1 activity modulation during MI, we used real-time fMRI neurofeedback-guided MI based on cM1 hand area blood oxygen level dependent (BOLD) signal in healthy subjects, performing kinesthetic MI of pinching. We used multiple regression analysis to examine the correlation between cM1 BOLD signal and changes in motor performance during an isometric pinching task of those subjects who were able to activate cM1 during motor imagery. Activities in premotor and parietal regions were used as covariates. We found that cM1 activity was positively correlated to improvements in accuracy as well as overall performance improvements, whereas other regions in the sensorimotor network were not. The association between cM1 activation during MI with performance changes indicates that subjects with stronger cM1 activation during MI may benefit more from MI training, with implications toward targeted neurotherapy.

  15. Temporal dynamics of primary motor cortex γ oscillation amplitude and piper corticomuscular coherence changes during motor control.

    PubMed

    Muthukumaraswamy, Suresh D

    2011-08-01

    In recent years, the use of non-invasive techniques (EEG/MEG) to measure the ~80 Hz ("gamma") oscillations generated by the primary motor cortex during motor control has been well validated. However, primary motor cortex gamma oscillations have yet to be systematically compared with lower frequency (30-50 Hz, 'piper') corticomuscular coherence in the same tasks. In this paper, primary cortex gamma oscillations and piper corticomuscular coherence are compared for three types of movements: simple abductions of the index finger, repetitive abductions of the index finger of different extents and frequencies and static abduction of the index finger at two different force levels. For simple movements, piper coherence and gamma amplitude followed very similar time courses with coherence appearing at approximately half the frequency of cortical gamma oscillations. No evidence of 2:1 phase-phase coupling was observed. A similar pattern of results was observed for repetitive movements varying in size and frequency; however, during the production of static force, the time courses became dissociated. During these movements, EMG piper amplitude was sustained for the entire contraction; gamma power showed a burst at onset but no piper corticomuscular coherence was observed. For these data, this dissociation suggests that while primary motor cortex gamma oscillations and piper corticomuscular coherence may often co-occur during the production of dynamic movements, they probably reflect different functional processes in motor control.

  16. Motor profile of Portuguese preschool children on the Peabody Developmental Motor Scales-2: a cross-cultural study.

    PubMed

    Saraiva, Linda; Rodrigues, Luís P; Cordovil, Rita; Barreiros, João

    2013-06-01

    This study was designed to examine the cultural sensitivity of the PDMS-2 for Portuguese preschool children aged 36-71 months. A total of 540 children (255 males and 285 females) from 15 public preschools of Viana do Castelo, Portugal, were assessed. Age and gender effects in motor performance were examined. Results indicated that PDMS-2 is valid instrument to differentiate Portuguese age groups. Girls presented higher scores than boys in the Grasping and Visuo-motor integration subtests and lower scores in the Object Manipulation subtest. Portuguese preschoolers performed above US norms on Grasping, Visual-motor integration, and Stationary subtests, and bellow on Locomotion and Object Manipulation subtests. Overall, Portuguese children showed better results on the Fine Motor Quotient comparing to the Gross Motor Quotient. These results underline different motor development profiles between Portuguese and American children. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Neuronal correlates of motor performance and motor learning in the primary motor cortex of monkeys adapting to an external force field.

    PubMed

    Li, C S; Padoa-Schioppa, C; Bizzi, E

    2001-05-01

    The primary motor cortex (M1) is known to control motor performance. Recent findings have also implicated M1 in motor learning, as neurons in this area show learning-related plasticity. In the present study, we analyzed the neuronal activity recorded in M1 in a force field adaptation task. Our goal was to investigate the neuronal reorganization across behavioral epochs (before, during, and after adaptation). Here we report two main findings. First, memory cells were present in two classes. With respect to the changes of preferred direction (Pd), these two classes complemented each other after readaptation. Second, for the entire neuronal population, the shift of Pd matched the shift observed for muscles. These results provide a framework whereby the activity of distinct neuronal subpopulations combines to subserve both functions of motor performance and motor learning.

  18. Region and task-specific activation of Arc in primary motor cortex of rats following motor skill learning.

    PubMed

    Hosp, J A; Mann, S; Wegenast-Braun, B M; Calhoun, M E; Luft, A R

    2013-10-10

    Motor learning requires protein synthesis within the primary motor cortex (M1). Here, we show that the immediate early gene Arc/Arg3.1 is specifically induced in M1 by learning a motor skill. Arc mRNA was quantified using a fluorescent in situ hybridization assay in adult Long-Evans rats learning a skilled reaching task (SRT), in rats performing reaching-like forelimb movement without learning (ACT) and in rats that were trained in the operant but not the motor elements of the task (controls). Apart from M1, Arc expression was assessed within the rostral motor area (RMA), primary somatosensory cortex (S1), striatum (ST) and cerebellum. In SRT animals, Arc mRNA levels in M1 contralateral to the trained limb were 31% higher than ipsilateral (p<0.001), 31% higher than in the contralateral M1 of ACT animals (p<0.001) and 48% higher than in controls (p<0.001). Arc mRNA expression in SRT was positively correlated with learning success between two sessions (r=0.52; p=0.026). For RMA, S1, ST or cerebellum no significant differences in Arc mRNA expression were found between hemispheres or across behaviors. As Arc expression has been related to different forms of cellular plasticity, these findings suggest a link between M1 Arc expression and motor skill learning in rats. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. Ischemic involvement of the primary motor cortex is a prognostic factor in acute stroke.

    PubMed

    Kaya, Dilaver; Dincer, Alp; Arman, Fehim; Bakirci, Nadi; Erzen, Canan; Pamir, M Necmettin

    2015-12-01

    The location of the primary motor cortex can be detected in healthy adults using the findings of 'T2 hypointensity' and the 'double layer sign' on 3 T diffusion-weighted imaging. The aim of this study was to assess whether ischemic involvement of the primary motor cortex can be identified on 3 T diffusion-weighted imaging within six-hours after stroke onset and to evaluate whether this finding could predict clinical outcome three-months after ischemic stroke. Sixty-five patients who had paralysis and ischemia of the anterior circulation underwent 3 T magnetic resonance imaging within six-hours of symptom onset. Follow-up MRI was obtained at 72 h. Anatomic localization and ischemic involvement of the primary motor cortex were evaluated on diffusion-weighted imaging by two investigators. Ischemic involvement on the primary motor cortex was classified into three grades. Ischemic lesion volumes were measured. We compared the favorable outcomes at three-months between subjects with and without ischemic involvement on the primary motor cortex using the NIHSS and modified Rankin Scale. Ischemic involvement on the primary motor cortex was identified in 52% of patients. Interrater agreement coefficients were 0·93 for the identification of ischemic involvement of primary motor cortex. As defined by scores on the modified Rankin Scale, among the patients with ischemic involvement of the primary motor cortex were worse than the patients without ischemic involvement of the primary motor cortex (P = 0·01). The mean ischemic lesion volume at baseline diffusion-weighted imaging was 38·7 ± 41·7 cm(3) and was 89·8 ± 93·6 cm(3) at follow-up T2-WI. Ischemic involvement on the primary motor cortex (odds ratio: 14·7) was a determinant for worse outcome. 3T diffusion-weighted imaging can identify ischemic involvement on the primary motor cortex and may provide useful information for predicting outcome during the hyperacute stage. Ischemic involvement on the

  20. Trophic and proliferative effects of Shh on motor neurons in embryonic spinal cord culture from wildtype and G93A SOD1 mice

    PubMed Central

    2013-01-01

    Background The developmental morphogen sonic hedgehog (Shh) may continue to play a trophic role in the support of terminally-differentiated motor neurons, of potential relevance to motor neuron disease. In addition, it may support the proliferation and differentiation of endogenous stem cells along motor neuronal lineages. As such, we have examined the trophic and proliferative effects of Shh supplementation or Shh antagonism in embryonic spinal cord cell cultures derived from wildtype or G93A SOD1 mice, a mouse model of amyotrophic lateral sclerosis. Results Shh supported survival, and stimulated growth of motor neurons, neurite outgrowth, and neurosphere formation in primary culture derived from both G93A SOD1 and WT mice. Shh increased the percentage of ciliated motor neurons, especially in G93A SOD1 culture. Shh-treated cultures showed increased neuronal proliferation compared to controls and especially cyclopamine treated cultures, from G93A SOD1 and WT mice. Moreover, Shh enhanced cell survival and differentiation of motor neuron precursors in WT culture. Conclusions Shh is neurotrophic to motor neurons and has mitogenic effects in WT and mSOD1 G93A culture in vitro. PMID:24119209

  1. Primary Teacher Identity, Commitment and Career in Performative School Cultures

    ERIC Educational Resources Information Center

    Troman, Geoff

    2008-01-01

    The research reported here maps changes in primary teachers' identity, commitment and perspectives and subjective experiences of occupational career in the context of performative primary school cultures. The research aimed to provide in-depth knowledge of performative school culture and teachers' subjective experiences in their work of teaching.…

  2. Self-modulation of primary motor cortex activity with motor and motor imagery tasks using real-time fMRI-based neurofeedback

    PubMed Central

    Berman, Brian D.; Horovitz, Silvina G.; Venkataraman, Gaurav; Hallett, Mark

    2011-01-01

    Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROIm) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROIm fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROIm during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROIm during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system. PMID:21803163

  3. Motor imagery beyond the motor repertoire: Activity in the primary visual cortex during kinesthetic motor imagery of difficult whole body movements.

    PubMed

    Mizuguchi, N; Nakata, H; Kanosue, K

    2016-02-19

    To elucidate the neural substrate associated with capabilities for kinesthetic motor imagery of difficult whole-body movements, we measured brain activity during a trial involving both kinesthetic motor imagery and action observation as well as during a trial with action observation alone. Brain activity was assessed with functional magnetic resonance imaging (fMRI). Nineteen participants imagined three types of whole-body movements with the horizontal bar: the giant swing, kip, and chin-up during action observation. No participant had previously tried to perform the giant swing. The vividness of kinesthetic motor imagery as assessed by questionnaire was highest for the chin-up, less for the kip and lowest for the giant swing. Activity in the primary visual cortex (V1) during kinesthetic motor imagery with action observation minus that during action observation alone was significantly greater in the giant swing condition than in the chin-up condition within participants. Across participants, V1 activity of kinesthetic motor imagery of the kip during action observation minus that during action observation alone was negatively correlated with vividness of the kip imagery. These results suggest that activity in V1 is dependent upon the capability of kinesthetic motor imagery for difficult whole-body movements. Since V1 activity is likely related to the creation of a visual image, we speculate that visual motor imagery is recruited unintentionally for the less vivid kinesthetic motor imagery of difficult whole-body movements. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Action Verbs and the Primary Motor Cortex: A Comparative TMS Study of Silent Reading, Frequency Judgments, and Motor Imagery

    ERIC Educational Resources Information Center

    Tomasino, Barbara; Fink, Gereon R.; Sparing, Roland; Dafotakis, Manuel; Weiss, Peter H.

    2008-01-01

    Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS[subscript M1] vs. TMS[subscript vertex]) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation…

  5. Action Verbs and the Primary Motor Cortex: A Comparative TMS Study of Silent Reading, Frequency Judgments, and Motor Imagery

    ERIC Educational Resources Information Center

    Tomasino, Barbara; Fink, Gereon R.; Sparing, Roland; Dafotakis, Manuel; Weiss, Peter H.

    2008-01-01

    Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area of the left primary motor cortex or, as a control, to the vertex (STIMULATION: TMS[subscript M1] vs. TMS[subscript vertex]) while right-handed volunteers silently read verbs related to hand actions. We examined three different tasks and time points for stimulation…

  6. Examining School Culture in Flemish and Chinese Primary Schools

    ERIC Educational Resources Information Center

    Zhu, Chang; Devos, Geert; Tondeur, Jo

    2014-01-01

    The aim of this research is to gain understanding about school culture characteristics of primary schools in the Flemish and Chinese context. The study was carried out in Flanders (Belgium) and China, involving a total of 44 Flemish schools and 40 Chinese schools. The School Culture Scales were used to measure five school culture dimensions with…

  7. Predicting Organizational Commitment from Organizational Culture in Turkish Primary Schools

    ERIC Educational Resources Information Center

    Ipek, Cemalettin

    2010-01-01

    This study aims to describe organizational culture and commitment and to predict organizational commitment from organizational culture in Turkish primary schools. Organizational Culture Scale (Ipek "1999") and Organizational Commitment Scale (Balay "2000") were used in the data gathering process. The data were collected from…

  8. Predicting Organizational Commitment from Organizational Culture in Turkish Primary Schools

    ERIC Educational Resources Information Center

    Ipek, Cemalettin

    2010-01-01

    This study aims to describe organizational culture and commitment and to predict organizational commitment from organizational culture in Turkish primary schools. Organizational Culture Scale (Ipek "1999") and Organizational Commitment Scale (Balay "2000") were used in the data gathering process. The data were collected from…

  9. Examining School Culture in Flemish and Chinese Primary Schools

    ERIC Educational Resources Information Center

    Zhu, Chang; Devos, Geert; Tondeur, Jo

    2014-01-01

    The aim of this research is to gain understanding about school culture characteristics of primary schools in the Flemish and Chinese context. The study was carried out in Flanders (Belgium) and China, involving a total of 44 Flemish schools and 40 Chinese schools. The School Culture Scales were used to measure five school culture dimensions with…

  10. Ventral Premotor to Primary Motor Cortical Interactions during Noxious and Naturalistic Action Observation

    ERIC Educational Resources Information Center

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Marquez, Gonzalo; Sanchez, Jose Andres; Ezquerro, Milagros; Giraldez, Manolo; Fernandez-del-Olmo, Miguel

    2010-01-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated…

  11. Form and Function in Motor Mimicry: Topographic Evidence that the Primary Function is Communicative.

    ERIC Educational Resources Information Center

    Bavelas, Janet Beavin; And Others

    1988-01-01

    Proposes that motor mimicry functions as a nonverbal, analogic, relationship message about similarity between observer and other, and that this message is encoded according to Gestalt principles of form. Concludes that the primary function of motor mimicry must be communicative and that any relationship to vicarious processes is secondary. (RAE)

  12. Ventral Premotor to Primary Motor Cortical Interactions during Noxious and Naturalistic Action Observation

    ERIC Educational Resources Information Center

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Marquez, Gonzalo; Sanchez, Jose Andres; Ezquerro, Milagros; Giraldez, Manolo; Fernandez-del-Olmo, Miguel

    2010-01-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated…

  13. Teaching Cultural History from Primary Events

    ERIC Educational Resources Information Center

    Carson, Robert N.

    2004-01-01

    This article explores the relationship between specific cultural events such as Galileo's work with the pendulum and a curriculum design that seeks to establish in skeletal form a comprehensive epic narrative about the co-evolution of cultural systems and human consciousness. The article explores some of the challenges and some of the strategies…

  14. Teaching Cultural History from Primary Events

    ERIC Educational Resources Information Center

    Carson, Robert N.

    2004-01-01

    This article explores the relationship between specific cultural events such as Galileo's work with the pendulum and a curriculum design that seeks to establish in skeletal form a comprehensive epic narrative about the co-evolution of cultural systems and human consciousness. The article explores some of the challenges and some of the strategies…

  15. How can ten fingers shape a pot? Evidence for equivalent function in culturally distinct motor skills.

    PubMed

    Gandon, Enora; Bootsma, Reinoud J; Endler, John A; Grosman, Leore

    2013-01-01

    Behavioural variability is likely to emerge when a particular task is performed in different cultural settings, assuming that part of human motor behaviour is influenced by culture. In analysing motor behaviour it is useful to distinguish how the action is performed from the result achieved. Does cultural environment lead to specific cultural motor skills? Are there differences between cultures both in the skills themselves and in the corresponding outcomes? Here we analyse the skill of pottery wheel-throwing in French and Indian cultural environments. Our specific goal was to examine the ability of expert potters from distinct cultural settings to reproduce a common model shape (a sphere). The operational aspects of motor performance were captured through the analysis of the hand positions used by the potters during the fashioning process. In parallel, the outcomes were captured by the geometrical characteristics of the vessels produced. As expected, results revealed a cultural influence on the operational aspects of the potters' motor skill. Yet, the marked cultural differences in hand positions used did not give rise to noticeable differences in the shapes of the vessels produced. Hence, for the simple model form studied, the culturally-specific motor traditions of the French and Indian potters gave rise to an equivalent outcome, that is shape uniformity. Further work is needed to test whether such equivalence is also observed in more complex ceramic shapes.

  16. How Can Ten Fingers Shape a Pot? Evidence for Equivalent Function in Culturally Distinct Motor Skills

    PubMed Central

    Gandon, Enora; Bootsma, Reinoud J.; Endler, John A.; Grosman, Leore

    2013-01-01

    Behavioural variability is likely to emerge when a particular task is performed in different cultural settings, assuming that part of human motor behaviour is influenced by culture. In analysing motor behaviour it is useful to distinguish how the action is performed from the result achieved. Does cultural environment lead to specific cultural motor skills? Are there differences between cultures both in the skills themselves and in the corresponding outcomes? Here we analyse the skill of pottery wheel-throwing in French and Indian cultural environments. Our specific goal was to examine the ability of expert potters from distinct cultural settings to reproduce a common model shape (a sphere). The operational aspects of motor performance were captured through the analysis of the hand positions used by the potters during the fashioning process. In parallel, the outcomes were captured by the geometrical characteristics of the vessels produced. As expected, results revealed a cultural influence on the operational aspects of the potters’ motor skill. Yet, the marked cultural differences in hand positions used did not give rise to noticeable differences in the shapes of the vessels produced. Hence, for the simple model form studied, the culturally-specific motor traditions of the French and Indian potters gave rise to an equivalent outcome, that is shape uniformity. Further work is needed to test whether such equivalence is also observed in more complex ceramic shapes. PMID:24312327

  17. Somatotopic mapping of the human primary sensorimotor cortex during motor imagery and motor execution by functional magnetic resonance imaging.

    PubMed

    Stippich, Christoph; Ochmann, Henrik; Sartor, Klaus

    2002-10-04

    The human primary sensorimotor cortex was investigated for somatotopic organization during motor imagery (IM) which was compared to motor execution (EM). Block designed BOLD (blood oxygen level dependent)-functional magnetic resonance imaging at 1.5 Tesla was applied in 14 right handed volunteers during imagined and executed tongue, finger and toe movements. BOLD-clusters were assessed for anatomically correct sensorimotor localization. Euklidian coordinates, relative signal change and correlation to the applied reference function were determined. Statistical means were calculated. IM recruited somatotopically organized primary sensorimotor representations of the precentral gyrus that reflected the homunculus and overlapped in part with EM representations. Mean BOLD-signals ranged from 1.93 to 3.18% for EM, and from 0.73 to 1.47% for IM. The results support the hypothesis that the primary sensorimotor cortex is active during IM and that IM and EM share common functional circuits.

  18. Complementary activation of the ipsilateral primary motor cortex during a sustained handgrip task.

    PubMed

    Shibuya, Kenichi; Kuboyama, Naomi; Yamada, Seigo

    2016-01-01

    Near-infrared spectroscopy (NIRS) can be used to examine bilateral motor cortex activation during a sustained motor task in brain areas where increased oxygenation reflects cortical activation. This study examines the time course of activation of the bilateral motor cortex during a moderate-intensity handgrip task. Ten healthy right-handed male subjects participated in this study. Functional NIRS probes were placed over the cortex to measure motor cortical activations while the subjects performed a 180-s handgrip task incrementally [30-60% of the maximal voluntary contraction (MVC) at 0.17% increase/s] Contralateral primary motor cortex (ContraM1) oxygenation values significantly increased from baseline between 40 and 120 s after the start of the motor task (p < 0.05). Moreover, the ipsilateral primary motor cortex (IpsiM1) oxygenation values significantly increased from baseline between 140 and 180 s after the start of the motor task (p < 0.05). IpsiM1 oxygenation gradually increased from 140 to 180 s, whereas ContraM1 oxygenation gradually decreased from 120 to 180 s after the start of the motor task. These results suggest that the complementary functions of IpsiM1 become activated in response to the working of the ContraM1 during a continuous handgrip task.

  19. Cross-cultural validity of standardized motor development screening and assessment tools: a systematic review.

    PubMed

    Mendonça, Bianca; Sargent, Barbara; Fetters, Linda

    2016-12-01

    To investigate whether standardized motor development screening and assessment tools that are used to evaluate motor abilities of children aged 0 to 2 years are valid in cultures other than those in which the normative sample was established. This was a systematic review in which six databases were searched. Studies were selected based on inclusion/exclusion criteria and appraised for evidence level and quality. Study variables were extracted. Twenty-three studies representing six motor development screening and assessment tools in 16 cultural contexts met the inclusion criteria: Alberta Infant Motor Scale (n=7), Ages and Stages Questionnaire, 3rd edition (n=2), Bayley Scales of Infant and Toddler Development, 3rd edition (n=8), Denver Developmental Screening Test, 2nd edition (n=4), Harris Infant Neuromotor Test (n=1), and Peabody Developmental Motor Scales, 2nd edition (n=1). Thirteen studies found significant differences between the cultural context and normative sample. Two studies established reliability and/or validity of standardized motor development assessments in high-risk infants from different cultural contexts. Five studies established new population norms. Eight studies described the cross-cultural adaptation of a standardized motor development assessment. Standardized motor development assessments have limited validity in cultures other than that in which the normative sample was established. Their use can result in under- or over-referral for services. © 2016 Mac Keith Press.

  20. Different Effects of Implicit and Explicit Motor Sequence Learning on Latency of Motor Evoked Potential Evoked by Transcranial Magnetic Stimulation on the Primary Motor Cortex

    PubMed Central

    Hirano, Masato; Kubota, Shinji; Koizume, Yoshiki; Tanaka, Shinya; Funase, Kozo

    2017-01-01

    Motor training induces plastic changes in the primary motor cortex (M1). However, it is unclear whether and how the latency of motor-evoked potentials (MEP) and MEP amplitude are affected by implicit and/or explicit motor learning. Here, we investigated the changes in M1 excitability and MEP latency induced by implicit and explicit motor learning. The subjects performed a serial reaction time task (SRTT) with their five fingers. In this task, visual cues were lit up sequentially along with a predetermined order. Through training, the subjects learned the order of sequence implicitly and explicitly. Before and after the SRTT, we recorded MEP at 25 stimulation points around the hot spot for the flexor pollicis brevis (FPB) muscle. Although no changes in MEP amplitude were observed in either session, we found increases in MEP latency and changes in histogram of MEP latency after implicit learning. Our results suggest that reorganization across the motor cortices occurs during the acquisition of implicit knowledge. In contrast, acquisition of explicit knowledge does not appear to induce the reorganization based on the measures we recorded. The fact that the above mentioned increases in MEP latency occurred without any alterations in MEP amplitude suggests that learning has different effects on different physiological signals. In conclusion, our results propose that analyzing a combination of some indices of M1 excitability, such as MEP amplitude and MEP latency, is encouraged in order to understand plasticity across motor cortices. PMID:28101014

  1. Different Effects of Implicit and Explicit Motor Sequence Learning on Latency of Motor Evoked Potential Evoked by Transcranial Magnetic Stimulation on the Primary Motor Cortex.

    PubMed

    Hirano, Masato; Kubota, Shinji; Koizume, Yoshiki; Tanaka, Shinya; Funase, Kozo

    2016-01-01

    Motor training induces plastic changes in the primary motor cortex (M1). However, it is unclear whether and how the latency of motor-evoked potentials (MEP) and MEP amplitude are affected by implicit and/or explicit motor learning. Here, we investigated the changes in M1 excitability and MEP latency induced by implicit and explicit motor learning. The subjects performed a serial reaction time task (SRTT) with their five fingers. In this task, visual cues were lit up sequentially along with a predetermined order. Through training, the subjects learned the order of sequence implicitly and explicitly. Before and after the SRTT, we recorded MEP at 25 stimulation points around the hot spot for the flexor pollicis brevis (FPB) muscle. Although no changes in MEP amplitude were observed in either session, we found increases in MEP latency and changes in histogram of MEP latency after implicit learning. Our results suggest that reorganization across the motor cortices occurs during the acquisition of implicit knowledge. In contrast, acquisition of explicit knowledge does not appear to induce the reorganization based on the measures we recorded. The fact that the above mentioned increases in MEP latency occurred without any alterations in MEP amplitude suggests that learning has different effects on different physiological signals. In conclusion, our results propose that analyzing a combination of some indices of M1 excitability, such as MEP amplitude and MEP latency, is encouraged in order to understand plasticity across motor cortices.

  2. Functional magnetic resonance imaging of the primary motor cortex in humans: response to increased functional demands.

    PubMed

    Khushu, S; Kumaran, S S; Tripathi, R P; Gupta, A; Jain, P C; Jain, V

    2001-06-01

    Functional magnetic resonance imaging (fMRI) studies have been performed on 20 right handed volunteers at 1.5 Tesla using echo planar imaging (EPI) protocol. Index finger tapping invoked localized activation in the primary motor area. Consistent and highly reproducible activation in the primary motor area was observed in six different sessions of a volunteer over a period of one month. Increased tapping rate resulted in increase in the blood oxygenation level dependent (BOLD) signal intensity as well as the volume/area of activation (pixels) in the contralateral primary motor area up to tapping rate of 120 taps/min (2 Hz), beyond which it saturates. Activation in supplementary motor area was also observed. The obtained results are correlated to increased functional demands.

  3. tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: A 7 T magnetic resonance spectroscopy study

    PubMed Central

    Kim, Soyoung; Stephenson, Mary C.; Morris, Peter G.; Jackson, Stephen R.

    2014-01-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and ‘supervised’ learning of internal ‘forward’ models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task. PMID:24904994

  4. tDCS-induced alterations in GABA concentration within primary motor cortex predict motor learning and motor memory: a 7 T magnetic resonance spectroscopy study.

    PubMed

    Kim, Soyoung; Stephenson, Mary C; Morris, Peter G; Jackson, Stephen R

    2014-10-01

    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability in a polarity specific manner and has been shown to influence learning and memory. tDCS may have both on-line and after-effects on learning and memory, and the latter are thought to be based upon tDCS-induced alterations in neurochemistry and synaptic function. We used ultra-high-field (7 T) magnetic resonance spectroscopy (MRS), together with a robotic force adaptation and de-adaptation task, to investigate whether tDCS-induced alterations in GABA and Glutamate within motor cortex predict motor learning and memory. Note that adaptation to a robot-induced force field has long been considered to be a form of model-based learning that is closely associated with the computation and 'supervised' learning of internal 'forward' models within the cerebellum. Importantly, previous studies have shown that on-line tDCS to the cerebellum, but not to motor cortex, enhances model-based motor learning. Here we demonstrate that anodal tDCS delivered to the hand area of the left primary motor cortex induces a significant reduction in GABA concentration. This effect was specific to GABA, localised to the left motor cortex, and was polarity specific insofar as it was not observed following either cathodal or sham stimulation. Importantly, we show that the magnitude of tDCS-induced alterations in GABA concentration within motor cortex predicts individual differences in both motor learning and motor memory on the robotic force adaptation and de-adaptation task. Copyright © 2014. Published by Elsevier Inc.

  5. Anodal tDCS over the primary motor cortex improves motor imagery benefits on postural control: A pilot study.

    PubMed

    Saruco, Elodie; Rienzo, Franck Di; Nunez-Nagy, Susana; Rubio-Gonzalez, Miguel A; Jackson, Philip L; Collet, Christian; Saimpont, Arnaud; Guillot, Aymeric

    2017-03-28

    Performing everyday actions requires fine postural control, which is a major focus of functional rehabilitation programs. Among the various range of training methods likely to improve balance and postural stability, motor imagery practice (MIP) yielded promising results. Transcranial direct current stimulation (tDCS) applied over the primary motor cortex was also found to potentiate the benefits of MIP on upper-limb motor tasks. Yet, combining both techniques has not been tested for tasks requiring fine postural control. To determine the impact of MIP and the additional effects of tDCS, 14 participants performed a postural control task before and after two experimental (MIP + anodal or sham tDCS over the primary motor cortex) and one control (control task + sham tDCS) conditions, in a double blind randomized study. Data revealed a significant decrease of the time required to perform the postural task. Greater performance gains were recorded when MIP was paired with anodal tDCS and when the task involved the most complex postural adjustments. Altogether, findings highlight short-term effects of MIP on postural control and suggest that combining MIP with tDCS might also be effective in rehabilitation programs for regaining postural skills in easily fatigable persons and neurologic populations.

  6. The Neural Mechanism Exploration of Adaptive Motor Control: Dynamical Economic Cell Allocation in the Primary Motor Cortex.

    PubMed

    Li, Wei; Guo, Yangyang; Fan, Jing; Ma, Chaolin; Ma, Xuan; Chen, Xi; He, Jiping

    2016-06-14

    Adaptive flexibility is of significance for the smooth and efficient movements in goal attainment. However, the underlying work mechanism of the cerebral cortex in adaptive motor control still remains unclear. How does the cerebral cortex organize and coordinate the activity of a large population of cells in the implementation of various motor strategies? To explore this issue, single-unit activities from the M1 region and kinematic data were recorded simultaneously in monkeys performing 3D reach-to-grasp tasks with different perturbations. Varying motor control strategies were employed and achieved in different perturbed tasks, via the dynamic allocation of cells to modulate specific movement parameters. An economic principle was proposed for the first time to describe a basic rule for cell allocation in the primary motor cortex. This principle, defined as the Dynamic Economic Cell Allocation Mechanism (DECAM), guarantees benefit maximization in cell allocation under limited neuronal resources, and avoids committing resources to uneconomic investments for unreliable factors with no or little revenue. That is to say, the cells recruited are always preferentially allocated to those factors with reliable return; otherwise, the cells are dispatched to respond to other factors about task. The findings of this study might partially reveal the working mechanisms underlying the role of the cerebral cortex in adaptive motor control, wherein is also of significance for the design of future intelligent brain-machine interfaces and rehabilitation device.

  7. Motor Training Promotes Both Synaptic and Intrinsic Plasticity of Layer II/III Pyramidal Neurons in the Primary Motor Cortex

    PubMed Central

    Kida, Hiroyuki; Tsuda, Yasumasa; Ito, Nana; Yamamoto, Yui; Owada, Yuji; Kamiya, Yoshinori; Mitsushima, Dai

    2016-01-01

    Motor skill training induces structural plasticity at dendritic spines in the primary motor cortex (M1). To further analyze both synaptic and intrinsic plasticity in the layer II/III area of M1, we subjected rats to a rotor rod test and then prepared acute brain slices. Motor skill consistently improved within 2 days of training. Voltage clamp analysis showed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate (AMPA/NMDA) ratios and miniature EPSC amplitudes in 1-day trained rats compared with untrained rats, suggesting increased postsynaptic AMPA receptors in the early phase of motor learning. Compared with untrained controls, 2-days trained rats showed significantly higher miniature EPSC amplitude and frequency. Paired-pulse analysis further demonstrated lower rates in 2-days trained rats, suggesting increased presynaptic glutamate release during the late phase of learning. One-day trained rats showed decreased miniature IPSC frequency and increased paired-pulse analysis of evoked IPSC, suggesting a transient decrease in presynaptic γ-aminobutyric acid (GABA) release. Moreover, current clamp analysis revealed lower resting membrane potential, higher spike threshold, and deeper afterhyperpolarization in 1-day trained rats—while 2-days trained rats showed higher membrane potential, suggesting dynamic changes in intrinsic properties. Our present results indicate dynamic changes in glutamatergic, GABAergic, and intrinsic plasticity in M1 layer II/III neurons after the motor training. PMID:27193420

  8. 9 CFR 3.114 - Primary conveyances (motor vehicle, rail, air and marine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., rail, air and marine). 3.114 Section 3.114 Animals and Animal Products ANIMAL AND PLANT HEALTH... conveyances (motor vehicle, rail, air and marine). (a) The animal cargo space of primary conveyances used in.... (e) The interiors of animal cargo spaces in primary conveyances must be kept clean. (f) Live...

  9. 9 CFR 3.114 - Primary conveyances (motor vehicle, rail, air and marine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., rail, air and marine). 3.114 Section 3.114 Animals and Animal Products ANIMAL AND PLANT HEALTH... conveyances (motor vehicle, rail, air and marine). (a) The animal cargo space of primary conveyances used in.... (e) The interiors of animal cargo spaces in primary conveyances must be kept clean. (f) Live...

  10. 9 CFR 3.114 - Primary conveyances (motor vehicle, rail, air and marine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Primary conveyances (motor vehicle, rail, air and marine). 3.114 Section 3.114 Animals and Animal Products ANIMAL AND PLANT HEALTH..., Care, Treatment, and Transportation of Marine Mammals Transportation Standards § 3.114 Primary...

  11. Motor Profile of Portuguese Preschool Children on the Peabody Developmental Motor Scales-2: A Cross-Cultural Study

    ERIC Educational Resources Information Center

    Saraiva, Linda; Rodrigues, Luis P.; Cordovil, Rita; Barreiros, Joao

    2013-01-01

    This study was designed to examine the cultural sensitivity of the PDMS-2 for Portuguese preschool children aged 36-71 months. A total of 540 children (255 males and 285 females) from 15 public preschools of Viana do Castelo, Portugal, were assessed. Age and gender effects in motor performance were examined. Results indicated that PDMS-2 is valid…

  12. Motor Profile of Portuguese Preschool Children on the Peabody Developmental Motor Scales-2: A Cross-Cultural Study

    ERIC Educational Resources Information Center

    Saraiva, Linda; Rodrigues, Luis P.; Cordovil, Rita; Barreiros, Joao

    2013-01-01

    This study was designed to examine the cultural sensitivity of the PDMS-2 for Portuguese preschool children aged 36-71 months. A total of 540 children (255 males and 285 females) from 15 public preschools of Viana do Castelo, Portugal, were assessed. Age and gender effects in motor performance were examined. Results indicated that PDMS-2 is valid…

  13. Intersections between interprofessional practice, cultural competency and primary healthcare.

    PubMed

    Oelke, Nelly D; Thurston, Wilfreda E; Arthur, Nancy

    2013-09-01

    The concepts of interprofessional collaborative practice (IPCP), cultural competency and primary healthcare (PHC) appear to be linked in theory and practice. This discussion article provides arguments explicating the potential linkages between IPCP and cultural competency. We argue that cultural competency is an important component of IPCP both for relationships with patients and/or communities in which providers work and between team members. Organizational structures also play an important role in facilitating IPCP and cultural competency. The integration of both IPCP and cultural competency has the potential to enhance positive health outcomes. Furthermore, we argue IPCP and cultural competency have important implications for PHC service design, given interprofessional teams are a key component of PHC systems. Linking these concepts in providing PHC services can be essential for impacting outcomes at all levels of primary healthcare, including patient, provider and systems.

  14. Grounding Signs of Culture: Primary Intersubjectivity in Social Semiosis

    ERIC Educational Resources Information Center

    Cowley, Stephen J.; Moodley, Sheshni; Fiori-Cowley, Agnese

    2004-01-01

    The article examines how infants are first permeated by culture. Building on Thibault (2000), semiogenesis is traced to the joint activity of primary intersubjectivity. Using an African example, analysis shows how--at 14 weeks--an infant already uses culturally specific indicators of "what a caregiver wants." Human predispositions and…

  15. Grounding Signs of Culture: Primary Intersubjectivity in Social Semiosis

    ERIC Educational Resources Information Center

    Cowley, Stephen J.; Moodley, Sheshni; Fiori-Cowley, Agnese

    2004-01-01

    The article examines how infants are first permeated by culture. Building on Thibault (2000), semiogenesis is traced to the joint activity of primary intersubjectivity. Using an African example, analysis shows how--at 14 weeks--an infant already uses culturally specific indicators of "what a caregiver wants." Human predispositions and…

  16. A case of presumptive primary lateral sclerosis with upper and lower motor neurone pathology.

    PubMed

    Short, Cathy L; Scott, Grace; Blumbergs, Peter C; Koblar, Simon A

    2005-08-01

    Motor Neurone Disease (MND) is one of the commonest neurodegenerative disorders of adulthood. MND characteristically presents with a combination of both upper and lower motor neurone features. Primary Lateral Sclerosis (PLS) is thought to be a variant of MND presenting with purely upper motor neurone signs. Debate continues over whether PLS constitutes a distinct pathological entity or whether it is part of the spectrum of motor neurone diseases that present as an upper motor neurone-predominant form of MND. We present a case of MND with purely upper motor neurone features and a prominent pain component. A pre-mortem diagnosis of PLS was made, however autopsy findings demonstrated both upper and lower motor neurone involvement. We believe these findings support the view that PLS is not a discrete pathological entity, but that it is a part of the range of motor neurone diseases that present with predominant but not exclusive upper motor neurone involvement. This case also highlights the feature that pain may be associated with MND even though it is not appreciated to have a sensory pathology.

  17. Methylmalonate toxicity in primary neuronal cultures.

    PubMed

    McLaughlin, B A; Nelson, D; Silver, I A; Erecinska, M; Chesselet, M F

    1998-09-01

    Several inhibitors of mitochondrial complex II cause neuronal death in vivo and in vitro. The goal of the present work was to characterize in vitro the effects of malonate (a competitive blocker of the complex) which induces neuronal death in a pattern similar to that seen in striatum in Huntington's disease. Exposure of striatal and cortical cultures from embryonic rat brain for 24 h to methylmalonate, a compound which produces malonate intracellularly, led to a dose-dependent cell death. Methylmalonate (10 mM) caused >90% mortality of neurons although cortical cells were unexpectedly more vulnerable. Cell death was attenuated in a medium containing antioxidants. Further characterization revealed that DNA laddering could be detected after 3 h of treatment. Morphological observations (videomicroscopy and Hoechst staining) showed that both necrotic and apoptotic cell death occurred in parallel; apoptosis was more prevalent. A decrease in the ATP/ADP ratio was observed after 3 h of treatment with 10 mM methylmalonate. In striatal cultures it occurred concomitantly with a decline in GABA and a rise in aspartate content and the aspartate/glutamate ratio. Changes in ion concentrations were measured in similar cortical cultures from mouse brain. Neuronal [Na+]i increased while [K+]i and membrane potential decreased after 20 min of continuous incubation in 10 mM methylmalonate. These changes progressed with time, and a rise in [Ca2+]i was also observed after 1 h. The results demonstrate that malonate collapses cellular ion gradients, restoration of which imposes an additional load on the already compromised ATP-generation machinery. An early elevation in [Ca2+]i may trigger an increase in activity of proteases, lipases and endonucleases and production of free radicals and DNA damage which, ultimately, leads to cells death. The data also suggest that maturational and/or extrinsic factors are likely to be critical for the increased vulnerability of striatal neurons to

  18. Primary cell culture of human adenocarcinomas--practical considerations.

    PubMed

    Lerescu, Lucian; Tucureanu, Cătălin; Caraş, Iuliana; Neagu, Stefan; Melinceanu, Laura; Sălăgeanu, Aurora

    2008-01-01

    Cell culture is one of the major tools for oncology research, being an excellent system in which to study the biochemistry and molecular biology associated with individual cancer types and to understand cancer cell physiology. Progress in understanding the biology of any type of carcinoma has been impeded by the inability to culture adequately malignant cells from most epithelial tissues. The ultimate in vitro tumor model would completely reflect the in vivo tumor microenvironment in function and mechanism. Unfortunately, such a model does not currently exist. Homogeneous cell lines that can be continuously propagated on plastic surfaces have been extensively used as a surrogate for tumor environment; however they are very different from the in vivo tumor cells. Model systems involving primary culture represent the situation most closely related to the original tissue although they have a number of disadvantages over cell lines, such as the limited ability to repeat studies with a well characterized culture system that can be used in multiple laboratories. The primary culture may contain many types of stromal and infiltrating cell types potentially complicating the interpretation of data. Yet, their properties better reflect the cellular interactions present in intact tissue. The present article reviews the critical steps in obtaining, routine maintenance and cryopreservation of primary tumor cell cultures, based on information from literature and personal experience on the subject. The article also includes an updated protocol for primary tumor cell isolation and culture.

  19. The Relationship between Social and Motor Cognition in Primary School Age-Children

    PubMed Central

    Kenny, Lorcan; Hill, Elisabeth; Hamilton, Antonia F. de C.

    2016-01-01

    There is increased interest in the relationship between motor skills and social skills in child development, with evidence that the mechanisms underlying these behaviors may be linked. We took a cognitive approach to this problem, and examined the relationship between four specific cognitive domains: theory of mind, motor skill, action understanding, and imitation. Neuroimaging and adult research suggest that action understanding and imitation are closely linked, but are somewhat independent of theory of mind and low-level motor control. Here, we test if a similar pattern is shown in child development. A sample of 101 primary school aged children with a wide ability range completed tests of IQ (Raven’s matrices), theory of mind, motor skill, action understanding, and imitation. Parents reported on their children’s social, motor and attention performance as well as developmental concerns. The results showed that action understanding and imitation correlate, with the latter having a weak link to motor control. Theory of mind was independent of the other tasks. These results imply that independent cognitive processes for social interaction (theory of mind) and for motor control can be identified in primary school age children, and challenge approaches that link all these domains together. PMID:26941685

  20. Absent movement-related cortical potentials in children with primary motor stereotypies.

    PubMed

    Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A; Vorbach, Sherry; Singer, Harvey S; Hallett, Mark

    2014-08-01

    The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown, with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about 1 second before the onset of a voluntary movement. Early MRCPs preceded self-paced arm movements in 8 of 10 children with motor stereotypies and in 6 of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. © 2013 International Parkinson and Movement Disorder Society.

  1. Absent movement-related cortical potentials in children with primary motor stereotypies

    PubMed Central

    Houdayer, Elise; Walthall, Jessica; Belluscio, Beth A.; Vorbach, Sherry; Singer, Harvey S.; Hallett, Mark

    2013-01-01

    Background The underlying pathophysiologic mechanism for complex motor stereotypies in children is unknown with hypotheses ranging from an arousal to a motor control disorder. Movement-related cortical potentials (MRCPs), representing the activation of cerebral areas involved in the generation of movements, precede and accompany self-initiated voluntary movements. The goal of this study was to compare cerebral activity associated with stereotypies to that seen with voluntary movements in children with primary complex motor stereotypies. Methods Electroencephalographic (EEG) activity synchronized with video recording was recorded in 10 children diagnosed with primary motor stereotypies and 7 controls. EEG activity related to stereotypies and self-paced arm movements were analyzed for presence or absence of early or late MRCP, a steep negativity beginning about one second before the onset of a voluntary movement. Results Early MRCPs preceded self-paced arm movements in 8 out of 10 children with motor stereotypies and in 6 out of 7 controls. Observed MRCPs did not differ between groups. No MRCP was identified before the appearance of a complex motor stereotypy. Conclusions Unlike voluntary movements, stereotypies are not preceded by MRCPs. This indicates that premotor areas are likely not involved in the preparation of these complex movements and suggests that stereotypies are initiated by mechanisms different from voluntary movements. Further studies are required to determine the site of the motor control abnormality within cortico-striatal-thalamo-cortical pathways and to identify whether similar findings would be found in children with secondary stereotypies. PMID:24259275

  2. Relevant principal factors affecting the reproducibility of insect primary culture.

    PubMed

    Ogata, Norichika; Iwabuchi, Kikuo

    2017-02-22

    The primary culture of insect cells often suffers from problems with poor reproducibility in the quality of the final cell preparations. The cellular composition of the explants (cell number and cell types), surgical methods (surgical duration and surgical isolation), and physiological and genetic differences between donors may be critical factors affecting the reproducibility of culture. However, little is known about where biological variation (interindividual differences between donors) ends and technical variation (variance in replication of culture conditions) begins. In this study, we cultured larval fat bodies from the Japanese rhinoceros beetle, Allomyrina dichotoma, and evaluated, using linear mixed models, the effect of interindividual variation between donors on the reproducibility of the culture. We also performed transcriptome analysis of the hemocyte-like cells mainly seen in the cultures using RNA sequencing and ultrastructural analyses of hemocytes using a transmission electron microscope, revealing that the cultured cells have many characteristics of insect hemocytes.

  3. Non-primary motor areas in the human frontal lobe are connected directly to hand muscles.

    PubMed

    Teitti, S; Määttä, S; Säisänen, L; Könönen, M; Vanninen, R; Hannula, H; Mervaala, E; Karhu, J

    2008-04-15

    Structural studies in primates have shown that, in addition to the primary motor cortex (M1), premotor areas are a source of corticospinal tracts. The function of these putative corticospinal neuronal tracts in humans is still unclear. We found frontal non-primary motor areas (NPMAs), which react to targeted non-invasive magnetic pulses and activate peripheral muscles as fast as or even faster than those in M1. Hand muscle movements were observed in all our subjects about 20 ms after transcranial stimulation of the superior frontal gyrus (Brodmann areas 6 and 8). Stimulation of NPMA could activate both proximal and distal upper limb muscles with the same delay as a stimulation of the M1, indicating converging motor representations with direct functional connections to the hand. We suggest that these non-primary cortical motor representations provide additional capacity for the fast execution of movements. Such a capacity may play a role in motor learning and in recovery from motor deficits.

  4. Continuous theta-burst stimulation of the primary motor cortex in essential tremor.

    PubMed

    Hellriegel, Helge; Schulz, Eva M; Siebner, Hartwig R; Deuschl, Günther; Raethjen, Jan H

    2012-05-01

    We investigated whether essential tremor (ET) can be altered by suppressing the corticospinal excitability in the primary motor cortex (M1) with transcranial magnetic stimulation. 10 Patients with ET and 10 healthy controls underwent transcranial continuous theta-burst stimulation (cTBS) of the left primary motor hand area at 80% (real cTBS) and 30% (control cTBS) of active motor threshold in two separate sessions at least one week apart. Postural tremor was rated clinically and measured accelerometrically before and after cTBS. Corticospinal excitability was assessed by recording the motor evoked potentials (MEP) from the first dorsal interosseous muscle. Real cTBS but not control cTBS reduced the tremor total power assessed with accelerometry. This beneficial effect was subclinical as there were no significant changes in clinical tremor rating after real cTBS. Relative to control cTBS, real cTBS reduced corticospinal excitability in the stimulated primary motor cortex only in healthy controls but not in ET patients. Real cTBS has a beneficial effect on ET. Since cTBS did not induce a parallel reduction in corticospinal excitability, this effect was not mediated by a suppression of the corticospinal motor output. "Inhibitory" cTBS of M1 leads to a consistent but subclinical reduction in tremor amplitude. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. N-cadherin regulates primary motor axons growth and branching during zebrafish embryonic development

    PubMed Central

    Brusés, Juan L

    2013-01-01

    N-cadherin is a classical type I cadherin that contributes to the formation of neural circuits by regulating growth cone migration and the formation of synaptic contacts. This study analyzed the role of N-cadherin in primary motor axons growth during development of the zebrafish (Danio rerio) embryo. After exiting the spinal cord, primary motor axons migrate ventrally through a common pathway and form the first neuromuscular junction with the muscle pioneer cells located at the horizontal myoseptum, which serves as a choice point for cell-type specific pathway selection. Analysis of N-cadherin mutants (cdh2hi3644Tg) and embryos injected with N-cadherin antisense morpholinos showed primary motor axons extending aberrant axonal branches at the choice point in ~40% of the somitic hemisegments, and an ~150% increase in the number of branches per axon length within the ventral myotome. Analysis of individual axons trajectories showed that the caudal (CaP) and rostral (RoP) motor neurons axons formed aberrant branches at the choice point which abnormally extended in the rostrocaudal axis and ventrally to the horizontal myoseptum. Expression of a dominant-interfering N-cadherin cytoplasmic domain in primary motor neurons caused some axons to abnormally stall at the horizontal myoseptum and to impair their migration into the ventral myotome. However, in N-cadherin depleted embryos the majority of primary motor axons innervated their appropriate myotomal territories indicating that N-cadherin regulates motor axon growth and branching without severely affecting the mechanisms that control axonal target selection. PMID:21452216

  6. Isolation, Purification, and Culture of Primary Murine Sensory Neurons

    PubMed Central

    Katzenell, Sarah; Cabrera, Jorge R.; North, Brian J.; Leib, David A.

    2017-01-01

    Cultured primary neurons have been of extraordinary value for the study of neuronal anatomy, cell biology, and physiology. While use of neuronal cell lines has ease and utility, there are often caveats that arise due to their mitotic nature. This methods article presents detailed methodology for the preparation, purification, and culture of adult murine sensory neurons for the study of herpes simplex virus lytic and latent infections. While virology is the application for our laboratory, these cultures also have broad utility for neurobiologists and cell biologists. While these primary cultures have been highly informative, the methodology is challenging to many investigators. Through publication of this highly detailed protocol, it is our hope that the use of this culture system can spread in the field to allow more rapid progress in furthering our understanding of neurotropic virus infection. PMID:28808974

  7. Effects of motor training on the recovery of manual dexterity after primary motor cortex lesion in macaque monkeys.

    PubMed

    Murata, Yumi; Higo, Noriyuki; Oishi, Takao; Yamashita, Akiko; Matsuda, Keiji; Hayashi, Motoharu; Yamane, Shigeru

    2008-02-01

    To investigate the effects of postlesion training on motor recovery, we compared the motor recovery of macaque monkeys that had received intensive motor training with those that received no training after a lesion of the primary motor cortex (M1). An ibotenic acid lesion in the M1 digit area resulted in impairment of hand function, with complete loss of digit movement. In the monkeys that had undergone intensive daily training (1 h/day, 5 days/wk) after the lesion, behavioral indexes used to evaluate manual dexterity recovered to the same level as in the prelesion period after 1 or 2 mo of postlesion training period. Relatively independent digit movements, including precision grip (prehension of a small object with finger-to-thumb opposition), were restored in the trained monkeys. Although the behavioral indexes of manual dexterity recovered to some extent in the monkeys without the postlesion training, they remained lower than those in the prelesion period until several months after M1 lesion. The untrained monkeys frequently used alternate grip strategies to grasp a small object with the affected hand, holding food pellets between the tip of the index finger and the dorsum of the thumb. These results suggest that the recovery after M1 lesion includes both use-dependent and use-independent processes and that the recovery of precision grip can be promoted by intensive use of the affected hand in postlesion training.

  8. Brain responses to handwritten and printed letters differentially depend on the activation state of the primary motor cortex.

    PubMed

    Wamain, Yannick; Tallet, Jessica; Zanone, Pier-Giorgio; Longcamp, Marieke

    2012-11-15

    Previous studies demonstrated that visual perception of handwritten letters activates the left primary motor cortex more strongly than printed letters. Here, we used EEG to record cortical responses evoked by single letters to directly test if their visual processing is actually influenced by their motor content. We manipulated the "motor familiarity" of letters that we considered high for letters written by the observers themselves, medium for letters written by other individuals, and low for printed, machine designed letters. In order to relate the effects of motor familiarity to the activation of the primary motor cortex, we also directly manipulated its availability during the visual task: we computed Event-Related Potentials (ERPs) over the posterior cortex during a dual task where participants had to observe the letters while performing unrelated self-paced brief movements of the right hand approximately every 5s (allowing the primary motor cortex to successively activate and "idle"). At 300-350 ms and 500-600 ms after stimulus onset, the amplitude of the ERP components markedly reflected the level of motor familiarity of the observed letter. Nonetheless, this was true only when the primary motor cortex was in an "idling" state: when the motor cortex was in an activation state, this motor familiarity effect was dropped. This clearly indicates that, at these latencies, the motor information embedded in letters is processed in the brain and that this processing depends on the activation state of the left primary motor cortex. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Motor Development in 9-Month-Old Infants in Relation to Cultural Differences and Iron Status

    PubMed Central

    Schapiro, Lauren; Liang, Weilang; Rodrigues, Onike; Shafir, Tal; Kaciroti, Niko; Jacobson, Sandra W.; Lozoff, Betsy

    2011-01-01

    Motor development, which allows infants to explore their environment, promoting cognitive, social, and perceptual development, can be influenced by cultural practices and nutritional factors, such as iron deficiency. This study compared fine and gross motor development in 209 9-month-old infants from urban areas of China, Ghana, and USA (African-Americans) and considered effects of iron status. Iron deficiency anemia was most common in the Ghana sample (55%) followed by USA and China samples. Controlling for iron status, Ghanaian infants displayed precocity in gross motor development and most fine-motor reach-and-grasp tasks. US African-Americans performed the poorest in all tasks except bimanual coordination and the large ball. Controlling for cultural site, iron status showed linear trends for gross motor milestones and fine motor skills with small objects. Our findings add to the sparse literature on infant fine motor development across cultures. The results also indicate the need to consider nutritional factors when examining cultural differences in infant development. PMID:21298634

  10. Encoding of Coordinated Grasp Trajectories in Primary Motor Cortex

    PubMed Central

    Takahashi, Kazutaka; Amit, Yali; Hatsopoulos, Nicholas G.

    2011-01-01

    Few studies have investigated how the cortex encodes the pre-shaping of the hand as an object is grasped, an ethological movement referred to as prehension. We developed an encoding model of hand kinematics to test whether single motor cortical (MI) neurons encode temporally extensive combinations of joint motions that characterize a prehensile movement. Two female rhesus macaque monkeys were trained to grasp 4 different objects presented by a robot while their arm was held in place by a thermoplastic brace. We used multi-electrode arrays to record MI neurons and an infrared camera motion tracking system to record the 3D positions of 14 markers placed on the monkeys’ wrist and digits. A generalized linear model framework was used to predict the firing rate of each neuron in a 4ms time interval, based on its own spiking history and the spatiotemporal kinematics of the joint angles of the hand. Our results show that the variability of the firing rate of MI neurons is better described by temporally extensive combinations of finger and wrist joint angle kinematics rather than any individual joint motion or any combination of static kinematic parameters at their optimal lag. Moreover, a higher percentage of neurons encoded joint angular velocities than joint angular positions. These results suggest that neurons encode the co-varying trajectories of the hand’s joints during a prehensile movement. PMID:21159978

  11. Botulinum Neurotoxins A and E Undergo Retrograde Axonal Transport in Primary Motor Neurons

    PubMed Central

    Manich, Maria; Bercsenyi, Kinga; Menendez, Guillermo; Rossetto, Ornella; Caleo, Matteo; Schiavo, Giampietro

    2012-01-01

    The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to the different fate of the parental neurotoxins once internalised in motor neurons. Tetanus toxin (TeNT) is known to undergo transcytosis into inhibitory interneurons and block the release of inhibitory neurotransmitters in the spinal cord, causing a spastic paralysis. In contrast, botulinum neurotoxins (BoNTs) block acetylcholine release at the neuromuscular junction, therefore inducing a flaccid paralysis. Whilst overt experimental evidence supports the sorting of TeNT to the axonal retrograde transport pathway, recent findings challenge the established view that BoNT trafficking is restricted to the neuromuscular junction by highlighting central effects caused by these neurotoxins. These results suggest a more complex scenario whereby BoNTs also engage long-range trafficking mechanisms. However, the intracellular pathways underlying this process remain unclear. We sought to fill this gap by using primary motor neurons either in mass culture or differentiated in microfluidic devices to directly monitor the endocytosis and axonal transport of full length BoNT/A and BoNT/E and their recombinant binding fragments. We show that BoNT/A and BoNT/E are internalised by spinal cord motor neurons and undergo fast axonal retrograde transport. BoNT/A and BoNT/E are internalised in non-acidic axonal carriers that partially overlap with those containing TeNT, following a process that is largely independent of stimulated synaptic vesicle endo-exocytosis. Following intramuscular injection in vivo, BoNT/A and TeNT displayed central effects with a similar time course. Central actions paralleled the peripheral spastic paralysis for TeNT, but lagged behind the onset of flaccid paralysis for BoNT/A. These results suggest that the fast axonal retrograde transport compartment is composed of multifunctional trafficking organelles orchestrating the simultaneous transfer of diverse cargoes

  12. Comparison of effects of transcranial magnetic stimulation on primary motor cortex and supplementary motor area in motor skill learning (randomized, cross over study).

    PubMed

    Kim, Yong Kyun; Shin, Sung Hun

    2014-01-01

    Motor skills require quick visuomotor reaction time, fast movement time, and accurate performance. Primary motor cortex (M1) and supplementary motor area (SMA) are closely related in learning motor skills. Also, it is well known that high frequency repeated transcranial magnetic stimulation (rTMS) on these sites has a facilitating effect. The aim of this study was to compare the effects of high frequency rTMS activation of these two brain sites on learning of motor skills. Twenty three normal volunteers participated. Subjects were randomly stimulated on either brain area, SMA or M1. The motor task required the learning of sequential finger movements, explicitly or implicitly. It consisted of pressing the keyboard sequentially with their right hand on seeing 7 digits on the monitor explicitly, and then tapping the 7 digits by memorization, implicitly. Subjects were instructed to hit the keyboard as fast and accurately as possible. Using Musical Instrument Digital Interface (MIDI), the keyboard pressing task was measured before and after high frequency rTMS for motor performance, which was measured by response time (RT), movement time, and accuracy (AC). A week later, the same task was repeated by cross-over study design. At this time, rTMS was applied on the other brain area. Two-way ANOVA was used to assess the carry over time effect and stimulation sites (M1 and SMA), as factors. Results indicated that no carry-over effect was observed. The AC and RT were not different between the two stimulating sites (M1 and SMA). But movement time was significantly decreased after rTMS on both SMA and M1. The amount of shortened movement time after rTMS on SMA was significantly increased as compared to the movement time after rTMS on M1 (p < 0.05), especially for implicit learning of motor tasks. The coefficient of variation was lower in implicit trial than in explicit trial. In conclusion, this finding indicated an important role of SMA compared to M1, in implicit motor

  13. Reduced inhibition within primary motor cortex in patients with poststroke focal motor seizures.

    PubMed

    Kessler, Kirn R; Schnitzler, Alfons; Classen, Joseph; Benecke, Reiner

    2002-10-08

    Following an ischemic brain lesion, the affected cortex undergoes structural and functional changes that may lead to increased cortical excitability or decreased inhibitory neuronal activity, resulting in the occurrence of poststroke epileptic seizures in 6 to 10% of patients with stroke. To assess motor cortical excitability, transcranial magnetic stimulation (TMS) was used to determine the silent period (SP) duration in 84 consecutive patients with ischemic stroke. In a subpopulation of six patients (38 to 72 years old) a significant decrease of the SP duration (mean 116 +/- 14 msec) was detected in either the arm or the leg on the affected side as compared to the corresponding unaffected limb (mean 231 +/- 32 msec). This electrophysiologic abnormality was clinically associated with focal motor seizures in five of the six patients, whereas none of the other 76 patients with normal or prolonged SP durations developed seizures or epilepsy. Silent period shortening in this group reflects decreased inhibitory activity that may partly be related to functional or structural impairment of GABAergic interneurons. TMS may be of value for determining patients with stroke at risk for developing poststroke seizures.

  14. Primary cell culture method for the honeybee Apis mellifera.

    PubMed

    Ju, Hyunhee; Ghil, Sungho

    2015-10-01

    Honeybees are among the most important pollinators in nature, and honeybee-associated products are useful in various areas, including the food industry. However, honeybees may be infected by various types of pathogens. The study of honeybee-associated diseases would greatly benefit from a successful cell culture system, but although some honeybee cell culture techniques have been introduced, these methods have not yet been fully established. Here, we describe a primary cell culture method for the honeybee, Apis mellifera. We isolated, sterilized, and seeded egg cells into non-coated cell culture dishes to generate cell aggregates. After approximately 10 d, aggregates were dissociated and seeded to cell culture dishes. Cell passages were continuously performed, with sub-culturing every 3-4 d. The cells expressed non-adherent phenotypes. Their growth increased with the passage number when they were cultured in growth medium based on L-15 insect medium but not Schneider's insect medium. Finally, polymerase chain reaction confirmed that the cells originated from A. mellifera. Our results suggest that the culturing methods described herein are appropriate for isolating primary cells from honeybee eggs. These methods could thus facilitate the study of honeybee-associated pathogenesis, development, and toxicology.

  15. Quantification of primary motor pathways using diffusion MRI tractography and its application to predict postoperative motor deficits in children with focal epilepsy.

    PubMed

    Jeong, Jeong-Won; Asano, Eishi; Juhász, Csaba; Chugani, Harry T

    2014-07-01

    As a new tool to quantify primary motor pathways and predict postoperative motor deficits in children with focal epilepsy, the present study utilized a maximum a posteriori probability (MAP) classification of diffusion weighted imaging (DWI) tractography combined with Kalman filter. DWI was performed in 31 children with intractable focal epilepsy who underwent epilepsy surgery. Three primary motor pathways associated with "finger," "leg," and "face" were classified using DWI-MAP classifier and compared with the results of invasive electrical stimulation mapping (ESM) via receiver operating characteristic (ROC) curve analysis. The Kalman filter analysis was performed to generate a model to determine the probability of postoperative motor deficits as a function of the proximity between the resection margin and the finger motor pathway. The ROC curve analysis showed that the DWI-MAP achieves high accuracy up to 89% (finger), 88% (leg), 89% (face), in detecting the three motor areas within 20 mm, compared with ESM. Moreover, postoperative reduction of the fiber count of finger pathway was associated with postoperative motor deficits involving the hand. The prediction model revealed an accuracy of 92% in avoiding postoperative deficits if the distance between the resection margin and the finger motor pathway seen on preoperative DWI tractography was 19.5 mm. This study provides evidence that the DWI-MAP combined with Kalman filter can effectively identify the locations of cortical motor areas even in patients whose motor areas are difficult to identify using ESM, and also can serve as a reliable predictor for motor deficits following epilepsy surgery.

  16. Factors associated with motor performance among overweight and nonoverweight Tyrolean primary school children.

    PubMed

    Ruedl, Gerhard; Greier, Klaus; Kirschner, Werner; Kopp, Martin

    2016-01-01

    The increasing prevalence of overweight and obesity among children is often associated with motor deficits. Motor performance among children partly depends on modifiable factors, for example, weight status, electronic media use, sports club participation, and on nonmodifiable factors, for example, sex, age, migration background, or socio-economic status. To evaluate factors associated with motor performance among overweight and nonoverweight Tyrolean primary school children. Height, weight, and sport motor performance of primary school children were measured using the German motor performance test DMT 6-18. In addition, children were asked about migration background, sports club participation, and electronic media use in their room. A total of 304 children (48.7% girls) with a mean age of 8.0 ± 1.2 years were tested. In total, 61 (20.1%) children were overweight or obese. Regarding motor performance, nonoverweight children showed significantly higher total z-scores (106.8 ± 5.7 vs. 102.4 ± 6.8). For the total cohort, results of the multiple linear regression analysis (R (2) = 0.20) revealed that factors male sex (β = 0.12), nonoverweight children (β = 0.28), higher school grade (β = 0.23), sports club participation (β = 0.18),and > 2 weekly lessons of physical education (β = 0.26) were associated with an increased motor performance. For nonoverweight children results of the multiple linear regression analysis (R (2) = 0.09) found that a higher school grade (β = 0.17), sports club participation (β = 0.16),and more than 2 weekly lessons of physical education (β = 0.22) were associated with an increased motor performance. For the overweight children, results of the multiple linear regression analysis (R (2) = 0 .43) showed that no migration background (β = 0.23), a higher school grade (β = 0.55), sports club participation (β = 0.33) and more than 2 weekly lessons of physical

  17. Epigenetic Modifications as Antidedifferentiation Strategy for Primary Hepatocytes in Culture.

    PubMed

    Bolleyn, Jennifer; Fraczek, Joanna; Rogiers, Vera; Vanhaecke, Tamara

    2015-01-01

    A well-known problem of cultured primary hepatocytes is their rapid dedifferentiation. During the last years, several strategies to counteract this phenomenon have been developed, of which changing the in vitro environment is the most popular one. However, mimicking the in vivo setting in vitro by adding soluble media additives or the restoration of both cell-cell and cell-extracellular matrix contacts is not sufficient and only delays the dedifferentiation process instead of counteracting it. In this chapter, new strategies to prevent the deterioration of the liver-specific phenotype of primary hepatocytes in culture by targeting the (epi)genetic mechanisms that drive hepatocellular gene expression are described.

  18. The effects of acute aerobic exercise on the primary motor cortex.

    PubMed

    Singh, Amaya M; Staines, W Richard

    2015-01-01

    The effect of aerobic exercise on primary motor cortical excitability is a relevant area of interest for both motor learning and motor rehabilitation. Transient excitability changes that may follow an exercise session are a necessary precursor to more lasting neuroplastic changes. While the number of studies is limited, research suggests that a session of aerobic exercise can create an ideal environment for the early induction of plasticity. Potential mechanisms include the upregulation of neurotransmitter activity, altered cerebral metabolism and cortisol levels, and increases in brain-derived neurotrophic factor. While there is considerable evidence that chronic physical activity positively impacts brain health and function, studies examining cortical excitability changes and motor performance after a single session of exercise are lacking. Further research is required to determine the clinical utility and feasibility of aerobic exercise.

  19. The primary motor area for voluntary diaphragmatic motion identified by high field fMRI.

    PubMed

    Nakayama, Takahiro; Fujii, Yukihiko; Suzuki, Kiyotaka; Kanazawa, Ichiro; Nakada, Tsutomu

    2004-06-01

    In order to identify the precise location of the primary motor area for the diaphragm with respect to the classical motor homunculus, functional magnetic resonance imaging (fMRI) experiments were performed utilizing independent component-cross correlation- sequential epoch (ICS) analysis on a high-field (3.0 Tesla) system. Activations which correlated with voluntary diaphragmatic motion mapped onto the area anterolateral to that for voluntary hand motion (internal control in ICS analysis). Multiple subject analysis yielded the primary motor cortex for the diaphragm to be (+/-48, -4, 47) in the Talairach and Tournoux coordinates. The results were highly consistent with the previously reported cortical area for the diaphragm determined by transcranial electrical/magnetic stimulation.

  20. 9 CFR 3.114 - Primary conveyances (motor vehicle, rail, air and marine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling... conveyances (motor vehicle, rail, air and marine). (a) The animal cargo space of primary conveyances used in... animal cargo space must be constructed and maintained in a manner that will prevent the ingress of engine...

  1. 9 CFR 3.138 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used in... comfort of the live animals contained therein at all times. (b) The animal cargo space shall be...

  2. 9 CFR 3.88 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling... conveyances (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used to... cargo space must have a supply of air that is sufficient for the normal breathing of all the animals...

  3. 9 CFR 3.138 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used in... comfort of the live animals contained therein at all times. (b) The animal cargo space shall be...

  4. 9 CFR 3.88 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling... conveyances (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used to... cargo space must have a supply of air that is sufficient for the normal breathing of all the animals...

  5. 9 CFR 3.114 - Primary conveyances (motor vehicle, rail, air and marine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling... conveyances (motor vehicle, rail, air and marine). (a) The animal cargo space of primary conveyances used in... animal cargo space must be constructed and maintained in a manner that will prevent the ingress of engine...

  6. 9 CFR 3.62 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... temperature in the animal cargo space is 75 °F (23.9 °C) or higher. The ambient temperature within the animal... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Primary conveyances (motor vehicle, rail, air, and marine). 3.62 Section 3.62 Animals and Animal Products ANIMAL AND PLANT...

  7. Effectiveness of Physical Education to Promote Motor Competence in Primary School Children

    ERIC Educational Resources Information Center

    Lopes, Vítor P.; Stodden, David F.; Rodrigues, Luis P.

    2017-01-01

    Background: Motor skill (MS) competence is an important contributing factor for healthy development. Purpose: The goal was to test the effectiveness of primary school physical education (PE) on MS and physical fitness (PF) development. Methods: Three classes (n = 60, aged 9.0 ± 0.9) were randomly assigned to three diverse conditions during a…

  8. 9 CFR 3.62 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., blowers, or air conditioners, shall be used in any cargo space containing live rabbits when the ambient..., rail, air, and marine). 3.62 Section 3.62 Animals and Animal Products ANIMAL AND PLANT HEALTH... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used in...

  9. 9 CFR 3.62 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., blowers, or air conditioners, shall be used in any cargo space containing live rabbits when the ambient..., rail, air, and marine). 3.62 Section 3.62 Animals and Animal Products ANIMAL AND PLANT HEALTH... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used in...

  10. 9 CFR 3.62 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., blowers, or air conditioners, shall be used in any cargo space containing live rabbits when the ambient..., rail, air, and marine). 3.62 Section 3.62 Animals and Animal Products ANIMAL AND PLANT HEALTH... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used in...

  11. 9 CFR 3.62 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., blowers, or air conditioners, shall be used in any cargo space containing live rabbits when the ambient..., rail, air, and marine). 3.62 Section 3.62 Animals and Animal Products ANIMAL AND PLANT HEALTH... (motor vehicle, rail, air, and marine). (a) The animal cargo space of primary conveyances used in...

  12. Organelle Transport in Cultured Drosophila Cells: S2 Cell Line and Primary Neurons.

    PubMed Central

    Gelfand, Vladimir I.

    2013-01-01

    Drosophila S2 cells plated on a coverslip in the presence of any actin-depolymerizing drug form long unbranched processes filled with uniformly polarized microtubules. Organelles move along these processes by microtubule motors. Easy maintenance, high sensitivity to RNAi-mediated protein knock-down and efficient procedure for creating stable cell lines make Drosophila S2 cells an ideal model system to study cargo transport by live imaging. The results obtained with S2 cells can be further applied to a more physiologically relevant system: axonal transport in primary neurons cultured from dissociated Drosophila embryos. Cultured neurons grow long neurites filled with bundled microtubules, very similar to S2 processes. Like in S2 cells, organelles in cultured neurons can be visualized by either organelle-specific fluorescent dyes or by using fluorescent organelle markers encoded by DNA injected into early embryos or expressed in transgenic flies. Therefore, organelle transport can be easily recorded in neurons cultured on glass coverslips using living imaging. Here we describe procedures for culturing and visualizing cargo transport in Drosophila S2 cells and primary neurons. We believe that these protocols make both systems accessible for labs studying cargo transport. PMID:24300413

  13. Organelle transport in cultured Drosophila cells: S2 cell line and primary neurons.

    PubMed

    Lu, Wen; Del Castillo, Urko; Gelfand, Vladimir I

    2013-11-20

    Drosophila S2 cells plated on a coverslip in the presence of any actin-depolymerizing drug form long unbranched processes filled with uniformly polarized microtubules. Organelles move along these processes by microtubule motors. Easy maintenance, high sensitivity to RNAi-mediated protein knock-down and efficient procedure for creating stable cell lines make Drosophila S2 cells an ideal model system to study cargo transport by live imaging. The results obtained with S2 cells can be further applied to a more physiologically relevant system: axonal transport in primary neurons cultured from dissociated Drosophila embryos. Cultured neurons grow long neurites filled with bundled microtubules, very similar to S2 processes. Like in S2 cells, organelles in cultured neurons can be visualized by either organelle-specific fluorescent dyes or by using fluorescent organelle markers encoded by DNA injected into early embryos or expressed in transgenic flies. Therefore, organelle transport can be easily recorded in neurons cultured on glass coverslips using living imaging. Here we describe procedures for culturing and visualizing cargo transport in Drosophila S2 cells and primary neurons. We believe that these protocols make both systems accessible for labs studying cargo transport.

  14. Coculture of Primary Motor Neurons and Schwann Cells as a Model for In Vitro Myelination.

    PubMed

    Hyung, Sujin; Yoon Lee, Bo; Park, Jong-Chul; Kim, Jinseok; Hur, Eun-Mi; Francis Suh, Jun-Kyo

    2015-10-12

    A culture system that can recapitulate myelination in vitro will not only help us better understand the mechanism of myelination and demyelination, but also find out possible therapeutic interventions for treating demyelinating diseases. Here, we introduce a simple and reproducible myelination culture system using mouse motor neurons (MNs) and Schwann cells (SCs). Dissociated motor neurons are plated on a feeder layer of SCs, which interact with and wrap around the axons of MNs as they differentiate in culture. In our MN-SC coculture system, MNs survived over 3 weeks and extended long axons. Both viability and axon growth of MNs in the coculture were markedly enhanced as compared to those of MN monoculture. Co-labeling of myelin basic proteins (MBPs) and neuronal microtubules revealed that SC formed myelin sheaths by wrapping around the axons of MNs. Furthermore, using the coculture system we found that treatment of an antioxidant substance coenzyme Q10 (Co-Q10) markedly facilitated myelination.

  15. Coculture of Primary Motor Neurons and Schwann Cells as a Model for In Vitro Myelination

    PubMed Central

    Hyung, Sujin; Yoon Lee, Bo; Park, Jong-Chul; Kim, Jinseok; Hur, Eun-Mi; Francis Suh, Jun-Kyo

    2015-01-01

    A culture system that can recapitulate myelination in vitro will not only help us better understand the mechanism of myelination and demyelination, but also find out possible therapeutic interventions for treating demyelinating diseases. Here, we introduce a simple and reproducible myelination culture system using mouse motor neurons (MNs) and Schwann cells (SCs). Dissociated motor neurons are plated on a feeder layer of SCs, which interact with and wrap around the axons of MNs as they differentiate in culture. In our MN-SC coculture system, MNs survived over 3 weeks and extended long axons. Both viability and axon growth of MNs in the coculture were markedly enhanced as compared to those of MN monoculture. Co-labeling of myelin basic proteins (MBPs) and neuronal microtubules revealed that SC formed myelin sheaths by wrapping around the axons of MNs. Furthermore, using the coculture system we found that treatment of an antioxidant substance coenzyme Q10 (Co-Q10) markedly facilitated myelination. PMID:26456300

  16. Modulation of excitability in human primary somatosensory and motor cortex by paired associative stimulation targeting the primary somatosensory cortex.

    PubMed

    Kriváneková, Lucia; Lu, Ming-Kuei; Bliem, Barbara; Ziemann, Ulf

    2011-10-01

    Input from primary somatosensory cortex (S1) to primary motor cortex (M1) is important for high-level motor performance, motor skill learning and motor recovery after brain lesion. This study tested the effects of manipulating S1 excitability with paired associative transcranial stimulation (S1-PAS) on M1 excitability. Given the important role of S1 in sensorimotor integration, we hypothesized that changes in S1 excitability would be directly paralleled by changes in M1 excitability. We applied two established protocols (S1-PAS(LTP) and S1-PAS(LTD) ) to the left S1 to induce long-term potentiation (LTP)-like or long-term depression (LTD)-like plasticity. S1 excitability was assessed by the early cortical components (N20-P25) of the median nerve somatosensory-evoked potential. M1 excitability was assessed by motor-evoked potential amplitude and short-interval intracortical inhibition. Effects of S1-PAS(LTP) were compared with those of a PAS(LTP) protocol targeting the left M1 (M1-PAS(LTP) ). S1-PAS(LTP) and S1-PAS(LTD) did not result in significant modifications of S1 or M1 excitability at the group level due to substantial interindividual variability. The individual S1-PAS-induced changes in S1 and M1 excitability showed no correlation. Furthermore, the individual changes in S1 and M1 excitability induced by S1-PAS(LTP) did not correlate with changes in M1 excitability induced by M1-PAS(LTP) . This demonstrates that the effects of S1-PAS in S1 are variable across individuals and, within a given individual, unrelated to those induced by S1-PAS or M1-PAS in M1. Potentially, this extends the opportunities of therapeutic PAS applications because M1-PAS 'non-responders' may well respond to S1-PAS.

  17. Where Cultural Games Count: The Voices of Primary Classroom Teachers

    ERIC Educational Resources Information Center

    Nabie, Michael Johnson

    2015-01-01

    This study explored Ghanaian primary school teachers' values and challenges of integrating cultural games in teaching mathematics. Using an In-depth conversational interview, ten (10) certificated teachers' voices on the values and challenges of integrating games were examined. Thematic data analysis was applied to the qualitative data from the…

  18. Creativity and Performativity Policies in Primary School Cultures

    ERIC Educational Resources Information Center

    Troman, Geoff; Jeffrey, Bob; Raggl, Andrea

    2007-01-01

    Cultures of performativity in English primary schools refer to systems and relationships of: target-setting; Ofsted inspections; school league tables constructed from pupil test scores; performance management; performance related pay; threshold assessment; and advanced skills teachers. Systems which demand that teachers "perform" and in…

  19. A gait paradigm reveals different patterns of abnormal cerebellar motor learning in primary focal dystonias.

    PubMed

    Hoffland, B S; Veugen, L C; Janssen, M M H P; Pasman, J W; Weerdesteyn, V; van de Warrenburg, B P

    2014-12-01

    Accumulating evidence points to a role of the cerebellum in the pathophysiology of primary dystonia. The aim of this study was to investigate whether the abnormalities of cerebellar motor learning in primary dystonia are solely detectable in more pure forms of cerebellum-dependent associative motor learning paradigms, or whether these are also present in other motor learning paradigms that rely heavily on the cerebellum but in addition require a more widespread sensorimotor network. Twenty-six patients with various forms of focal dystonia and 10 age-matched healthy controls participated in a motor learning paradigm on a split-belt treadmill. By using reflective markers, three-dimensional kinematics were recorded using a 6-camera motion analysis system. Adaptation walking parameters were analyzed offline, comparing the different dystonia groups and healthy controls. Patients with blepharospasm and writer's cramp were significantly impaired on various adaptation walking parameters. Whereas results of cervical dystonia patients did not differ from healthy controls in terms of adaptation walking parameters, differences in parameters of normal gait were found. We have here demonstrated abnormal sensorimotor adaptation with the split-belt paradigm in patients with blepharospasm and writer's cramp. This reinforces the current concept of cerebellar dysfunction in primary dystonia, and that this extends beyond more pure forms of cerebellum-dependent associative motor learning paradigms. However, the finding of normal adaptation in cervical dystonia patients indicates that the pattern of cerebellar dysfunction may be slightly different for the various forms of primary focal dystonia, suggesting that actual cerebellar pathology may not be a primary driving force in dystonia.

  20. Acetaminophen metabolism, cytotoxicity, and genotoxicity in rat primary hepatocyte cultures

    SciTech Connect

    Milam, K.M.; Byard, J.L.

    1985-06-30

    Acetaminophen (APAP) metabolism, cytotoxicity, and genotoxicity were measured in primary cultures of rat hepatocytes. Although 3 mM APAP caused a slight increase in cellular release of lactate dehydrogenase into the culture medium, cellular glutathione concentration (an index of APAP metabolism) was reduced by 50%. APAP at 7 mM was significantly more toxic to these hepatocytes and had a similar but more marked effect on glutathione concentrations. In spite of its cytotoxicity, neither dose of APAP stimulated DNA repair synthesis when monitored by the rate of incorporation of (/sup 3/H)thymidine into DNA following exposure to APAP. Thus, although APAP has been shown to be both hepato- and nephrotoxic in several in vivo and in vitro systems, the reactive toxic metabolite of APAP is not genotoxic in rat primary hepatocyte cultures.

  1. Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson's disease.

    PubMed

    Eggers, Carsten; Fink, Gereon R; Nowak, Dennis A

    2010-10-01

    The purpose of this study was to investigate whether a period of continuous theta burst stimulation (cTBS) induces cortical plasticity and thus improves bradykinesia of the upper limb in Parkinson's disease. In eight patients with Parkinson's disease (two females; mean age: 68.5 ± 5 years; disease duration: 4 ± 3 years) electrophysiological (motor evoked potentials, contralateral and ipsilateral silent period) and behavioural (Purdue pegboard test, UPDRS motor subscore) parameters were evaluated before (baseline condition) and after a 40-s period of (1) real or (2) sham continuous theta burst stimulation over the primary motor cortex contralateral to the more affected body side off dopaminergic drugs. Compared to baseline, cTBS did change neither measures of cortical excitability nor behavioural measures. cTBS over the primary motor cortex does not impact on cortical excitability or motor function of the upper limb in Parkinson's disease. We interpret these data to reflect impaired cortical plasticity in Parkinson's disease. This study is an important contribution to the knowledge about impaired plasticity in Parkinson's disease.

  2. [Characterization of epithelial primary culture from human conjunctiva].

    PubMed

    Rivas, L; Blázquez, A; Muñoz-Negrete, F J; López, S; Rebolleda, G; Domínguez, F; Pérez-Esteban, A

    2014-01-01

    To evaluate primary cultures from human conjunctiva supplemented with fetal bovine serum, autologous serum, and platelet-rich autologous serum, over human amniotic membrane and lens anterior capsules. One-hundred and forty-eight human conjunctiva explants were cultured in CnT50(®) supplemented with 1, 2.5, 5 and 10% fetal bovine serum, autologous serum and platelet-rich autologous serum. Conjunctival samples were incubated at 37°C, 5% CO2 and 95% HR, for 3 weeks. The typical phenotype corresponding to conjunctival epithelial cells was present in all primary cultures. Conjunctival cultures had MUC5AC-positive secretory cells, K19-positive conjunctival cells, and MUC4-positive non-secretory conjunctival cells, but were not corneal phenotype (cytokeratin K3-negative) and fibroblasts (CD90-negative). Conjunctiva epithelial progenitor cells were preserved in all cultures; thus, a cell culture in CnT50(®) supplemented with 1 to 5% autologous serum over human amniotic membrane can provide better information of epithelial cell differentiation for the conjunctival surface reconstruction. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  3. Efficacy of parent-delivered behavioral therapy for primary complex motor stereotypies.

    PubMed

    Specht, Matthew W; Mahone, E Mark; Kline, Tina; Waranch, Richard; Brabson, Laurel; Thompson, Carol B; Singer, Harvey S

    2017-02-01

    Primary complex motor stereotypies (CMS) are persistent, patterned, repetitive, rhythmic movements in young people with typical development. This study evaluated the efficacy of an instructional DVD as a home-based, parent-administered, behavioral therapy for primary CMS. Eighty-one children with primary CMS were enrolled. Primary outcome measures included the Stereotypy Severity Scale (SSS) - Motor and Impairment scores, and Stereotypy Linear Analog Scale (SLAS). Mean CMS onset was 13.4 months (SD 13.1). Eligibility required observed CMS. Psychiatric disorders were not exclusionary and a stable medication regimen was required. Intellectual disability, neurological disorder, autism spectrum disorder, and tics were exclusionary. Initial assessments were completed via REDCap before receipt of the DVD. Fifty-four of the 81 children (34 male, 20 female; mean age 8y 2mo, SD 1.42, range 7-14y) completed assessments at 1, 2, or 3 months after receiving the DVD. Reductions (baseline to last assessment) in SSS Motor, SSS Impairment, and SLAS scores (all p<0.001) represented change ratios of -15%, -24%, and a -20% respectively. Greatest relative treatment benefit was observed by younger children (ages 7-8y), and by 1 month after receipt of DVD, while a parent global assessment scale showed progressive improvement throughout the study. An instructional DVD for parent-delivered behavioral therapy was a safe, effective intervention for primary CMS. © 2016 Mac Keith Press.

  4. Culture-bound syndromes in Hispanic primary care patients.

    PubMed

    Bayles, Bryan P; Katerndahl, David A

    2009-01-01

    We sought to document Hispanic primary care patients' knowledge and experience of five culture-bound syndromes (CBS), as well as the basic socio-cultural correlates of these disorders. A convenience sample of 100 adult Hispanic patients presenting in an urban South Texas primary care clinic was recruited to complete a brief cross-sectional survey, presented in an oral format. Interviews sought information concerning five culture-bound syndromes--susto, empacho, nervios, mal de ojo, and ataques de nervios. Additional demographic, socio-economic, and acculturation data was collected. Descriptive and bivariate statistics (chi square, Fisher's) were used to assess relationships among variables and experience with each CBS. A multivariate logistic analysis was conducted to determine the possible contributions of age, gender, acculturation, and education to the personal experience of a culture-bound syndrome. Results indicate that 77% of respondents had knowledge of all five syndromes, with 42% reporting having personally experienced at least one CBS. Nervios was the most commonly suffered disorder, being reported by 30 respondents. This was followed, in declining order ofprevalence, by susto, mal de ojo, empacho, and ataques de nervios. Multivariate logistic regression analysis found that higher education beyond high school was associated with a slightly decreased likelihood of reporting having suffered from any culture-bound syndrome. While co-occurrence among these disorders occurred, the patterns of predictors suggest that the co-occurrence is not a reflection of mislabeling of one common syndrome. Knowledge of and experience with culture-bound syndromes is common among Hispanic primary care patients in South Texas. Healthcare providers ought to consider discussing these illnesses in a non-judgmental manner with patients who present with symptoms that are consistent with these syndromes. Future studies, with larger sample sizes, are warranted to elucidate the nature

  5. Micropatterned bioimplant with guided neuronal cells to promote tissue reconstruction and improve functional recovery after primary motor cortex insult.

    PubMed

    Vaysse, L; Beduer, A; Sol, J C; Vieu, C; Loubinoux, I

    2015-07-01

    With the ever increasing incidence of brain injury, developing new tissue engineering strategies to promote neural tissue regeneration is an enormous challenge. The goal of this study was to design and evaluate an implantable scaffold capable of directing neurite and axonal growth for neuronal brain tissue regeneration. We have previously shown in cell culture conditions that engineered micropatterned PDMS surface with straight microchannels allow directed neurite growth without perturbing cell differentiation and neurite outgrowth. In this study, the micropatterned PDMS device pre-seeded with hNT2 neuronal cells were implanted in rat model of primary motor cortex lesion which induced a strong motor deficit. Functional recovery was assessed by the forelimb grip strength test during 3 months post implantation. Results show a more rapid and efficient motor recovery with the hNT2 neuroimplants associated with an increase of neuronal tissue reconstruction and cell survival. This improvement is also hastened when compared to a direct cell graft of ten times more cells. Histological analyses showed that the implant remained structurally intact and we did not see any evidence of inflammatory reaction. In conclusion, PDMS bioimplants with guided neuronal cells seem to be a promising approach for supporting neural tissue reconstruction after central brain injury.

  6. Primary complex motor stereotypies in older children and adolescents: clinical features and longitudinal follow-up.

    PubMed

    Oakley, Christopher; Mahone, E Mark; Morris-Berry, Christina; Kline, Tina; Singer, Harvey S

    2015-04-01

    Complex motor stereotypies are rhythmic, repetitive, fixed, and purposeless movements that stop with distraction. Once believed to occur only in children with autism spectrum or other developmental disorders, their presence in otherwise typically developing children (primary) has been well-established. In primary complex motor stereotypies, little information is available about the long-term outcome of these movements or existing comorbidities. Forty-nine healthy participants (31 boys), ages 9 to 20 years with primary complex motor stereotypies who were previously diagnosed at a pediatric movements disorder clinic, were identified from medical records. Parents or the young adult (if older than age 18), completed a telephone interview evaluating family history, outcome, and comorbidities including attention-deficit hyperactivity disorder, obsessive compulsive disorder, anxiety, and tics/Tourette syndrome. Standardized questionnaires assessing attention-deficit hyperactivity, obsessive compulsive disorder, and anxiety were used to validate parent report of comorbidities. Stereotypy onset occurred before age 3 years in 98%. In all but one individual, stereotypies persisted at the time of phone follow-up (follow-up range: 6.8-20.3 years). Positive family history of complex motor stereotypies was identified in 39%. Most participants (92%) had concern for at least one comorbid disorder, including parent-/patient-reported clinically elevated levels of anxiety (73%), attention-deficit hyperactivity (63%), obsessive compulsive disorder (35%), and tics/Tourette syndrome (22%). Primary motor stereotypies typically begin in early childhood and, although reduced in frequency and duration, persist at least through the teenage years. Repetitive movements are associated with a variety of comorbidities that often have a greater functional impact than the stereotypic behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture

    PubMed Central

    Li, Xingnan; Nadauld, Lincoln; Ootani, Akifumi; Corney, David C.; Pai, Reetesh K.; Gevaert, Olivier; Cantrell, Michael A.; Rack, Paul G.; Neal, James T.; Chan, Carol W-M.; Yeung, Trevor; Gong, Xue; Yuan, Jenny; Wilhelmy, Julie; Robine, Sylvie; Attardi, Laura D.; Plevritis, Sylvia K.; Hung, Kenneth E.; Chen, Chang-Zheng; Ji, Hanlee P.; Kuo, Calvin J.

    2014-01-01

    The application of primary organoid cultures containing epithelial and mesenchymal elements to cancer modeling holds promise for combining the accurate multilineage differentiation and physiology of in vivo systems with the facile in vitro manipulation of transformed cell lines. Here, a single air-liquid interface culture method was used without modification to engineer oncogenic mutations into primary epithelial/mesenchymal organoids from mouse colon, stomach and pancreas. Pancreatic and gastric organoids exhibited dysplasia upon KrasG12D expression and/or p53 loss, and readily generated adenocarcinoma upon in vivo transplantation. In contrast, primary colon organoids required combinatorial Apc, p53, KrasG12D and Smad4 mutations for progressive transformation to invasive adenocarcinoma-like histology in vitro and tumorigenicity in vivo, recapitulating multi-hit models of colorectal cancer (CRC), and versus more promiscuous transformation of small intestinal organoids. Colon organoid culture functionally validated the microRNA miR-483 as a dominant driver oncogene at the Insulin-like growth factor-2 (IGF2) 11p15.5 CRC amplicon, inducing dysplasia in vitro and tumorigenicity in vivo. These studies demonstrate the general utility of a highly tractable primary organoid system for cancer modeling and driver oncogene validation in diverse gastrointestinal tissues. PMID:24859528

  8. Cultural significance of primary teeth for caregivers in Northeast Brazil.

    PubMed

    Nations, Marilyn K; Calvasina, Paola Gondim; Martin, Michele N; Dias, Hilma Fontenele

    2008-04-01

    This anthropological study critically evaluates Brazilian caregivers' symbolic production and significance of their malnourished offspring's primary teeth, as well as their own, and describes popular dental practices. From January to June 2004, ethnographic interviews of 27 poor, low-literacy mothers were conducted at a public Malnutrition Treatment Center in Fortaleza, Ceará State. Participant observation of clinical pathways and home environments supplemented the data. Content analysis was performed. Results confirm that primary teeth are imbued with cultural significance in Northeast Brazil. Mothers examine mouths, perceive signs of decay, associate primary with permanent tooth healthiness, identify ethnodental illnesses, seek assistance, and perform rituals with exfoliated teeth. The mother's motivation to care for primary teeth is sparked by her memories of past toothache and attempts to avoid stigma and discrimination. Social determinants, not mothers' beliefs or behaviors, are the most critical obstacles to effective dental care. Legitimizing lay knowledge and empowering caregivers and children can improve oral health in Northeast Brazil.

  9. Establishment of Asian citrus psyllid (Diaphorina citri) primary cultures.

    PubMed

    Marutani-Hert, Mizuri; Hunter, Wayne B; Hall, David G

    2009-01-01

    The Asian citrus psyllid (AsCP), Diaphorina citri Kuwayama (Hemiptera: Psyllidae), is a highly competent vector of the phloem-inhabiting bacterium Candidatus Liberibacter asiaticus associated with the citrus disease huanglongbing (HLB). Commonly referred to as citrus greening disease in the USA, HLB causes reduced fruit yields, quality, and ultimately tree death and is considered the most serious citrus disease. HLB has become a major limiting factor to the production of citrus worldwide. Studies of HLB have been impeded by the fact that C. Liberibacter has not yet been cultured on artificial nutrient media. After being acquired by a psyllid, C. Liberibacter asiaticus is reported to replicate within the psyllid and is retained by the psyllid throughout its life span. We therefore hypothesized that C. Liberibacter asiaticus could be cultured in vitro using psyllid cell cultures as the medium and investigated the establishment of a pure culture for AsCP cells. Several commercially available insect cell culture media along with some media we developed were screened for viability to culture cells from AsCP embryos. Cells from psyllid tissues adhered to the plate and migration was observed within 24 h. Cells were maintained at 20 degrees C. We successfully established primary psyllid cell cultures, referred to as DcHH-1, for D. citri Hert-Hunter-1, with a new media, Hert-Hunter-70.

  10. Liposomal clodronate selectively eliminates microglia from primary astrocyte cultures

    PubMed Central

    2012-01-01

    Background There is increasing interest in astrocyte biology because astrocytes have been demonstrated to play prominent roles in physiological and pathological conditions of the central nervous system, including neuroinflammation. To understand astrocyte biology, primary astrocyte cultures are most commonly used because of the direct accessibility of astrocytes in this system. However, this advantage can be hindered by microglial contamination. Although several authors have warned regarding microglial contamination in this system, complete microglial elimination has never been achieved. Methods The number and proliferative potential of contaminating microglia in primary astrocyte cultures were quantitatively assessed by immunocytologic and flow cytometric analyses. To examine the utility of clodronate for microglial elimination, primary astrocyte cultures or MG-5 cells were exposed to liposomal or free clodronate, and then immunocytologic, flow cytometric, and gene expression analyses were performed. The gene expression profiles of microglia-eliminated and microglia-contaminated cultures were compared after interleukin-6 (IL-6) stimulation. Results The percentage of contaminating microglia exceeded 15% and continued to increase because of their high proliferative activity in conventional primary astrocyte cultures. These contaminating microglia were selectively eliminated low concentration of liposomal clodronate. Although primary microglia and MG-5 cells were killed by both liposomal and free clodronate, free clodronate significantly affected the viability of astrocytes. In contrast, liposomal clodronate selectively eliminated microglia without affecting the viability, proliferation or activation of astrocytes. The efficacy of liposomal clodronate was much higher than that of previously reported methods used for decreasing microglial contamination. Furthermore, we observed rapid tumor necrosis factor-α and IL-1b gene induction in conventional primary astrocyte

  11. A Causal Role for Primary Motor Cortex in Perception of Observed Actions

    PubMed Central

    Palmer, Clare E.; Bunday, Karen L.; Davare, Marco; Kilner, James M.

    2017-01-01

    It has been proposed that motor system activity during action observation may be modulated by the kinematics of observed actions. One purpose of this activity during action observation may be to predict the visual consequence of another person’s action based on their movement kinematics. Here, we tested the hypothesis that the primary motor cortex (M1) may have a causal role in inferring information that is present in the kinematics of observed actions. Healthy participants completed an action perception task before and after applying continuous theta burst stimulation (cTBS) over left M1. A neurophysiological marker was used to quantify the extent of M1 disruption following cTBS and stratify our sample a priori to provide an internal control. We found that a disruption to M1 caused a reduction in an individual’s sensitivity to interpret the kinematics of observed actions; the magnitude of suppression of motor excitability predicted this change in sensitivity. PMID:27458752

  12. [Participation of the primary motor cortex in programming of muscle activity during catching of falling object].

    PubMed

    Kazennikov, O V; Lipshits, M I

    2011-01-01

    Object fell into the cup that sitting subject held between thumb and index fingers. Transcranial magnetic stimulation (TMS) of the primary motor cortex was performed early before and during anticipatory grip force increasing. Comparison of current EMG activity of adductor pollicis brevis and first dorsal interosseous muscles and responses of these muscles on TMS showed that responses were increased before the raising of muscle activity. From the other side only slight augmentation of responses was observed during subsequent strong muscle activation. It is assumed that the increasing of the TMS responses that occurred before the initiation of muscle activity reflects the enhancement ofthe motor cortex excitability associated to specific processes related to the motor cortex participation in programming of the muscles activities.

  13. Negative blood oxygenation level dependent homunculus and somatotopic information in primary motor cortex and supplementary motor area

    PubMed Central

    Zeharia, Noa; Hertz, Uri; Flash, Tamar; Amedi, Amir

    2012-01-01

    A crucial attribute in movement encoding is an adequate balance between suppression of unwanted muscles and activation of required ones. We studied movement encoding across the primary motor cortex (M1) and supplementary motor area (SMA) by inspecting the positive and negative blood oxygenation level-dependent (BOLD) signals in these regions. Using periodic and event-related experiments incorporating the bilateral/axial movements of 20 body parts, we report detailed mototopic imaging maps in M1 and SMA. These maps were obtained using phase-locked analysis. In addition to the positive BOLD, significant negative BOLD was detected in M1 but not in the SMA. The negative BOLD spatial pattern was neither located at the ipsilateral somatotopic location nor randomly distributed. Rather, it was organized somatotopically across the entire homunculus and inversely to the positive BOLD, creating a negative BOLD homunculus. The neuronal source of negative BOLD is unclear. M1 provides a unique system to test whether the origin of negative BOLD is neuronal, because different arteries supply blood to different regions in the homunculus, ruling out blood-stealing explanations. Finally, multivoxel pattern analysis showed that positive BOLD in M1 and SMA and negative BOLD in M1 contain somatotopic information, enabling prediction of the moving body part from inside and outside its somatotopic location. We suggest that the neuronal processes underlying negative BOLD participate in somatotopic encoding in M1 but not in the SMA. This dissociation may emerge because of differences in the activity of these motor areas associated with movement suppression. PMID:23086164

  14. Negative blood oxygenation level dependent homunculus and somatotopic information in primary motor cortex and supplementary motor area.

    PubMed

    Zeharia, Noa; Hertz, Uri; Flash, Tamar; Amedi, Amir

    2012-11-06

    A crucial attribute in movement encoding is an adequate balance between suppression of unwanted muscles and activation of required ones. We studied movement encoding across the primary motor cortex (M1) and supplementary motor area (SMA) by inspecting the positive and negative blood oxygenation level-dependent (BOLD) signals in these regions. Using periodic and event-related experiments incorporating the bilateral/axial movements of 20 body parts, we report detailed mototopic imaging maps in M1 and SMA. These maps were obtained using phase-locked analysis. In addition to the positive BOLD, significant negative BOLD was detected in M1 but not in the SMA. The negative BOLD spatial pattern was neither located at the ipsilateral somatotopic location nor randomly distributed. Rather, it was organized somatotopically across the entire homunculus and inversely to the positive BOLD, creating a negative BOLD homunculus. The neuronal source of negative BOLD is unclear. M1 provides a unique system to test whether the origin of negative BOLD is neuronal, because different arteries supply blood to different regions in the homunculus, ruling out blood-stealing explanations. Finally, multivoxel pattern analysis showed that positive BOLD in M1 and SMA and negative BOLD in M1 contain somatotopic information, enabling prediction of the moving body part from inside and outside its somatotopic location. We suggest that the neuronal processes underlying negative BOLD participate in somatotopic encoding in M1 but not in the SMA. This dissociation may emerge because of differences in the activity of these motor areas associated with movement suppression.

  15. Speed of processing in the primary motor cortex: a continuous theta burst stimulation study.

    PubMed

    Lakhani, Bimal; Bolton, David A E; Miyasike-Dasilva, Veronica; Vette, Albert H; McIlroy, William E

    2014-03-15

    'Temporally urgent' reactions are extremely rapid, spatially precise movements that are evoked following discrete stimuli. The involvement of primary motor cortex (M1) and its relationship to stimulus intensity in such reactions is not well understood. Continuous theta burst stimulation (cTBS) suppresses focal regions of the cortex and can assess the involvement of motor cortex in speed of processing. The primary objective of this study was to explore the involvement of M1 in speed of processing with respect to stimulus intensity. Thirteen healthy young adults participated in this experiment. Behavioral testing consisted of a simple button press using the index finger following median nerve stimulation of the opposite limb, at either high or low stimulus intensity. Reaction time was measured by the onset of electromyographic activity from the first dorsal interosseous (FDI) muscle of each limb. Participants completed a 30 min bout of behavioral testing prior to, and 15 min following, the delivery of cTBS to the motor cortical representation of the right FDI. The effect of cTBS on motor cortex was measured by recording the average of 30 motor evoked potentials (MEPs) just prior to, and 5 min following, cTBS. Paired t-tests revealed that, of thirteen participants, five demonstrated a significant attenuation, three demonstrated a significant facilitation and five demonstrated no significant change in MEP amplitude following cTBS. Of the group that demonstrated attenuated MEPs, there was a biologically significant interaction between stimulus intensity and effect of cTBS on reaction time and amplitude of muscle activation. This study demonstrates the variability of potential outcomes associated with the use of cTBS and further study on the mechanisms that underscore the methodology is required. Importantly, changes in motor cortical excitability may be an important determinant of speed of processing following high intensity stimulation.

  16. The role of the premotor cortex and the primary motor cortex in action verb comprehension: evidence from Granger causality analysis.

    PubMed

    Yang, Jie; Shu, Hua

    2012-08-01

    Although numerous studies find the premotor cortex and the primary motor cortex are involved in action language comprehension, so far the nature of these motor effects is still in controversy. Some researchers suggest that the motor effects reflect that the premotor cortex and the primary motor cortex make functional contributions to the semantic access of action verbs, while other authors argue that the motor effects are caused by comprehension. In the current study, we used Granger causality analysis to investigate the roles of the premotor cortex and the primary motor cortex in processing of manual-action verbs. Regions of interest were selected in the primary motor cortex (M1) and the premotor cortex based on a hand motion task, and in the left posterior middle temporal gyrus (lexical semantic area) based on the reading task effect. We found that (1) the left posterior middle temporal gyrus had a causal influence on the left M1; and (2) the left posterior middle temporal gyrus and the left premotor cortex had bidirectional causal relations. These results suggest that the premotor cortex and the primary motor cortex play different roles in manual verb comprehension. The premotor cortex may be involved in motor simulation that contributes to action language processing, while the primary motor cortex may be engaged in a processing stage influenced by the meaning access of manual-action verbs. Further investigation combining effective connectivity analysis and technique with high temporal resolution is necessary for better clarification of the roles of the premotor cortex and the primary motor cortex in action language comprehension.

  17. Facilitating skilled right hand motor function in older subjects by anodal polarization over the left primary motor cortex.

    PubMed

    Hummel, Friedhelm C; Heise, Kirstin; Celnik, Pablo; Floel, Agnes; Gerloff, Christian; Cohen, Leonardo G

    2010-12-01

    Healthy ageing is accompanied by limitations in performance of activities of daily living and personal independence. Recent reports demonstrated improvements in motor function induced by noninvasive anodal direct current stimulation (tDCS) of the primary motor cortex (M1) in young healthy adults. Here we tested the hypothesis that a single session of anodal tDCS over left M1 could facilitate performance of right upper extremity tasks required for activities of daily living (Jebsen-Taylor hand function test, JTT) in older subjects relative to Sham in a double-blind cross-over study design. We found (a) significant improvement in JTT function with tDCS relative to Sham that outlasted the stimulation period by at least 30 min, (b) that the older the subjects the more prominent this improvement appeared and (c) that consistent with previous results in younger subjects, these effects were not accompanied by any overt undesired side effect. We conclude that anodal tDCS applied over M1 can facilitate performance of skilled hand functions required for activities of daily living in older subjects.

  18. The effector independent nature of motor imagery: Evidence from rTMS induced inhibition to the primary motor cortices.

    PubMed

    Kraeutner, Sarah N; Ingram, Tony G J; Boe, Shaun G

    2017-03-01

    Motor imagery (MI), the mental rehearsal of movement, facilitates learning by driving brain activation similar to that of physical practice (PP). However, a growing body of evidence suggests that learning via MI relies more on effector independent as opposed to effector dependent encoding. One approach to probing the nature of MI based learning is to study the primary motor cortex (MC), a brain region known to be critical to effector dependent encoding, but whose involvement in MI is debatable. The current study sought to inform on the nature of MI-based learning by examining the extent to which participants could learn via MI following inhibition of the MC using repetitive transcranial magnetic stimulation (TMS). Forty-seven participants completed an MI-based implicit sequence learning paradigm after receiving inhibitory TMS to the contralateral or ipsilateral MC (TMS groups), or with the coil angled away from the scalp (Sham). The extent to which participants learned was assessed via reaction time differences (dRT) and effect sizes between repeated and random sequences. Similar dRT values and moderate effect sizes were observed across all groups, providing evidence that inhibition of the MC did not disrupt MI-based learning. As the MC is critical to effector dependent encoding, the current findings suggest that MI-based learning does not rely on effector dependent encoding and unlike PP, is more effector independent in nature. Ultimately, these results inform on the nature of MI-based learning.

  19. Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy.

    PubMed

    Batista E Sá, Vagner Wilian; Gomes, Maria Katia; Rangel, Maria Luíza Sales; Sanchez, Tiago Arruda; Moreira, Filipe Azaline; Hoefle, Sebastian; Souto, Inaiacy Bittencourt; Cunha, Antônio José Ledo Alves da; Fontana, Ana Paula; Vargas, Claudia Domingues

    2015-01-01

    Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS). In a cross-sectional study design, we mapped bilaterally in the primary motor cortex (M1) the representations of the hand flexor digitorum superficialis (FDS), as well as of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent clinical assessment, handgrip dynamometry and motor and sensory nerve conduction exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were performed with an alpha-value of p<0.05. Dynamometry performance of the patients' most affected hand (MAH), was worse than that of the less affected hand (LAH) and of healthy controls participants (p = 0.031), confirming handgrip impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres in patients as compared to controls, and lower in the hemisphere contralateral to the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP) amplitudes collected in the FDS of the MAH were higher in comparison to those of controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes in the hemisphere contralateral to MAH as compared to those of the LAH and the control group. Taken together, these results are suggestive of a more robust representation of an extrinsic hand flexor and impaired intrinsic hand muscle function in the hemisphere contralateral to the MAH due to leprosy. Decreased sensory-motor function induced by leprosy

  20. Functional connectivity of primary motor cortex is dependent on genetic burden in prodromal Huntington disease.

    PubMed

    Koenig, Katherine A; Lowe, Mark J; Harrington, Deborah L; Lin, Jian; Durgerian, Sally; Mourany, Lyla; Paulsen, Jane S; Rao, Stephen M

    2014-09-01

    Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive-motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis.

  1. Functional Connectivity of Primary Motor Cortex Is Dependent on Genetic Burden in Prodromal Huntington Disease

    PubMed Central

    Koenig, Katherine A.; Lowe, Mark J.; Harrington, Deborah L.; Lin, Jian; Durgerian, Sally; Mourany, Lyla; Paulsen, Jane S.

    2014-01-01

    Abstract Subtle changes in motor function have been observed in individuals with prodromal Huntington disease (prHD), but the underlying neural mechanisms are not well understood nor is the cumulative effect of the disease (disease burden) on functional connectivity. The present study examined the resting-state functional magnetic resonance imaging (rs-fMRI) connectivity of the primary motor cortex (M1) in 16 gene-negative (NEG) controls and 48 gene-positive prHD participants with various levels of disease burden. The results showed that the strength of the left M1 connectivity with the ipsilateral M1 and somatosensory areas decreased as disease burden increased and correlated with motor symptoms. Weakened M1 connectivity within the motor areas was also associated with abnormalities in long-range connections that evolved with disease burden. In this study, M1 connectivity was decreased with visual centers (bilateral cuneus), but increased with a hub of the default mode network (DMN; posterior cingulate cortex). Changes in connectivity measures were associated with worse performance on measures of cognitive–motor functioning. Short- and long-range functional connectivity disturbances were also associated with volume loss in the basal ganglia, suggesting that weakened M1 connectivity is partly a manifestation of striatal atrophy. Altogether, the results indicate that the prodromal phase of HD is associated with abnormal interhemispheric interactions among motor areas and disturbances in the connectivity of M1 with visual centers and the DMN. These changes may, respectively, contribute to increased motor symptoms, visuomotor integration problems, and deficits in the executive control of movement as individuals approach a manifest diagnosis. PMID:25072408

  2. Transcranial direct current stimulation of the primary motor cortex improves word-retrieval in older adults

    PubMed Central

    Meinzer, Marcus; Lindenberg, Robert; Sieg, Mira M.; Nachtigall, Laura; Ulm, Lena; Flöel, Agnes

    2014-01-01

    Language facilitation by transcranial direct current stimulation (tDCS) in healthy individuals has generated hope that tDCS may also allow improving language impairment after stroke (aphasia). However, current stimulation protocols have yielded variable results and may require identification of residual language cortex using functional magnetic resonance imaging (fMRI), which complicates incorporation into clinical practice. Based on previous behavioral studies that demonstrated improved language processing by motor system pre-activation, the present study assessed whether tDCS administered to the primary motor cortex (M1) can enhance language functions. This proof-of-concept study employed a sham-tDCS controlled, cross-over, within-subject design and assessed the impact of unilateral excitatory (anodal) and bihemispheric (dual) tDCS in 18 healthy older adults during semantic word-retrieval and motor speech tasks. Simultaneous fMRI scrutinized the neural mechanisms underlying tDCS effects. Both active tDCS conditions significantly improved word-retrieval compared to sham-tDCS. The direct comparison of activity elicited by word-retrieval vs. motor-speech trials revealed bilateral frontal activity increases during both anodal- and dual-tDCS compared to sham-tDCS. This effect was driven by more pronounced deactivation of frontal regions during the motor-speech task, while activity during word-retrieval trials was unaffected by the stimulation. No effects were found in M1 and secondary motor regions. Our results show that tDCS administered to M1 can improve word-retrieval in healthy individuals, thereby providing a rationale to explore whether M1-tDCS may offer a novel approach to improve language functions in aphasia. Functional magnetic resonance imaging revealed neural facilitation specifically during motor speech trials, which may have reduced switching costs between the overlapping neural systems for lexical retrieval and speech processing, thereby resulting in

  3. Disruption of functional organization within the primary motor cortex in children with autism.

    PubMed

    Nebel, Mary Beth; Joel, Suresh E; Muschelli, John; Barber, Anita D; Caffo, Brian S; Pekar, James J; Mostofsky, Stewart H

    2014-02-01

    Accumulating evidence suggests that motor impairments are prevalent in autism spectrum disorder (ASD), relate to the social and communicative deficits at the core of the diagnosis and may reflect abnormal connectivity within brain networks underlying motor control and learning. Parcellation of resting-state functional connectivity data using spectral clustering approaches has been shown to be an effective means of visualizing functional organization within the brain but has most commonly been applied to explorations of normal brain function. This article presents a parcellation of a key area of the motor network, the primary motor cortex (M1), a key area of the motor control network, in adults, typically developing (TD) children and children with ASD and introduces methods for selecting the number of parcels, matching parcels across groups and testing group differences. The parcellation is based solely on patterns of connectivity between individual M1 voxels and all voxels outside of M1, and within all groups, a gross dorsomedial to ventrolateral organization emerged within M1 which was left-right symmetric. Although this gross organizational scheme was present in both groups of children, statistically significant group differences in the size and segregation of M1 parcels within regions of the motor homunculus corresponding to the upper and lower limbs were observed. Qualitative comparison of the M1 parcellation for children with ASD with that of younger and older TD children suggests that these organizational differences, with a lack of differentiation between lower limb/trunk regions and upper limb/hand regions, may be due, at least in part, to a delay in functional specialization within the motor cortex.

  4. Primary Motor Cortex Representation of Handgrip Muscles in Patients with Leprosy

    PubMed Central

    Rangel, Maria Luíza Sales; Sanchez, Tiago Arruda; Moreira, Filipe Azaline; Hoefle, Sebastian; Souto, Inaiacy Bittencourt; da Cunha, Antônio José Ledo Alves

    2015-01-01

    Background Leprosy is an endemic infectious disease caused by Mycobacterium leprae that predominantly attacks the skin and peripheral nerves, leading to progressive impairment of motor, sensory and autonomic function. Little is known about how this peripheral neuropathy affects corticospinal excitability of handgrip muscles. Our purpose was to explore the motor cortex organization after progressive peripheral nerve injury and upper-limb dysfunction induced by leprosy using noninvasive transcranial magnetic stimulation (TMS). Methods In a cross-sectional study design, we mapped bilaterally in the primary motor cortex (M1) the representations of the hand flexor digitorum superficialis (FDS), as well as of the intrinsic hand muscles abductor pollicis brevis (APB), first dorsal interosseous (FDI) and abductor digiti minimi (ADM). All participants underwent clinical assessment, handgrip dynamometry and motor and sensory nerve conduction exams 30 days before mapping. Wilcoxon signed rank and Mann-Whitney tests were performed with an alpha-value of p<0.05. Findings Dynamometry performance of the patients’ most affected hand (MAH), was worse than that of the less affected hand (LAH) and of healthy controls participants (p = 0.031), confirming handgrip impairment. Motor threshold (MT) of the FDS muscle was higher in both hemispheres in patients as compared to controls, and lower in the hemisphere contralateral to the MAH when compared to that of the LAH. Moreover, motor evoked potential (MEP) amplitudes collected in the FDS of the MAH were higher in comparison to those of controls. Strikingly, MEPs in the intrinsic hand muscle FDI had lower amplitudes in the hemisphere contralateral to MAH as compared to those of the LAH and the control group. Taken together, these results are suggestive of a more robust representation of an extrinsic hand flexor and impaired intrinsic hand muscle function in the hemisphere contralateral to the MAH due to leprosy. Conclusion Decreased

  5. Sensorimotor memory for fingertip forces during object lifting: the role of the primary motor cortex.

    PubMed

    Berner, Julia; Schönfeldt-Lecuona, Carlos; Nowak, Dennis A

    2007-04-09

    When an object is repetitively lifted, the scaling of grip force is influenced by the mechanical properties of the preceding lift, suggesting the formation of a sensorimotor memory. Similar effects on force scaling are observed when the subsequent lift is performed with the hand opposite to the preceding lift. We used neuronavigated rTMS over the hand area of the dominant primary motor cortex to investigate its role in setting up sensorimotor memory. After ten lifts of a novel object with the dominant hand either rTMS or a period of motor rest commenced, until another set of lifts was performed with either the same or opposite hand. Compared to motor rest, rTMS caused underestimation of the object's weight when given 10 or 30s after the previous set of lifts, but overestimation of the object's weight when applied 60 or 120 s after the previous set of lifts, regardless of the hand performing the lift. Our interpretation of the data is that (a) the primary motor cortex is essential for setting up sensorimotor memory related to the mechanical object properties during manipulation and (b) rTMS can induce bidirectional changes of grip efficiency within the dynamics of sensorimotor integration.

  6. The primary motor and premotor areas of the human cerebral cortex.

    PubMed

    Chouinard, Philippe A; Paus, Tomás

    2006-04-01

    Brodmann's cytoarchitectonic map of the human cortex designates area 4 as cortex in the anterior bank of the precentral sulcus and area 6 as cortex encompassing the precentral gyrus and the posterior portion of the superior frontal gyrus on both the lateral and medial surfaces of the brain. More than 70 years ago, Fulton proposed a functional distinction between these two areas, coining the terms primary motor area for cortex in Brodmann area 4 and premotor area for cortex in Brodmann area 6. The parcellation of the cortical motor system has subsequently become more complex. Several nonprimary motor areas have been identified in the brain of the macaque monkey, and associations between anatomy and function in the human brain are being tested continuously using brain mapping techniques. In the present review, the authors discuss the unique properties of the primary motor area (M1), the dorsal portion of the premotor cortex (PMd), and the ventral portion of the premotor cortex (PMv). They end this review by discussing how the premotor areas influence M1.

  7. Intrahemispheric dysfunction in primary motor cortex without corpus callosum: a transcranial magnetic stimulation study

    PubMed Central

    Fecteau, Shirley; Lassonde, Maryse; Théoret, Hugo

    2006-01-01

    Background The two human cerebral hemispheres are continuously interacting, through excitatory and inhibitory influences and one critical structure subserving this interhemispheric balance is the corpus callosum. Interhemispheric neurophysiological abnormalities and intrahemispheric behavioral impairments have been reported in individuals lacking the corpus callosum. The aim of this study was to examine intrahemispheric neurophysiological function in primary motor cortex devoid of callosal projections. Methods Intracortical excitatory and inhibitory systems were tested in three individuals with complete agenesis of the corpus callosum and sixteen healthy individuals. These systems were assessed using transcranial magnetic stimulation (TMS) protocols: motor threshold at rest, paired-pulse curve, and cortical silent period. Results TMS revealed no difference between the patient and control groups on the motor threshold measure, as well as intracortical facilitation and intracortical inhibition systems as tested by paired stimulation. However, intrahemispheric inhibitory function was found to be abnormal in participants without callosal projections, as the cortical silent period duration was significantly increased in the patient group. Conclusion These data suggest that in addition to previously reported impaired interhemispheric function, patients lacking the entire corpus callosum also display abnormal intrahemispheric excitability of the primary motor cortex. PMID:16790050

  8. Activity in primary motor cortex during action observation covaries with subsequent behavioral changes in execution.

    PubMed

    Aridan, Nadav; Mukamel, Roy

    2016-11-01

    Observing someone else perform a movement facilitates motor planning, execution, and motor memory formation. Rate, an important feature in the execution of repeated movements, has been shown to vary following movement observation although the underlying neural mechanisms are unclear. In the current study, we examined how the rate of self-paced index finger pressing is implicitly modified following passive observation of a similar action performed at a different rate. Fifty subjects performed a finger pressing sequence with their right hand at their own pace before and after passive observation of either a 1-min video depicting the task performed at 3 Hz by someone else or a black screen. An additional set of 15 subjects performed the task in an MRI scanner. Across all 50 subjects, the spontaneous execution rate prior to video observation had a bimodal distribution with modes around 2 and 4 Hz. Following video observation, the slower subjects performed the task at an increased rate. In the 15 subjects who performed the task in the MRI scanner, we found positive correlation between fMRI signal in the left primary motor strip during passive video observation and subsequent behavioral changes in task performance rate. We conclude that observing someone else perform an action at a higher rate implicitly increases the spontaneous rate of execution, and that this implicit induction is mediated by activity in the contralateral primary motor cortex.

  9. Disruption of primary motor cortex before learning impairs memory of movement dynamics.

    PubMed

    Richardson, Andrew G; Overduin, Simon A; Valero-Cabré, Antoni; Padoa-Schioppa, Camillo; Pascual-Leone, Alvaro; Bizzi, Emilio; Press, Daniel Z

    2006-11-29

    Although multiple lines of evidence implicate the primary motor cortex (M1) in motor learning, the precise role of M1 in the adaptation to novel movement dynamics and in the subsequent consolidation of a memory of those dynamics remains unclear. Here we used repetitive transcranial magnetic stimulation (rTMS) to dissociate the contribution of M1 to these distinct aspects of motor learning. Subjects performed reaching movements in velocity-dependent force fields over three epochs: a null-field baseline epoch, a clockwise-field learning epoch (15 min after the baseline epoch), and a clockwise-field retest epoch (24 h after the learning epoch). Half of the subjects received 15 min of 1 Hz rTMS to M1 between the baseline and learning epochs. Subjects given rTMS performed identically to control subjects during the learning epoch. However, control subjects performed with significantly less error than rTMS subjects in the retest epoch on the following day. These results suggest that M1 is not critical to the network supporting motor adaptation per se but that, within this network, M1 may be important for initiating the development of long-term motor memories.

  10. Primary motor cortex functionally contributes to language comprehension: An online rTMS study.

    PubMed

    Vukovic, Nikola; Feurra, Matteo; Shpektor, Anna; Myachykov, Andriy; Shtyrov, Yury

    2017-02-01

    Among various questions pertinent to grounding human cognitive functions in a neurobiological substrate, the association between language and motor brain structures is a particularly debated one in neuroscience and psychology. While many studies support a broadly distributed model of language and semantics grounded, among other things, in the general modality-specific systems, theories disagree as to whether motor and sensory cortex activity observed during language processing is functional or epiphenomenal. Here, we assessed the role of motor areas in linguistic processing by investigating the responses of 28 healthy volunteers to different word types in semantic and lexical decision tasks, following repetitive transcranial magnetic stimulation (rTMS) of primary motor cortex. We found that early rTMS (delivered within 200ms of word onset) produces a left-lateralised and meaning-specific change in reaction speed, slowing down behavioural responses to action-related words, and facilitating abstract words - an effect present only during semantic, but not lexical, decision. We interpret these data in light of action-perception theory of language, bolstering the claim that motor cortical areas play a functional role in language comprehension. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Stimulus-response profile during single-pulse transcranial magnetic stimulation to the primary motor cortex.

    PubMed

    Hanakawa, Takashi; Mima, Tatsuya; Matsumoto, Riki; Abe, Mitsunari; Inouchi, Morito; Urayama, Shin-Ichi; Anami, Kimitaka; Honda, Manabu; Fukuyama, Hidenao

    2009-11-01

    We examined the stimulus-response profile during single-pulse transcranial magnetic stimulation (TMS) by measuring motor-evoked potentials (MEPs) with electromyographic monitoring and hemodynamic responses with functional magnetic resonance imaging (fMRI) at 3 Tesla. In 16 healthy subjects, single TMS pulses were irregularly delivered to the left primary motor cortex at a mean frequency of 0.15 Hz with a wide range of stimulus intensities. The measurement of MEP proved a typical relationship between stimulus intensity and MEP amplitude in the concurrent TMS-fMRI environment. In the population-level analysis of the suprathreshold stimulation conditions, significant increases in hemodynamic responses were detected in the motor/somatosensory network, reflecting both direct and remote effects of TMS, and also the auditory/cognitive areas, perhaps related to detection of clicks. The stimulus-response profile showed both linear and nonlinear components in the direct and remote motor/somatosensory network. A detailed analysis suggested that the nonlinear components of the motor/somatosensory network activity might be induced by nonlinear recruitment of neurons in addition to sensory afferents resulting from movement. These findings expand our basic knowledge of the quantitative relationship between TMS-induced neural activations and hemodynamic signals measured by neuroimaging techniques.

  12. Altered structural and functional connectivity between the bilateral primary motor cortex in unilateral subcortical stroke

    PubMed Central

    Zhang, Yong; Li, Kuang-Shi; Ning, Yan-Zhe; Fu, Cai-Hong; Liu, Hong-Wei; Han, Xiao; Cui, Fang-Yuan; Ren, Yi; Zou, Yi-Huai

    2016-01-01

    Abstract A large number of functional imaging studies have focused on the understanding of motor-related neural activities after ischemic stroke. However, the knowledge is still limited in the structural and functional changes of the interhemispheric connections of the bilateral primary motor cortices (M1s) and their potential influence on motor function recovery following stroke. Twenty-four stroke patients with right hemispheric subcortical infarcts and 25 control subjects were recruited to undergo multimodal magnetic resonance imaging examinations. Structural impairments between the bilateral M1s were measured by fractional anisotropy. Functional changes of the bilateral M1s were assessed via M1-M1 resting-state functional connectivity. Task-evoked activation analysis was applied to identify the roles of the bilateral hemispheres in motor function recovery. Compared with control subjects, unilateral subcortical stroke patients revealed significantly decreased fractional anisotropy and functional connectivity between the bilateral M1s. Stroke patients also revealed higher activations in multiple brain regions in both hemispheres and that more regions were located in the contralesional hemisphere. This study increased our understanding of the structural and functional alterations between the bilateral M1s that occur in unilateral subcortical stroke and provided further evidence for the compensatory role played by the contralesional hemisphere for these alterations during motor function recovery. PMID:27495109

  13. Cross-cultural aspects of depression management in primary care.

    PubMed

    Hails, Katherine; Brill, Charlotte D; Chang, Trina; Yeung, Albert; Fava, Maurizio; Trinh, Nhi-Ha

    2012-08-01

    Major depressive disorder (MDD) is a prevalent illness in minority populations. Minority patients with MDD are often unrecognized and untreated. This review examines promising interventions to address MDD in primary care settings, where minority groups are more likely to seek care. Since 2010, eleven interventions have been developed to address patient-specific and provider-specific barriers, many of which are adaptations of the collaborative care model. Other promising interventions include cultural tailoring of the collaborative care model, as well as the addition of telepsychiatry, motivational interviewing, cultural consultation, and innovations in interpreting. Overall, collaborative care was found feasible and improved satisfaction and treatment engagement of depressed minority patients in primary care. It remains inconclusive whether these newer intervention models improve MDD treatment outcomes. Future research will be needed to establish the effectiveness of these intervention models in improving the treatment outcomes of minority populations with MDD.

  14. Cross-cultural analysis of the motor development of Brazilian, Greek and Canadian infants assessed with the Alberta Infant Motor Scale

    PubMed Central

    Saccani, Raquel; Valentini, Nadia Cristina

    2013-01-01

    OBJECTIVE: To compare the motor development of infants from three population samples (Brazil, Canada and Greece), to investigate differences in the percentile curves of motor development in these samples, and to investigate the prevalence of motor delays in Brazilian children. METHODS: Observational, descriptive and cross-sectional study with 795 Brazilian infants from zero to 18 months of age, assessed by the Alberta Infant Motor Scale (AIMS) at day care centers, nurseries, basic health units and at home. The Brazilian infants' motor scores were compared to the results of two population samples from Greece (424 infants) and Canada (2,400 infants). Descriptive statistics was used, with one-sample t-test and binomial tests, being significant p≤0.05. RESULTS: 65.4% of Brazilian children showed typical motor development, although with lower mean scores. In the beginning of the second year of life, the differences in the motor development among Brazilian, Canadian and Greek infants were milder; at 15 months of age, the motor development became similar in the three groups. A non-linear motor development trend was observed. CONCLUSIONS: The lowest motor percentiles of the Brazilian sample emphasized the need for national norms in order to correctly categorize the infant motor development. The different ways of motor development may be a consequence of cultural differences in infant care. PMID:24142318

  15. Microbiologic and clinical value of primary broth cultures of wound specimens collected with swabs.

    PubMed Central

    Silletti, R P; Ailey, E; Sun, S; Tang, D

    1997-01-01

    In order to assess the microbiologic and clinical value of primary broth culture of wound specimens collected with swabs and submitted to the laboratory in transport medium, we compared the results of primary agar culture with the results of a corresponding primary broth culture for 344 aerobic specimens and 176 anaerobic specimens. While 8.7% (45 of 520) of the specimens yielded organisms from the primary broth culture that were not recovered from the corresponding primary agar culture, only 5.0% (26 of 520) of the specimens yielded organisms from the primary broth culture other than Staphylococcus epidermidis, viridans group streptococci, and Corynebacterium spp. Moreover, the primary broth culture of only 0.6% (3 of 520) of the specimens yielded organisms not recovered from the primary agar culture that caused a change in the therapy of the patient. Our conclusion is that primary broth cultures are unnecessary for the processing of wound specimens properly collected with swabs. PMID:9230370

  16. Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke.

    PubMed

    Peters, Denise M; Fridriksson, Julius; Stewart, Jill C; Richardson, Jessica D; Rorden, Chris; Bonilha, Leonardo; Middleton, Addie; Gleichgerrcht, Ezequiel; Fritz, Stacy L

    2017-10-05

    Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R(2)  = 0.36-0.46) and gait speed (R(2)  = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Primary Postnatal Dorsal Root Ganglion Culture from Conventionally Slaughtered Calves

    PubMed Central

    Fadda, A.; Bärtschi, M.; Hemphill, A.; Widmer, H. R.; Zurbriggen, A.; Perona, P.; Vidondo, B.; Oevermann, A.

    2016-01-01

    Neurological disorders in ruminants have an important impact on veterinary health, but very few host-specific in vitro models have been established to study diseases affecting the nervous system. Here we describe a primary neuronal dorsal root ganglia (DRG) culture derived from calves after being conventionally slaughtered for food consumption. The study focuses on the in vitro characterization of bovine DRG cell populations by immunofluorescence analysis. The effects of various growth factors on neuron viability, neurite outgrowth and arborisation were evaluated by morphological analysis. Bovine DRG neurons are able to survive for more than 4 weeks in culture. GF supplementation is not required for neuronal survival and neurite outgrowth. However, exogenously added growth factors promote neurite outgrowth. DRG cultures from regularly slaughtered calves represent a promising and sustainable host specific model for the investigation of pain and neurological diseases in bovines. PMID:27936156

  18. Organizational culture in the primary healthcare setting of Cyprus

    PubMed Central

    2013-01-01

    Background The concept of organizational culture is important in understanding the behaviour of individuals in organizations as they manage external demands and internal social changes. Cyprus healthcare system is under restructuring and soon a new healthcare scheme will be implemented starting at the Primary Healthcare (PHC) level. The aim of the study was to investigate the underlying culture encountered in the PHC setting of Cyprus and to identify possible differences in desired and prevailing cultures among healthcare professionals. Methods The population of the study included all general practitioners (GPs) and nursing staff working at the 42 PHC centres throughout the island. The shortened version of the Organizational Culture Profile questionnaire comprising 28 statements on organizational values was used in the study. The instrument was already translated and validated in Greek and cross-cultural adaptation was performed. Participants were required to indicate the organization’s characteristic cultural values orientation along a five-point Likert scale ranging from “Very Much = 1” to “Not at all= 5”. Statistical analysis was performed using SPSS 16.0. Student t-test was used to compare means between two groups of variables whereas for more than two groups analysis of variance (ANOVA) was applied. Results From the total of 306 healthcare professionals, 223 participated in the study (72.9%). The majority of participants were women (75.3%) and mean age was 42.6 ± 10.7 years. Culture dimension “performance orientation” was the desired culture among healthcare professionals (mean: 1.39 ± 0.45). “Supportiveness” and “social responsibility” were the main cultures encountered in PHC (means: 2.37 ± 0.80, 2.38 ± 0.83). Statistical significant differences were identified between desired and prevailing cultures for all culture dimensions (p= 0.000). Conclusions This was the first study performed in Cyprus assessing organizational culture in

  19. Organizational culture in the primary healthcare setting of Cyprus.

    PubMed

    Zachariadou, Theodora; Zannetos, Savvas; Pavlakis, Andreas

    2013-03-24

    The concept of organizational culture is important in understanding the behaviour of individuals in organizations as they manage external demands and internal social changes. Cyprus healthcare system is under restructuring and soon a new healthcare scheme will be implemented starting at the Primary Healthcare (PHC) level. The aim of the study was to investigate the underlying culture encountered in the PHC setting of Cyprus and to identify possible differences in desired and prevailing cultures among healthcare professionals. The population of the study included all general practitioners (GPs) and nursing staff working at the 42 PHC centres throughout the island. The shortened version of the Organizational Culture Profile questionnaire comprising 28 statements on organizational values was used in the study. The instrument was already translated and validated in Greek and cross-cultural adaptation was performed. Participants were required to indicate the organization's characteristic cultural values orientation along a five-point Likert scale ranging from "Very Much = 1" to "Not at all= 5". Statistical analysis was performed using SPSS 16.0. Student t-test was used to compare means between two groups of variables whereas for more than two groups analysis of variance (ANOVA) was applied. From the total of 306 healthcare professionals, 223 participated in the study (72.9%). The majority of participants were women (75.3%) and mean age was 42.6 ± 10.7 years. Culture dimension "performance orientation" was the desired culture among healthcare professionals (mean: 1.39 ± 0.45). "Supportiveness" and "social responsibility" were the main cultures encountered in PHC (means: 2.37 ± 0.80, 2.38 ± 0.83). Statistical significant differences were identified between desired and prevailing cultures for all culture dimensions (p= 0.000). This was the first study performed in Cyprus assessing organizational culture in the PHC setting. In the forthcoming health system reform

  20. CLINICAL, ENDOSCOPIC AND MANOMETRIC FEATURES OF THE PRIMARY MOTOR DISORDERS OF THE ESOPHAGUS

    PubMed Central

    MARTINEZ, Júlio César; LIMA, Gustavo Rosa de Almeida; SILVA, Diego Henrique; DUARTE, Alexandre Ferreira; NOVO, Neil Ferreira; da SILVA, Ernesto Carlos; PINTO, Pérsio Campos Correia; MAIA, Alexandre Moreira

    2015-01-01

    Background Significant incidence, diagnostic difficulties, clinical relevance and therapeutic efficacy associated with the small number of publications on the primary esophageal motor disorders, motivated the present study. Aim To determine the manometric prevalence of these disorders and correlate them to the endoscopic and clinical findings. Methods A retrospective study of 2614 patients, being 1529 (58.49%) women and 1085 (41.51%) men. From 299 manometric examinations diagnosed with primary esophageal motor disorder, were sought-clinical data (heartburn, regurgitation, dysphagia, odynophagia, non-cardiac chest pain, pharyngeal globe and extra-esophageal symptoms) and/or endoscopic (hiatal hernia, erosive esophagitis, food waste) that motivated the performance of manometry. Results Were found 49 cases of achalasia, 73 diffuse spasm, 89 nutcracker esophagus, 82 ineffective esophageal motility, and six lower esophageal sphincter hypertension. In relation to the correlations, it was observed that in 119 patients clinical conditions were associated with dysphagia, found in achalasia more than in other conditions; in relationship between endoscopic findings and clinical conditions there was no statistical significance between data. Conclusions The clinical and endoscopic findings have little value in the characterization of the primary motor disorders of the esophagus, showing even more the need for manometry, particularly in the preoperative period of gastroesophageal reflux disease. PMID:25861066

  1. Importance of culturing primary lymphocytes at physiological oxygen levels

    PubMed Central

    Atkuri, Kondala R.; Herzenberg, Leonard A.; Niemi, Anna-Kaisa; Cowan, Tina; Herzenberg, Leonore A.

    2007-01-01

    Although studies with primary lymphocytes are almost always conducted in CO2 incubators maintained at atmospheric oxygen levels (atmosO2; 20%), the physiological oxygen levels (physO2; 5%) that cells encounter in vivo are 2–4 times lower. We show here that culturing primary T cells at atmosO2 significantly alters the intracellular redox state (decreases intracellular glutathione, increases oxidized intracellular glutathione), whereas culturing at physO2 maintains the intracellular redox environment (intracellular glutathione/oxidized intracellular glutathione) close to its in vivo status. Furthermore, we show that CD3/CD28-induced T cell proliferation (based on proliferation index and cell yield) is higher at atmosO2 than at physO2. This apparently paradoxical finding, we suggest, may be explained by two additional findings with CD3/CD28-stimulated T cells: (i) the intracellular NO (iNO) levels are higher at physO2 than at atmosO2; and (ii) the peak expression of CD69 is significantly delayed and more sustained at physO2 that at atmosO2. Because high levels of intracellular NO and sustained CD69 tend to down-regulate T cell responses in vivo, the lower proliferative T cell responses at physO2 likely reflect the in vitro operation of the natural in vivo regulatory mechanisms. Thus, we suggest caution in culturing primary lymphocytes at atmosO2 because the requisite adaptation to nonphysiological oxygen levels may seriously skew T cell responses, particularly after several days in culture. PMID:17360561

  2. Effects of Ranolazine on Astrocytes and Neurons in Primary Culture.

    PubMed

    Aldasoro, Martin; Guerra-Ojeda, Sol; Aguirre-Rueda, Diana; Mauricio, M Dolores; Vila, Jose M; Marchio, Patricia; Iradi, Antonio; Aldasoro, Constanza; Jorda, Adrian; Obrador, Elena; Valles, Soraya L

    2016-01-01

    Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10-7, 10-6 and 10-5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on pro-inflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents.

  3. Effects of Ranolazine on Astrocytes and Neurons in Primary Culture

    PubMed Central

    Aldasoro, Martin; Guerra-Ojeda, Sol; Aguirre-Rueda, Diana; Mauricio, Mª Dolores; Vila, Jose Mª; Marchio, Patricia; Iradi, Antonio; Aldasoro, Constanza; Jorda, Adrian; Obrador, Elena; Valles, Soraya L.

    2016-01-01

    Ranolazine (Rn) is an antianginal agent used for the treatment of chronic angina pectoris when angina is not adequately controlled by other drugs. Rn also acts in the central nervous system and it has been proposed for the treatment of pain and epileptic disorders. Under the hypothesis that ranolazine could act as a neuroprotective drug, we studied its effects on astrocytes and neurons in primary culture. We incubated rat astrocytes and neurons in primary cultures for 24 hours with Rn (10−7, 10−6 and 10−5 M). Cell viability and proliferation were measured using trypan blue exclusion assay, MTT conversion assay and LDH release assay. Apoptosis was determined by Caspase 3 activity assay. The effects of Rn on pro-inflammatory mediators IL-β and TNF-α was determined by ELISA technique, and protein expression levels of Smac/Diablo, PPAR-γ, Mn-SOD and Cu/Zn-SOD by western blot technique. In cultured astrocytes, Rn significantly increased cell viability and proliferation at any concentration tested, and decreased LDH leakage, Smac/Diablo expression and Caspase 3 activity indicating less cell death. Rn also increased anti-inflammatory PPAR-γ protein expression and reduced pro-inflammatory proteins IL-1 β and TNFα levels. Furthermore, antioxidant proteins Cu/Zn-SOD and Mn-SOD significantly increased after Rn addition in cultured astrocytes. Conversely, Rn did not exert any effect on cultured neurons. In conclusion, Rn could act as a neuroprotective drug in the central nervous system by promoting astrocyte viability, preventing necrosis and apoptosis, inhibiting inflammatory phenomena and inducing anti-inflammatory and antioxidant agents. PMID:26950436

  4. Culturing primary rat inner medullary collecting duct cells.

    PubMed

    Faust, Dörte; Geelhaar, Andrea; Eisermann, Beate; Eichhorst, Jenny; Wiesner, Burkhard; Rosenthal, Walter; Klussmann, Enno; Klussman, Enno

    2013-06-21

    Arginine-vasopressin (AVP) facilitates water reabsorption by renal collecting duct principal cells and thereby fine-tunes body water homeostasis. AVP binds to vasopressin V2 receptors (V2R) on the surface of the cells and thereby induces synthesis of cAMP. This stimulates cellular signaling processes leading to changes in the phosphorylation of the water channel aquaporin-2 (AQP2). Protein kinase A phoshorylates AQP2 and thereby triggers the translocation of AQP2 from intracellular vesicles into the plasma membrane facilitating water reabsorption from primary urine. Aberrations of AVP release from the pituitary or AVP-activated signaling in principal cells can cause central or nephrogenic diabetes insipidus, respectively; an elevated blood plasma AVP level is associated with cardiovascular diseases such as chronic heart failure and the syndrome of inappropriate antidiuretic hormone secretion. Here, we present a protocol for cultivation of primary rat inner medullary collecting duct (IMCD) cells, which express V2R and AQP2 endogenously. The cells are suitable for elucidating molecular mechanisms underlying the control of AQP2 and thus to discover novel drug targets for the treatment of diseases associated with dysregulation of AVP-mediated water reabsorption. IMCD cells are obtained from rat renal inner medullae and are used for experiments six to eight days after seeding. IMCD cells can be cultured in regular cell culture dishes, flasks and micro-titer plates of different formats, the procedure only requires a few hours, and is appropriate for standard cell culture laboratories.

  5. Culturing Primary Rat Inner Medullary Collecting Duct Cells

    PubMed Central

    Faust, Dörte; Geelhaar, Andrea; Eisermann, Beate; Eichhorst, Jenny; Wiesner, Burkhard; Rosenthal, Walter; Klussman, Enno

    2013-01-01

    Arginine-vasopressin (AVP) facilitates water reabsorption by renal collecting duct principal cells and thereby fine-tunes body water homeostasis. AVP binds to vasopressin V2 receptors (V2R) on the surface of the cells and thereby induces synthesis of cAMP. This stimulates cellular signaling processes leading to changes in the phosphorylation of the water channel aquaporin-2 (AQP2). Protein kinase A phoshorylates AQP2 and thereby triggers the translocation of AQP2 from intracellular vesicles into the plasma membrane facilitating water reabsorption from primary urine. Aberrations of AVP release from the pituitary or AVP-activated signaling in principal cells can cause central or nephrogenic diabetes insipidus, respectively; an elevated blood plasma AVP level is associated with cardiovascular diseases such as chronic heart failure and the syndrome of inappropriate antidiuretic hormone secretion. Here, we present a protocol for cultivation of primary rat inner medullary collecting duct (IMCD) cells, which express V2R and AQP2 endogenously. The cells are suitable for elucidating molecular mechanisms underlying the control of AQP2 and thus to discover novel drug targets for the treatment of diseases associated with dysregulation of AVP-mediated water reabsorption. IMCD cells are obtained from rat renal inner medullae and are used for experiments six to eight days after seeding. IMCD cells can be cultured in regular cell culture dishes, flasks and micro-titer plates of different formats, the procedure only requires a few hours, and is appropriate for standard cell culture laboratories. PMID:23852264

  6. Mirror illusion reduces motor cortical inhibition in the ipsilateral primary motor cortex during forceful unilateral muscle contractions.

    PubMed

    Zult, Tjerk; Goodall, Stuart; Thomas, Kevin; Hortobágyi, Tibor; Howatson, Glyn

    2015-04-01

    Forceful, unilateral contractions modulate corticomotor paths targeting the resting, contralateral hand. However, it is unknown whether mirror-viewing of a slowly moving but forcefully contracting hand would additionally affect these paths. Here we examined corticospinal excitability and short-interval intracortical inhibition (SICI) of the right-ipsilateral primary motor cortex (M1) in healthy young adults under no-mirror and mirror conditions at rest and during right wrist flexion at 60% maximal voluntary contraction (MVC). During the no-mirror conditions neither hand was visible, whereas in the mirror conditions participants looked at the right hand's reflection in the mirror. Corticospinal excitability increased during contractions in the left flexor carpi radialis (FCR) (contraction 0.41 mV vs. rest 0.21 mV) and extensor carpi radialis (ECR) (contraction 0.56 mV vs. rest 0.39 mV), but there was no mirror effect (FCR: P = 0.743, ηp (2) = 0.005; ECR: P = 0.712, ηp (2) = 0.005). However, mirror-viewing of the contracting and moving wrist attenuated SICI relative to test pulse in the left FCR by ∼9% compared with the other conditions (P < 0.05, d ≥ 0.62). Electromyographic activity in the resting left hand prior to stimulation was not affected by the mirror (FCR: P = 0.255, ηp (2) = 0.049; ECR: P = 0.343, ηp (2) = 0.035) but increased twofold during contractions. Thus viewing the moving hand in the mirror and not just the mirror image of the nonmoving hand seems to affect motor cortical inhibitory networks in the M1 associated with the mirror image. Future studies should determine whether the use of a mirror could increase interlimb transfer produced by cross-education, especially in patient groups with unilateral orthopedic and neurological conditions.

  7. Mirror illusion reduces motor cortical inhibition in the ipsilateral primary motor cortex during forceful unilateral muscle contractions

    PubMed Central

    Goodall, Stuart; Thomas, Kevin; Hortobágyi, Tibor; Howatson, Glyn

    2015-01-01

    Forceful, unilateral contractions modulate corticomotor paths targeting the resting, contralateral hand. However, it is unknown whether mirror-viewing of a slowly moving but forcefully contracting hand would additionally affect these paths. Here we examined corticospinal excitability and short-interval intracortical inhibition (SICI) of the right-ipsilateral primary motor cortex (M1) in healthy young adults under no-mirror and mirror conditions at rest and during right wrist flexion at 60% maximal voluntary contraction (MVC). During the no-mirror conditions neither hand was visible, whereas in the mirror conditions participants looked at the right hand's reflection in the mirror. Corticospinal excitability increased during contractions in the left flexor carpi radialis (FCR) (contraction 0.41 mV vs. rest 0.21 mV) and extensor carpi radialis (ECR) (contraction 0.56 mV vs. rest 0.39 mV), but there was no mirror effect (FCR: P = 0.743, ηp2 = 0.005; ECR: P = 0.712, ηp2 = 0.005). However, mirror-viewing of the contracting and moving wrist attenuated SICI relative to test pulse in the left FCR by ∼9% compared with the other conditions (P < 0.05, d ≥ 0.62). Electromyographic activity in the resting left hand prior to stimulation was not affected by the mirror (FCR: P = 0.255, ηp2 = 0.049; ECR: P = 0.343, ηp2 = 0.035) but increased twofold during contractions. Thus viewing the moving hand in the mirror and not just the mirror image of the nonmoving hand seems to affect motor cortical inhibitory networks in the M1 associated with the mirror image. Future studies should determine whether the use of a mirror could increase interlimb transfer produced by cross-education, especially in patient groups with unilateral orthopedic and neurological conditions. PMID:25632077

  8. An unavoidable modulation? Sensory attention and human primary motor cortex excitability.

    PubMed

    Ruge, Diane; Muggleton, Neil; Hoad, Damon; Caronni, Antonio; Rothwell, John C

    2014-09-01

    The link between basic physiology and its modulation by cognitive states, such as attention, is poorly understood. A significant association becomes apparent when patients with movement disorders describe experiences with changing their attention focus and the fundamental effect that this has on their motor symptoms. Moreover, frequently used mental strategies for treating such patients, e.g. with task-specific dystonia, widely lack laboratory-based knowledge about physiological mechanisms. In this largely unexplored field, we looked at how the locus of attention, when it changed between internal (locus hand) and external (visual target), influenced excitability in the primary motor cortex (M1) in healthy humans. Intriguingly, both internal and external attention had the capacity to change M1 excitability. Both led to a reduced stimulation-induced GABA-related inhibition and a change in motor evoked potential size, i.e. an overall increased M1 excitability. These previously unreported findings indicated: (i) that cognitive state differentially interacted with M1 physiology, (ii) that our view of distraction (attention locus shifted towards external or distant location), which is used as a prevention or management strategy for use-dependent motor disorders, is too simple and currently unsupported for clinical application, and (iii) the physiological state reached through attention modulation represents an alternative explanation for frequently reported electrophysiology findings in neuropsychiatric disorders, such as an aberrant inhibition.

  9. Spatiotemporal relations of primary sensorimotor and secondary motor activation patterns mapped by NIR imaging

    PubMed Central

    Khan, Bilal; Chand, Pankaj; Alexandrakis, George

    2011-01-01

    Functional near infrared (fNIR) imaging was used to identify spatiotemporal relations between spatially distinct cortical regions activated during various hand and arm motion protocols. Imaging was performed over a field of view (FOV, 12 x 8.4 cm) including the secondary motor, primary sensorimotor, and the posterior parietal cortices over a single brain hemisphere. This is a more extended FOV than typically used in current fNIR studies. Three subjects performed four motor tasks that induced activation over this extended FOV. The tasks included card flipping (pronation and supination) that, to our knowledge, has not been performed in previous functional magnetic resonance imaging (fMRI) or fNIR studies. An earlier rise and a longer duration of the hemodynamic activation response were found in tasks requiring increased physical or mental effort. Additionally, analysis of activation images by cluster component analysis (CCA) demonstrated that cortical regions can be grouped into clusters, which can be adjacent or distant from each other, that have similar temporal activation patterns depending on whether the performed motor task is guided by visual or tactile feedback. These analyses highlight the future potential of fNIR imaging to tackle clinically relevant questions regarding the spatiotemporal relations between different sensorimotor cortex regions, e.g. ones involved in the rehabilitation response to motor impairments. PMID:22162826

  10. Continuous Force Decoding from Local Field Potentials of the Primary Motor Cortex in Freely Moving Rats

    PubMed Central

    Khorasani, Abed; Heydari Beni, Nargess; Shalchyan, Vahid; Daliri, Mohammad Reza

    2016-01-01

    Local field potential (LFP) signals recorded by intracortical microelectrodes implanted in primary motor cortex can be used as a high informative input for decoding of motor functions. Recent studies show that different kinematic parameters such as position and velocity can be inferred from multiple LFP signals as precisely as spiking activities, however, continuous decoding of the force magnitude from the LFP signals in freely moving animals has remained an open problem. Here, we trained three rats to press a force sensor for getting a drop of water as a reward. A 16-channel micro-wire array was implanted in the primary motor cortex of each trained rat, and obtained LFP signals were used for decoding of the continuous values recorded by the force sensor. Average coefficient of correlation and the coefficient of determination between decoded and actual force signals were r = 0.66 and R2 = 0.42, respectively. We found that LFP signal on gamma frequency bands (30–120 Hz) had the most contribution in the trained decoding model. This study suggests the feasibility of using low number of LFP channels for the continuous force decoding in freely moving animals resembling BMI systems in real life applications. PMID:27767063

  11. Seizure outcome following primary motor cortex-sparing resective surgery for perirolandic focal cortical dysplasia.

    PubMed

    Gopinath, Siby; Roy, Arun Grace; Vinayan, Kollencheri Puthenveetil; Kumar, Anand; Sarma, Manjit; Rajeshkannan, Ramiah; Pillai, Ashok

    2016-12-01

    We present a case series of patients who underwent perirolandic resection for medically refractory focal epilepsy due to focal cortical dysplasia (FCD). Our aim was to specifically evaluate the outcome of a surgical strategy intended for seizure freedom while preserving primary motor cortex function. Thirteen patients undergoing perirolandic resection for pharmacoresistant focal epilepsy between 2010 and 2015 who demonstrated histological evidence of FCD were selected from a prospectively maintained database. Presurgical evaluation included video EEG telemetry and 3T MRI brain for all patients. Eight patients underwent interictal FDG PET scan. Intracranial EEG monitoring was done for 8 patients - six by conventional subdural grid and depth electrodes and two by Stereo EEG. Additional techniques included extraoperative cortical stimulation mapping, intraoperative electrocorticography (ECoG), intraoperative motor cortex mapping and awake surgery in various combinations. In all cases (lesional and nonlesional), resection was intentionally limited for anatomic preservation of the primary motor cortex. Amongst the thirteen patients with age ranging 14-44 years (mean 26.8 ± 9.2) 62% of them had daily seizures. MRI abnormalities were identified in 8 patients (62%), PET showed concordant findings in 7 patients (88%). When utilized, the mean duration of intracranial EEG recordings was 8.0 ± 7.2 days (range 2-23 days). All patients underwent a primary motor cortex-sparing resection of the suspected epileptogenic cortex. The mean postoperative follow up period was 23 months (range 7.5-62 months). Twelve out of 13 (92%) were seizure free (Engel 1) outcome at the last follow-up assessment; one patient had Engel 2a outcome at 28 months. Six patients (46%) had immediate new focal neurological deficits, however all six patients had recovered completely within three months. The surgical strategy of a primary motor cortex-sparing resective surgery for perirolandic FCD is

  12. Cross-cultural comparison of motor competence in children from Australia and Belgium

    PubMed Central

    Bardid, Farid; Rudd, James R.; Lenoir, Matthieu; Polman, Remco; Barnett, Lisa M.

    2015-01-01

    Motor competence in childhood is an important determinant of physical activity and physical fitness in later life. However, childhood competence levels in many countries are lower than desired. Due to the many different motor skill instruments in use, children's motor competence across countries is rarely compared. The purpose of this study was to evaluate the motor competence of children from Australia and Belgium using the Körperkoordinationstest für Kinder (KTK). The sample consisted of 244 (43.4% boys) Belgian children and 252 (50.0% boys) Australian children, aged 6–8 years. A MANCOVA for the motor scores showed a significant country effect. Belgian children scored higher on jumping sideways, moving sideways and hopping for height but not for balancing backwards. Moreover, a Chi squared test revealed significant differences between the Belgian and Australian score distribution with 21.3% Belgian and 39.3% Australian children scoring “below average.” The very low levels reported by Australian children may be the result of cultural differences in physical activity contexts such as physical education and active transport. When compared to normed scores, both samples scored significantly worse than children 40 years ago. The decline in children's motor competence is a global issue, largely influenced by increasing sedentary behavior and a decline in physical activity. PMID:26217282

  13. Cross-cultural comparison of motor competence in children from Australia and Belgium.

    PubMed

    Bardid, Farid; Rudd, James R; Lenoir, Matthieu; Polman, Remco; Barnett, Lisa M

    2015-01-01

    Motor competence in childhood is an important determinant of physical activity and physical fitness in later life. However, childhood competence levels in many countries are lower than desired. Due to the many different motor skill instruments in use, children's motor competence across countries is rarely compared. The purpose of this study was to evaluate the motor competence of children from Australia and Belgium using the Körperkoordinationstest für Kinder (KTK). The sample consisted of 244 (43.4% boys) Belgian children and 252 (50.0% boys) Australian children, aged 6-8 years. A MANCOVA for the motor scores showed a significant country effect. Belgian children scored higher on jumping sideways, moving sideways and hopping for height but not for balancing backwards. Moreover, a Chi squared test revealed significant differences between the Belgian and Australian score distribution with 21.3% Belgian and 39.3% Australian children scoring "below average." The very low levels reported by Australian children may be the result of cultural differences in physical activity contexts such as physical education and active transport. When compared to normed scores, both samples scored significantly worse than children 40 years ago. The decline in children's motor competence is a global issue, largely influenced by increasing sedentary behavior and a decline in physical activity.

  14. Primary motor and premotor cortex in implicit sequence learning--evidence for competition between implicit and explicit human motor memory systems.

    PubMed

    Kantak, Shailesh S; Mummidisetty, Chaithanya K; Stinear, James W

    2012-09-01

    Implicit and explicit memory systems for motor skills compete with each other during and after motor practice. Primary motor cortex (M1) is known to be engaged during implicit motor learning, while dorsal premotor cortex (PMd) is critical for explicit learning. To elucidate the neural substrates underlying the interaction between implicit and explicit memory systems, adults underwent a randomized crossover experiment of anodal transcranial direct current stimulation (AtDCS) applied over M1, PMd or sham stimulation during implicit motor sequence (serial reaction time task, SRTT) practice. We hypothesized that M1-AtDCS during practice will enhance online performance and offline learning of the implicit motor sequence. In contrast, we also hypothesized that PMd-AtDCS will attenuate performance and retention of the implicit motor sequence. Implicit sequence performance was assessed at baseline, at the end of acquisition (EoA), and 24 h after practice (retention test, RET). M1-AtDCS during practice significantly improved practice performance and supported offline stabilization compared with Sham tDCS. Performance change from EoA to RET revealed that PMd-AtDCS during practice attenuated offline stabilization compared with M1-AtDCS and sham stimulation. The results support the role of M1 in implementing online performance gains and offline stabilization for implicit motor sequence learning. In contrast, enhancing the activity within explicit motor memory network nodes such as the PMd during practice may be detrimental to offline stabilization of the learned implicit motor sequence. These results support the notion of competition between implicit and explicit motor memory systems and identify underlying neural substrates that are engaged in this competition. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  15. Effect of primary culture medium type for culture of canine fibroblasts on production of cloned dogs.

    PubMed

    Kim, Geon A; Oh, Hyun Ju; Kim, Min Jung; Jo, Young Kwang; Choi, Jin; Kim, Jin Wook; Lee, Tae Hee; Lee, Byeong Chun

    2015-09-01

    Fibroblasts are common source of donor cells for SCNT. It is suggested that donor cells' microenvironment, including the primary culture, affects development of reconstructed embryos. To prove this, canine embryos were cloned with fibroblasts that were cultured in two different primary media (RCMEp vs. Dulbecco's modified Eagle's medium [DMEM]) and in vivo developments were compared with relative amount of stemness, reprogramming, apoptosis gene transcripts, and telomerase activity. Donor cells cultured in RCMEp contained a significantly higher amount of SOX2, NANOG, DPPA2, REXO1, HDAC, DNMT1, MECP2 and telomerase activity than those cultured in DMEM (P < 0.05). In vivo developmental potential of cloned embryos with donor cells cultured in RCMEp had a higher birth rate than that of embryos derived from DMEM (P < 0.05). The culture medium can induce changes in gene expression of donor cells and telomerase activity, and these alterations can also affect in vivo developmental competence of the cloned embryos.

  16. Insulin Cannot Induce Adipogenic Differentiation in Primary Cardiac Cultures

    PubMed Central

    Parameswaran, Sreejit; Sharma, Rajendra K.

    2016-01-01

    Cardiac tissue contains a heterogeneous population of cardiomyocytes and nonmyocyte population especially fibroblasts. Fibroblast differentiation into adipogenic lineage is important for fat accumulation around the heart which is important in cardiac pathology. The differentiation in fibroblast has been observed both spontaneously and due to increased insulin stimulation. The present study aims to observe the effect of insulin in adipogenic differentiation of cardiac cells present in primary murine cardiomyocyte cultures. Oil Red O (ORO) staining has been used for observing the lipid accumulations formed due to adipogenic differentiation in murine cardiomyocyte cultures. The accumulated lipids were quantified by ORO assay and normalized using protein estimation. The lipid accumulation in cardiac cultures did not increase in presence of insulin. However, addition of other growth factors like insulin-like growth factor 1 and epidermal growth factor promoted adipogenic differentiation even in the presence of insulin and other inhibitory molecules such as vitamins. Lipid accumulation also increased in cells grown in media without insulin after an initial exposure to insulin-containing growth media. The current study adds to the existing knowledge that the insulin by itself cannot induce adipogenic induction in the cardiac cultures. The data have significance in the understanding of cardiovascular health especially in diabetic patients. PMID:27574386

  17. In vitro methods to culture primary human breast epithelial cells.

    PubMed

    Raouf, Afshin; Sun, Yu Jia

    2013-01-01

    Current evidence suggests that much like leukemia, breast tumors are maintained by a small subpopulation of tumor cells that have stem cell properties. These cancer stem cells are envisaged to be responsible for tumor formation and relapse. Therefore, knowledge about their nature will provide a platform to develop therapies to eliminate these breast cancer stem cells. This concept highlights the need to understand the mechanisms that regulate the normal functions of the breast stem cells and their immediate progeny as alterations to these same mechanisms can cause these primitive cells to act as cancer stem cells. The study of the primitive cell functions relies on the ability to isolate them from primary sources of breast tissue. This chapter describes processing of discarded tissue from reduction mammoplasty samples as sources of normal primary human breast epithelial cells and describes cell culture systems to grow single-cell suspensions prepared from these reduction samples in vitro.

  18. Cingulate cortical cells projecting to monkey frontal eye field and primary motor cortex.

    PubMed

    Wang, Yan; Matsuzaka, Yoshiya; Shima, Keisetsu; Tanji, Jun

    2004-07-19

    We compared the distribution of cingulate cortical cells projecting to the frontal eye field (FEF) and primary motor cortex (MI) using a multiple retrograde labeling technique. Two fluorescent tracers were injected into physiologically identified FEF and MI in each monkey. The location of cells projecting to the forelimb area of MI served to identify the rostral (CMAr) and caudal (CMAc) cingulate motor areas. We found two foci of cells projecting to the FEF: rostral (CEFr) and caudal (CEFc) cingulate eye field. The CEFr was located rostral to the CMAr, while the CEFc was located rostro-ventral to the CMAc. Cells projecting to the FEF and MI scarcely overlapped, indicating that each area receives different sets of information from the cingulate cortex.

  19. Primary cell cultures of bovine colon epithelium: isolation and cell culture of colonocytes.

    PubMed

    Föllmann, W; Weber, S; Birkner, S

    2000-10-01

    Epithelial cells from bovine colon were isolated by mechanical preparation combined with an enzymatic digestion from colon specimens derived from freshly slaughtered animals. After digestion with collagenase I, the isolated tissue was centrifuged on a 2% D-sorbitol gradient to separate epithelial crypts which were seeded in collagen I-coated culture flasks. By using colon crypts and omitting the seeding of single cells a contamination by fibroblasts was prevented. The cells proliferated under the chosen culture conditions and formed monolayer cultures which were maintained for several weeks, including subcultivation steps. A population doubling time of about 21 hr was estimated in the log phase of the corresponding growth curve. During the culture period the cells were characterized morphologically and enzymatically. By using antibodies against cytokeratine 7 and 13 the isolated cells were identified as cells of epithelial origin. Antibodies against vimentin served as negative control. Morphological features such as microvilli, desmosomes and tight junctions, which demonstrated the ability of the cultured cells to restore an epithelial like monolayer, were shown by ultrastructural investigations. The preservation of the secretory function of the cultured cells was demonstrated by mucine cytochemistry with alcian blue staining. A stable expression of enzyme activities over a period of 6 days in culture occurred for gamma-glutamyltranspeptidase, acid phosphatase and NADH-dehydrogenase activity under the chosen culture conditions. Activity of alkaline phosphatase decreased to about 50% of basal value after 6 days in culture. Preliminary estimations of the metabolic competence of these cells revealed cytochrome P450 1A1-associated EROD activity in freshly isolated cells which was stable over 5 days in cultured cells. Then activity decreased completely. This culture system with primary epithelial cells from the colon will be used further as a model for the colon

  20. Error-enhancing robot therapy to induce motor control improvement in childhood onset primary dystonia.

    PubMed

    Casellato, Claudia; Pedrocchi, Alessandra; Zorzi, Giovanna; Rizzi, Giorgio; Ferrigno, Giancarlo; Nardocci, Nardo

    2012-07-23

    Robot-generated deviating forces during multijoint reaching movements have been applied to investigate motor control and to tune neuromotor adaptation. Can the application of force to limbs improve motor learning? In this framework, the response to altered dynamic environments of children affected by primary dystonia has never been studied. As preliminary pilot study, eleven children with primary dystonia and eleven age-matched healthy control subjects were asked to perform upper limb movements, triangle-reaching (three directions) and circle-writing, using a haptic robot interacting with ad-hoc developed task-specific visual interfaces. Three dynamic conditions were provided, null additive external force (A), constant disturbing force (B) and deactivation of the additive external force again (C). The path length for each trial was computed, from the recorded position data and interaction events. The results show that the disturbing force affects significantly the movement outcomes in healthy but not in dystonic subjects, already compromised in the reference condition: the external alteration uncalibrates the healthy sensorimotor system, while the dystonic one is already strongly uncalibrated. The lack of systematic compensation for perturbation effects during B condition is reflected into the absence of after-effects in C condition, which would be the evidence that CNS generates a prediction of the perturbing forces using an internal model of the environment.The most promising finding is that in dystonic population the altered dynamic exposure seems to induce a subsequent improvement, i.e. a beneficial after-effect in terms of optimal path control, compared with the correspondent reference movement outcome. The short-time error-enhancing training in dystonia could represent an effective approach for motor performance improvement, since the exposure to controlled dynamic alterations induces a refining of the existing but strongly imprecise motor scheme and

  1. Stimulation over primary motor cortex during action observation impairs effector recognition.

    PubMed

    Naish, Katherine R; Barnes, Brittany; Obhi, Sukhvinder S

    2016-04-01

    Recent work suggests that motor cortical processing during action observation plays a role in later recognition of the object involved in the action. Here, we investigated whether recognition of the effector making an action is also impaired when transcranial magnetic stimulation (TMS) - thought to interfere with normal cortical activity - is applied over the primary motor cortex (M1) during action observation. In two experiments, single-pulse TMS was delivered over the hand area of M1 while participants watched short clips of hand actions. Participants were then asked whether an image (experiment 1) or a video (experiment 2) of a hand presented later in the trial was the same or different to the hand in the preceding video. In Experiment 1, we found that participants' ability to recognise static images of hands was significantly impaired when TMS was delivered over M1 during action observation, compared to when no TMS was delivered, or when stimulation was applied over the vertex. Conversely, stimulation over M1 did not affect recognition of dot configurations, or recognition of hands that were previously presented as static images (rather than action movie clips) with no object. In Experiment 2, we found that effector recognition was impaired when stimulation was applied part way through (300ms) and at the end (500ms) of the action observation period, indicating that 200ms of action-viewing following stimulation was not long enough to form a new representation that could be used for later recognition. The findings of both experiments suggest that interfering with cortical motor activity during action observation impairs subsequent recognition of the effector involved in the action, which complements previous findings of motor system involvement in object memory. This work provides some of the first evidence that motor processing during action observation is involved in forming representations of the effector that are useful beyond the action observation period.

  2. Primary motor cortex of the parkinsonian monkey: altered encoding of active movement

    PubMed Central

    Pasquereau, Benjamin; DeLong, Mahlon R.

    2016-01-01

    Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson’s disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (−22%), speed (−40%), acceleration (−49%) and hand position (−33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (−50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes

  3. Primary motor cortex of the parkinsonian monkey: altered encoding of active movement.

    PubMed

    Pasquereau, Benjamin; DeLong, Mahlon R; Turner, Robert S

    2016-01-01

    Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson's disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (-22%), speed (-40%), acceleration (-49%) and hand position (-33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (-50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes beginning in the 150

  4. Fine Motor Skills Predict Maths Ability Better than They Predict Reading Ability in the Early Primary School Years.

    PubMed

    Pitchford, Nicola J; Papini, Chiara; Outhwaite, Laura A; Gulliford, Anthea

    2016-01-01

    Fine motor skills have long been recognized as an important foundation for development in other domains. However, more precise insights into the role of fine motor skills, and their relationships to other skills in mediating early educational achievements, are needed to support the development of optimal educational interventions. We explored concurrent relationships between two components of fine motor skills, Fine Motor Precision and Fine Motor Integration, and early reading and maths development in two studies with primary school children of low-to-mid socio-economic status in the UK. Two key findings were revealed. First, despite being in the first 2 years of primary school education, significantly better performance was found in reading compared to maths across both studies. This may reflect the protective effects of recent national-level interventions to promote early literacy skills in young children in the UK that have not been similarly promoted for maths. Second, fine motor skills were a better predictor of early maths ability than they were of early reading ability. Hierarchical multiple regression revealed that fine motor skills did not significantly predict reading ability when verbal short-term memory was taken into account. In contrast, Fine Motor Integration remained a significant predictor of maths ability, even after the influence of non-verbal IQ had been accounted for. These results suggest that fine motor skills should have a pivotal role in educational interventions designed to support the development of early mathematical skills.

  5. Fine Motor Skills Predict Maths Ability Better than They Predict Reading Ability in the Early Primary School Years

    PubMed Central

    Pitchford, Nicola J.; Papini, Chiara; Outhwaite, Laura A.; Gulliford, Anthea

    2016-01-01

    Fine motor skills have long been recognized as an important foundation for development in other domains. However, more precise insights into the role of fine motor skills, and their relationships to other skills in mediating early educational achievements, are needed to support the development of optimal educational interventions. We explored concurrent relationships between two components of fine motor skills, Fine Motor Precision and Fine Motor Integration, and early reading and maths development in two studies with primary school children of low-to-mid socio-economic status in the UK. Two key findings were revealed. First, despite being in the first 2 years of primary school education, significantly better performance was found in reading compared to maths across both studies. This may reflect the protective effects of recent national-level interventions to promote early literacy skills in young children in the UK that have not been similarly promoted for maths. Second, fine motor skills were a better predictor of early maths ability than they were of early reading ability. Hierarchical multiple regression revealed that fine motor skills did not significantly predict reading ability when verbal short-term memory was taken into account. In contrast, Fine Motor Integration remained a significant predictor of maths ability, even after the influence of non-verbal IQ had been accounted for. These results suggest that fine motor skills should have a pivotal role in educational interventions designed to support the development of early mathematical skills. PMID:27303342

  6. Histological-MRI correlation in the primary motor cortex of patients with amyotrophic lateral sclerosis.

    PubMed

    Meadowcroft, Mark D; Mutic, Nathan J; Bigler, Don C; Wang, Jian-Li; Simmons, Zachary; Connor, James R; Yang, Qing X

    2015-03-01

    To establish the relationship between ALS histopathology and quantitative MRI metrics. ALS patients (N = 8) in advanced stages of the disease were enrolled and, immediately after death, the brain of each patient was removed. Freshly excised ALS tissue was imaged at 3.0 Tesla with T1 and T2 mapping protocols and subsequently stained with astrocyte, myelin, and neuronal markers. Measures of ALS histological stains were compared with the internal control (primary visual cortex) and longitudinal parametric maps. Post-mortem T1 -weighted images demonstrate diminished contrast between gray and white matter and alterations in T1 relaxation within the primary motor cortex. An increase in astrocyte number and reactivity as well as evident neuronal loss, a decrease in axonal density, and unraveling of the myelin sheaths in subcortical white matter were found in the ALS primary motor cortex exhibiting significant T1 relaxation and contrast changes. This study provides a histopathological basis for differences in MR T1 contrast and relaxation seen in the ALS brain. © 2014 Wiley Periodicals, Inc.

  7. Motor training and the combination of action observation and peripheral nerve stimulation reciprocally interfere with the plastic changes induced in primary motor cortex excitability.

    PubMed

    Bisio, Ambra; Avanzino, Laura; Biggio, Monica; Ruggeri, Piero; Bove, Marco

    2017-04-21

    AO-PNS is a stimulation protocol combining action observation (AO) and peripheral nerve stimulation (PNS) to induce plasticity in the primary motor cortex (M1) (increased excitability). Another method to increase M1 excitability is motor training. The combination of two protocols, which individually induce long-term potentiation (LTP)-like plasticity in overlapping neural circuits, results in a transitory occlusion or reverse of this phenomenon. This study aimed to understand the neurophysiological mechanisms underlying AO-PNS by testing whether AO-PNS and motor training induced LTP-like plasticity in, at least partially, overlapping neural networks. One group of participants practiced a motor training (finger opposition movements) followed by AO-PNS, whereas another group performed the two protocols in reverse order. Motor performance was evaluated by means of a sensor-engineered glove and transcranial magnetic stimulation was used to assess M1 excitability before and after each conditioning protocol. Motor training increased movement frequency, suggesting the occurrence of motor learning in both groups. When applied on first, both motor training and AO-PNS significantly increased the motor-evoked potential (MEP), but occluded the increase of cortical excitability expected after the following protocol, leading to a significant decrease of MEP amplitude. These results suggest that motor training and AO-PNS act on partially overlapping neuronal networks, which include M1, and that AO-PNS might be able to induce LTP-like plasticity in a similar way to overt movement execution. This candidates AO-PNS as methodology potentially useful when planning rehabilitative interventions on patients who cannot voluntarily move.

  8. Toxicity of redox cycling pesticides in primary mesencephalic cultures.

    PubMed

    Bonneh-Barkay, Dafna; Langston, William J; Di Monte, Donato A

    2005-01-01

    A loss of nigrostriatal dopaminergic neurons is the primary neurodegenerative feature of Parkinson's disease. Paraquat, a known redox cycling herbicide, has recently been shown to kill selectively nigrostriatal dopaminergic cells in the mouse model. The purpose of this study was to test the ability of paraquat and other redox cycling pesticides to damage dopaminergic neurons in primary mesencephalic cultures. Addition of paraquat, diquat, or benzyl viologen to mesencephalic cultures induced morphological changes (e.g., dystrophic neuronal processes) consistent with dopaminergic cell injury. The three pesticides also caused cell death as assessed by a reduction of the number of tyrosine hydroxylase-immunoreactive neurons and a dose-dependent decrease in [(3)H]dopamine uptake. Quite interestingly, diquat and benzyl viologen were significantly more toxic than paraquat, probably reflecting their more pronounced ability to trigger redox cycling reactions. The data support a role of redox cycling as a mechanism of dopaminergic cell degeneration and suggest that the property of redox cycling should be taken into consideration when evaluating putative environmental risk factors for Parkinson's disease.

  9. Zinc Modulates Nanosilver-Induced Toxicity in Primary Neuronal Cultures.

    PubMed

    Ziemińska, Elżbieta; Strużyńska, Lidia

    2016-02-01

    Silver nanoparticles (NAg) have recently become one of the most commonly used nanomaterials. Since the ability of nanosilver to enter the brain has been confirmed, there has been a need to investigate mechanisms of its neurotoxicity. We previously showed that primary neuronal cultures treated with nanosilver undergo destabilization of calcium homeostasis via a mechanism involving glutamatergic NMDA receptors. Considering the fact that zinc interacts with these receptors, the aim of the present study was to examine the role of zinc in mechanisms of neuronal cell death in primary cultures. In cells treated with nanosilver, we noted an imbalance between extracellular and intracellular zinc levels. Thus, the influence of zinc deficiency and supplementation on nanosilver-evoked cytotoxicity was investigated by treatment with TPEN (a chelator of zinc ions), or ZnCl(2), respectively. Elimination of zinc leads to complete death of nanosilver-treated CGCs. In contrast, supplementation with ZnCl(2) increases viability of CGCs in a dose-dependent manner. Addition of zinc provided protection against the extra/intracellular calcium imbalance in a manner similar to MK-801, an antagonist of NMDA receptors. Zinc chelation by TPEN decreases the mitochondrial potential and dramatically increases the rate of production of reactive oxygen species. Our results indicate that zinc supplementation positively influences nanosilver-evoked changes in CGCs. This is presumed to be due to an inhibitory effect on NMDA-sensitive calcium channels.

  10. A reporter assay for target validation in primary neuronal cultures.

    PubMed

    Pollio, G; Roncarati, R; Seredenina, T; Terstappen, G C; Caricasole, A

    2008-07-15

    The deposition of beta-amyloid peptides (Abeta42 and Abeta40) in neuritic plaques is one of the hallmarks of Alzheimer's disease (AD), and genes modulating their brain levels and neuronal effects could result in future disease modifying therapies. The causal association of candidate targets with AD is of paramount importance in current drug discovery, as a lack of efficacy of many candidate drugs is often due to inadequate validation of their pharmacological target. In Alzheimer's as well as in other neurodegenerative diseases, in vitro target validation is hampered by the difficulty of transfecting primary neuronal cultures and assaying the effects of genes on neuronal viability. Here we describe a rapid, sensitive and simple reporter-based assay for the validation of genes putatively associated with Abeta-mediated neurotoxicity, which can in principle be extended to the validation of targets in the context of other neuronal insults. The assay is suitable for the generation of robust and reproducible data in primary neuronal cultures allowing the dissection at a molecular level of complex pathways activated by the toxic insult in a cellular context that more closely represents the real disease situation.

  11. Hemispheric asymmetry in cerebrovascular reactivity of the human primary motor cortex: an in vivo study at 7 T.

    PubMed

    Driver, Ian D; Andoh, Jamila; Blockley, Nicholas P; Francis, Susan T; Gowland, Penny A; Paus, Tomáš

    2015-05-01

    Current functional MRI (fMRI) approaches assess underlying neuronal activity through monitoring the related local variations in cerebral blood oxygenation, blood volume and blood flow. This vascular response is likely to vary across brain regions and across individuals, depending on the composition of the local vascular bed and on the vascular capacity to dilate. The most widely used technique uses the blood oxygen level dependent (BOLD) fMRI signal, which arises from a complex combination of all of these factors. The model of handedness provides a case where one brain region (dominant motor cortex) is known to have a stronger BOLD response over another (non-dominant motor cortex) during hand motor task performance. We predict that this is accompanied by a higher vascular reactivity in the dominant motor cortex, when compared with the non-dominant motor cortex. Precise measurement of end-tidal CO2 and a novel sinusoidal CO2 respiratory challenge were combined with the high sensitivity and finer spatial resolution available for fMRI at 7 T to measure BOLD cerebrovascular reactivity (CVR) in eight healthy male participants. BOLD CVR was compared between the left (dominant) and right (non-dominant) primary motor cortices of right-handed adults. Hemispheric asymmetry in vascular reactivity was predicted and observed in the primary motor cortex (left CVR = 0.60 ± 0.15%/mm Hg; right CVR = 0.47 ± 0.08%/mm Hg; left CVR > right CVR, P = 0.04), the first reported evidence of such a vascular difference. These findings demonstrate a cerebral vascular asymmetry between the left and right primary motor cortex. The origin of this asymmetry largely arises from the contribution of large draining veins. This work has implications for future motor laterality studies that use BOLD, and it is also suggestive of a vascular plasticity in the human primary motor cortex.

  12. Aspergillus fumigatus biofilm on primary human sinonasal epithelial culture.

    PubMed

    Singhal, Deepti; Baker, Leonie; Wormald, Peter-John; Tan, Lorwai

    2011-01-01

    Bacterial biofilms have been implicated in chronic rhinosinusitis (CRS). However, direct evidence in support of fungal biofilms in sinus disease is lacking in the literature. This study was designed to develop and characterize an in vitro Aspergillus fumigatus biofilm model on primary human sinonasal epithelial cell culture. Sinonasal biopsy specimens harvested during endoscopic sinus surgery of six CRS patients and three pituitary tumor (control) patients were cultured in Dulbecco's modified Eagle media (DMEM; Invitrogen)/Hams F12 airway media to encourage epithelial cell proliferation. Epithelial cells separated by immunomagnetic beads were seeded in tissue culture-treated Y-shaped microslides. At confluence the primary cultures were inoculated with A. fumigatus spores. Fungus was allowed to germinate and form biofilms under two in vitro conditions: (1) static (no flow through of media) and (2) continuous flow coculture (continuous flow movement of media). At regular intervals cocultures were stained with FUN-1, concanavalin A-alexa fluor 488, and examined by confocal scanning laser microscopy. Comstat software was used to assess biomass and thickness. A. fumigatus formed three-dimensional biofilm structures with parallel-packed, cross-linked hyphae and channels/passages. Metabolically active hyphae showed orange-red fluorescing intravacuolar structures. Extracellular matrix (ECM) between/around the hyphae fluoresced intense green. A. fumigatus biofilms development occurred in five stages: (1) conidial attachment to epithelial cells, (2) hyphal proliferation, (3) ECM production, (4) hyphal parallel packing and cross-linking, and (5) channel/pores formation. Mature biofilms showed basal conidial, middle hyphal, and superficial ECM layers. Biofilms formed under flow conditions displayed more robust and faster growth kinetics when compared with that under static conditions, with a thick, stocky, wrinkly/undulating hyphal growth and extensive ECM production. The

  13. Accumulation of silver nanoparticles by cultured primary brain astrocytes.

    PubMed

    Luther, Eva M; Koehler, Yvonne; Diendorf, Joerg; Epple, Matthias; Dringen, Ralf

    2011-09-16

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO(3) already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  14. Accumulation of silver nanoparticles by cultured primary brain astrocytes

    NASA Astrophysics Data System (ADS)

    Luther, Eva M.; Koehler, Yvonne; Diendorf, Joerg; Epple, Matthias; Dringen, Ralf

    2011-09-01

    Silver nanoparticles (AgNP) are components of various food industry products and are frequently used for medical equipment and materials. Although such particles enter the vertebrate brain, little is known on their biocompatibility for brain cells. To study the consequences of an AgNP exposure of brain cells we have treated astrocyte-rich primary cultures with polyvinylpyrrolidone (PVP)-coated AgNP. The incubation of cultured astrocytes with micromolar concentrations of AgNP for up to 24 h resulted in a time- and concentration-dependent accumulation of silver, but did not compromise the cell viability nor lower the cellular glutathione content. In contrast, the incubation of astrocytes for 4 h with identical amounts of silver as AgNO3 already severely compromised the cell viability and completely deprived the cells of glutathione. The accumulation of AgNP by astrocytes was proportional to the concentration of AgNP applied and significantly lowered by about 30% in the presence of the endocytosis inhibitors chloroquine or amiloride. Incubation at 4 °C reduced the accumulation of AgNP by 80% compared to the values obtained for cells that had been exposed to AgNP at 37 °C. These data demonstrate that viable cultured brain astrocytes efficiently accumulate PVP-coated AgNP in a temperature-dependent process that most likely involves endocytotic pathways.

  15. Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis.

    PubMed

    Costagli, M; Donatelli, G; Biagi, L; Caldarazzo Ienco, E; Siciliano, G; Tosetti, M; Cosottini, M

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1) in patients with upper motor neuron (UMN) impairment is pronouncedly hypointense in Magnetic Resonance (MR) T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution. MR raw data were used for Quantitative Susceptibility Mapping (QSM). Measures of magnetic susceptibility correlated with the expected concentration of non-heme iron in different regions of the cerebral cortex in healthy subjects. In ALS patients, significant increases in magnetic susceptibility co-localized with the T2* hypointensity observed in the middle and deep layers of M1. The magnetic susceptibility, hence iron concentration, of the deep cortical layers of patients' M1 subregions corresponding to Penfield's areas of the hand and foot in both hemispheres significantly correlated with the clinical scores of UMN impairment of the corresponding limbs. QSM therefore reflects the presence of iron deposits related to neuroinflammatory reaction and cortical microgliosis, and might prove useful in estimating M1 iron concentration, as a possible radiological sign of severe UMN burden in ALS patients.

  16. Motor Speech Phenotypes of Frontotemporal Dementia, Primary Progressive Aphasia, and Progressive Apraxia of Speech.

    PubMed

    Poole, Matthew L; Brodtmann, Amy; Darby, David; Vogel, Adam P

    2017-04-14

    Our purpose was to create a comprehensive review of speech impairment in frontotemporal dementia (FTD), primary progressive aphasia (PPA), and progressive apraxia of speech in order to identify the most effective measures for diagnosis and monitoring, and to elucidate associations between speech and neuroimaging. Speech and neuroimaging data described in studies of FTD and PPA were systematically reviewed. A meta-analysis was conducted for speech measures that were used consistently in multiple studies. The methods and nomenclature used to describe speech in these disorders varied between studies. Our meta-analysis identified 3 speech measures which differentiate variants or healthy control-group participants (e.g., nonfluent and logopenic variants of PPA from all other groups, behavioral-variant FTD from a control group). Deficits within the frontal-lobe speech networks are linked to motor speech profiles of the nonfluent variant of PPA and progressive apraxia of speech. Motor speech impairment is rarely reported in semantic and logopenic variants of PPA. Limited data are available on motor speech impairment in the behavioral variant of FTD. Our review identified several measures of speech which may assist with diagnosis and classification, and consolidated the brain-behavior associations relating to speech in FTD, PPA, and progressive apraxia of speech.

  17. Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke

    PubMed Central

    Li, Yongxin; Wang, Defeng; Zhang, Heye; Wang, Ya; Wu, Ping; Zhang, Hongwu; Yang, Yang; Huang, Wenhua

    2016-01-01

    Abstract The authors investigated the changes in connectivity networks of the bilateral primary motor cortex (M1) of subcortical stroke patients using a multimodal neuroimaging approach with antiplatelet therapy. Nineteen patients were scanned at 2 time points: before and 1 month after the treatment. The authors assessed the resting-state functional connectivity (FC) and probabilistic fiber tracking of left and right M1 of every patient, and then compared these results to the 15 healthy controls. The authors also evaluated the correlations between the neuroimaging results and clinical scores. Compared with the controls, the patients showed a significant decrease of FC in the contralateral motor cortex before treatment, and the disrupted FC was restored after treatment. The fiber tracking results in the controls indicated that the body of the corpus callosum should be the main pathway connecting the M1 and contralateral hemispheres. All patients exhibited reduced probability of structural connectivity within this pathway before treatment and which was restored after treatment. Significant correlations were also found in these patients between the connectivity results and clinical scores, which might imply that the connectivity of M1 can be used to evaluate the motor skills in stroke patients. These findings can help elucidate the neural mechanisms responsible for the brain connectivity recovery after stroke. PMID:26871777

  18. Probing changes in corticospinal excitability following theta burst stimulation of the human primary motor cortex.

    PubMed

    Goldsworthy, Mitchell R; Vallence, Ann-Maree; Hodyl, Nicolette A; Semmler, John G; Pitcher, Julia B; Ridding, Michael C

    2016-01-01

    To determine whether the intensity of transcranial magnetic stimulation (TMS) used to probe changes in corticospinal excitability influences the measured plasticity response to theta burst stimulation (TBS) of the human primary motor cortex. Motor evoked potential (MEP) input/output (I/O) curves were recorded before and following continuous TBS (cTBS) (Experiment 1; n=18) and intermittent TBS (iTBS) (Experiment 2; n=18). The magnitude and consistency of MEP depression induced by cTBS was greatest when probed using stimulus intensities at or above 150% of resting motor threshold (RMT). In contrast, facilitation of MEPs following iTBS was strongest and most consistent at 110% of RMT. The plasticity response to both cTBS and iTBS is influenced by the stimulus intensity used to probe the induced changes in corticospinal excitability. The results highlight the importance of the test stimulus intensity used to assess TBS-induced changes in corticospinal excitability when interpreting neuroplasticity data, and suggest that a number of test intensities may be required to reliably probe the plasticity response. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Supplementary motor area and primary auditory cortex activation in an expert break-dancer during the kinesthetic motor imagery of dance to music.

    PubMed

    Olshansky, Michael P; Bar, Rachel J; Fogarty, Mary; DeSouza, Joseph F X

    2015-01-01

    The current study used functional magnetic resonance imaging to examine the neural activity of an expert dancer with 35 years of break-dancing experience during the kinesthetic motor imagery (KMI) of dance accompanied by highly familiar and unfamiliar music. The goal of this study was to examine the effect of musical familiarity on neural activity underlying KMI within a highly experienced dancer. In order to investigate this in both primary sensory and motor planning cortical areas, we examined the effects of music familiarity on the primary auditory cortex [Heschl's gyrus (HG)] and the supplementary motor area (SMA). Our findings reveal reduced HG activity and greater SMA activity during imagined dance to familiar music compared to unfamiliar music. We propose that one's internal representations of dance moves are influenced by auditory stimuli and may be specific to a dance style and the music accompanying it.

  20. Optimal 3-D culture of primary articular chondrocytes for use in the Rotating Wall Vessel Bioreactor

    PubMed Central

    Mellor, Liliana F.; Baker, Travis L.; Brown, Raquel J.; Catlin, Lindsey W.; Oxford, Julia Thom

    2014-01-01

    INTRODUCTION Reliable culturing methods for primary articular chondrocytes are essential to study the effects of loading and unloading on joint tissue at the cellular level. Due to the limited proliferation capacity of primary chondrocytes and their tendency to dedifferentiate in conventional culture conditions, long-term culturing conditions of primary chondrocytes can be challenging. The goal of this study was to develop a suspension culturing technique that not only would retain the cellular morphology but also maintain gene expression characteristics of primary articular chondrocytes. METHODS Three-dimensional culturing methods were compared and optimized for primary articular chondrocytes in the rotating wall vessel bioreactor, which changes the mechanical culture conditions to provide a form of suspension culture optimized for low shear and turbulence. We performed gene expression analysis and morphological characterization of cells cultured in alginate beads, Cytopore-2 microcarriers, primary monolayer culture, and passaged monolayer cultures using reverse transcription-PCR and laser scanning confocal microscopy. RESULTS Primary chondrocytes grown on Cytopore-2 microcarriers maintained the phenotypical morphology and gene expression pattern observed in primary bovine articular chondrocytes, and retained these characteristics for up to 9 days. DISCUSSION Our results provide a novel and alternative culturing technique for primary chondrocytes suitable for studies that require suspension such as those using the rotating wall vessel bioreactor. In addition, we provide an alternative culturing technique for primary chondrocytes that can impact future mechanistic studies of osteoarthritis progression, treatments for cartilage damage and repair, and cartilage tissue engineering. PMID:25199120

  1. Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

    PubMed Central

    2010-01-01

    Background Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited. Results By investigating the positioning of all human chromosomes in primary fibroblasts that have left the proliferative cell cycle, we have demonstrated that in cells made quiescent by reversible growth arrest, chromosome positioning is altered considerably. We found that with the removal of serum from the culture medium, chromosome repositioning took less than 15 minutes, required energy and was inhibited by drugs affecting the polymerization of myosin and actin. We also observed that when cells became quiescent, the nuclear distribution of nuclear myosin 1β was dramatically different from that in proliferating cells. If we suppressed the expression of nuclear myosin 1β by using RNA-interference procedures, the movement of chromosomes after 15 minutes in low serum was inhibited. When high serum was restored to the serum-starved cultures, chromosome repositioning was evident only after 24 to 36 hours, and this coincided with a return to a proliferating distribution of nuclear myosin 1β. Conclusions These findings demonstrate that genome organization in interphase nuclei is altered considerably when cells leave the proliferative cell cycle and that repositioning of chromosomes relies on efficient functioning of an active nuclear motor complex that contains nuclear myosin 1β. PMID:20070886

  2. Primary Motor Cortex Excitability in Karate Athletes: A Transcranial Magnetic Stimulation Study.

    PubMed

    Monda, Vincenzo; Valenzano, Anna; Moscatelli, Fiorenzo; Salerno, Monica; Sessa, Francesco; Triggiani, Antonio I; Viggiano, Andrea; Capranica, Laura; Marsala, Gabriella; De Luca, Vincenzo; Cipolloni, Luigi; Ruberto, Maria; Precenzano, Francesco; Carotenuto, Marco; Zammit, Christian; Gelzo, Monica; Monda, Marcellino; Cibelli, Giuseppe; Messina, Giovanni; Messina, Antonietta

    2017-01-01

    Purpose: The mechanisms involved in the coordination of muscle activity are not completely known: to investigate adaptive changes in human motor cortex Transcranial magnetic stimulation (TMS) was often used. The sport models are frequently used to study how the training may affect the corticospinal system excitability: Karate represents a valuable sport model for this kind of investigations for its high levels of coordination required to athletes. This study was aimed at examining possible changes in the resting motor threshold (rMT) and in the corticospinal response in karate athletes, and at determining whether athletes are characterized by a specific value of rMT. Methods: We recruited 25 right-handed young karate athletes and 25 matched non-athletes. TMS was applied to primary motor cortex (M1). Motor evoked potential (MEP) were recorded by two electrodes placed above the first dorsal interosseous (FDI) muscle. We considered MEP latencies and amplitudes at rMT, 110% of rMT, and 120% of rMT. Results: The two groups were similar for age (p > 0.05), height (p > 0.05) and body mass (p > 0.05). The TMS had a 70-mm figure-of-eight coil and a maximum output of 2.2 T, placed over the left motor cortex. During the stimulation, a mechanical arm kept the coil tangential to the scalp, with the handle at 45° respect to the midline. The SofTaxic navigator system (E.M.S. Italy, www.emsmedical.net) was used in order to correctly identifying and repeating the stimulation for every subject. Compared to non-athletes, athletes showed a lower resting motor threshold (p < 0.001). Furthermore, athletes had a lower MEP latency (p < 0.001) and a higher MEP amplitude (p < 0.001) compared to non-athletes. Moreover, a ROC curve for rMT was found significant (area: 0.907; sensitivity 84%, specificity 76%). Conclusions: As the main finding, the present study showed significant differences in cortical excitability between athletes and non-athletes. The training can improve cortical

  3. The Effect of Visual and Auditory Enhancements on Excitability of the Primary Motor Cortex during Motor Imagery: A Pilot Study

    ERIC Educational Resources Information Center

    Ikeda, Kohei; Higashi, Toshio; Sugawara, Kenichi; Tomori, Kounosuke; Kinoshita, Hiroshi; Kasai, Tatsuya

    2012-01-01

    The effect of visual and auditory enhancements of finger movement on corticospinal excitability during motor imagery (MI) was investigated using the transcranial magnetic stimulation technique. Motor-evoked potentials were elicited from the abductor digit minimi muscle during MI with auditory, visual and, auditory and visual information, and no…

  4. The Effect of Visual and Auditory Enhancements on Excitability of the Primary Motor Cortex during Motor Imagery: A Pilot Study

    ERIC Educational Resources Information Center

    Ikeda, Kohei; Higashi, Toshio; Sugawara, Kenichi; Tomori, Kounosuke; Kinoshita, Hiroshi; Kasai, Tatsuya

    2012-01-01

    The effect of visual and auditory enhancements of finger movement on corticospinal excitability during motor imagery (MI) was investigated using the transcranial magnetic stimulation technique. Motor-evoked potentials were elicited from the abductor digit minimi muscle during MI with auditory, visual and, auditory and visual information, and no…

  5. Epidural motor cortex stimulation suppresses somatosensory evoked potentials in the primary somatosensory cortex of the rat.

    PubMed

    Chiou, Ruei-Jen; Lee, Hsiao-Yun; Chang, Chen-Wei; Lin, Kuan-Hung; Kuo, Chung-Chih

    2012-06-29

    Motor cortex stimulation (MCS) is a promising clinical procedure to help alleviate chronic pain. Animal models demonstrated that MCS is effective in lessening nocifensive behaviors. The present study explored the effects of MCS on cortical somatosensory evoked potentials (SEPs) recorded at the primary somatosensory cortex (SI) of the rat. SEPs were evoked by electrical stimulation applied to the contralateral forepaws. Effects of different intensities, frequencies, and durations of MCS were tested. MCS at ≥2V suppressed SEPs of the ipsilateral SI. Suppression lasted 120 min at an intensity of 5 V. The optimal frequency was 50 Hz, and the duration was 30s. In contrast, MCS did not affect SEPs recorded on the contralateral SI. Cortical stimulation out of the motor cortex did not induce a decrease in the ipsilateral SEPs. We also investigated involvement of the endogenous opioid system in this inhibition of SEPs induced by MCS. The opioid antagonist, naloxone (0.5 mg/kg), was administered 30 min before MCS. Application of naloxone completely prevented the inhibitory effect of MCS on ipsilateral SEPs. These results demonstrate that MCS blocked the transmission of somatosensory information to the primary somatosensory cortex, and this interference was mediated by the endogenous opioid system. This inhibitory effect on sensory transmission induced by MCS may reflect its antinociceptive effect.

  6. Automatic detection and quantitative analysis of cells in the mouse primary motor cortex

    NASA Astrophysics Data System (ADS)

    Meng, Yunlong; He, Yong; Wu, Jingpeng; Chen, Shangbin; Li, Anan; Gong, Hui

    2014-09-01

    Neuronal cells play very important role on metabolism regulation and mechanism control, so cell number is a fundamental determinant of brain function. Combined suitable cell-labeling approaches with recently proposed three-dimensional optical imaging techniques, whole mouse brain coronal sections can be acquired with 1-μm voxel resolution. We have developed a completely automatic pipeline to perform cell centroids detection, and provided three-dimensional quantitative information of cells in the primary motor cortex of C57BL/6 mouse. It involves four principal steps: i) preprocessing; ii) image binarization; iii) cell centroids extraction and contour segmentation; iv) laminar density estimation. Investigations on the presented method reveal promising detection accuracy in terms of recall and precision, with average recall rate 92.1% and average precision rate 86.2%. We also analyze laminar density distribution of cells from pial surface to corpus callosum from the output vectorizations of detected cell centroids in mouse primary motor cortex, and find significant cellular density distribution variations in different layers. This automatic cell centroids detection approach will be beneficial for fast cell-counting and accurate density estimation, as time-consuming and error-prone manual identification is avoided.

  7. Multimodal assessment of primary motor cortex integrity following sport concussion in asymptomatic athletes

    PubMed Central

    Tremblay, Sara; Beaulé, Vincent; Proulx, Sébastien; Tremblay, Sébastien; Marjańska, Małgorzata; Doyon, Julien; Lassonde, Maryse; Théoret, Hugo

    2015-01-01

    Objective Recent studies have shown, in asymptomatic concussed athletes, metabolic disruption in the primary motor cortex (M1) and abnormal intracortical inhibition lasting for more than six months. The present study aims to assess if these neurochemical and neurophysiological alterations are persistent and linked to M1 cortical thickness. Methods Sixteen active football players who sustained their last concussion, on average, three years prior to testing and 14 active football players who never sustained a concussion were recruited for a single session of proton magnetic resonance spectroscopy (1H-MRS) and transcranial magnetic stimulation (TMS). Measures of M1 and whole brain cortical thickness were acquired, and 1H-MRS data were acquired from left M1 using a MEGA-PRESS sequence. Cortical silent period (CSP) and long-interval intracortical inhibition (LICI) were measured with TMS applied over left M1. Results No significant group differences were observed for metabolic concentrations, TMS measures, and cortical thickness. However, whereas GABA and glutamate levels, and GABA levels and M1 mean thickness were positively correlated in control athletes, these relationships were absent in concussed athletes. Conclusion These data suggest the general absence of neurophysiologic, neurometabolic and neuroanatomical disruptions in M1 three years following the last concussive event. However, correlational analyses suggest the presence of a slight metabolic imbalance between GABA and glutamate concentrations in the primary motor cortex of concussed athletes. Significance The present study highlights the importance of multimodal assesments of the impacts of sport concussions. PMID:24462505

  8. (-) deprenyl attenuates aluminium induced neurotoxicity in primary cortical cultures.

    PubMed

    Munirathinam, S; Lakshmana, M K; Raju, T R

    1996-06-01

    The role of (-) deprenyl in offering neuroprotection to cortical neurons exposed to Aluminium chloride (AlCl3) was examined. Primary cortical cultures derived from newborn rats were exposed to AlCl3 on 6th day in vitro, at 100,200,400,600,800 and 1000 microM concentrations of AlCl3. After 48 h of AlCl3 exposure, many nerve cell bodies were swollen; a beading of neurites and a disruption of the neuritic network were also observed suggesting neurodegeneration. Lactate dehydrogenase (LDH) efflux increased in a dose-dependent manner (59-120%). (-) Deprenyl co-exposure at concentrations of 10(-7), 10(-8) and 10(-9) M significantly attenuated both the morphological alterations and the LDH efflux induced by AlCl3. This in vitro study has demonstrated that (-) deprenyl can protect neurons from aluminium induced neurotoxicity.

  9. Assessment of cell viability in primary neuronal cultures.

    PubMed

    Aras, Mandar A; Hartnett, Karen A; Aizenman, Elias

    2008-07-01

    This unit contains five protocols for assaying cell viability in vitro using primary neuronal cultures, including a novel method for use with transfected neurons. Three of the assays are based on the principle that cell death cascades alter membrane permeability. The lactate dehydrogenase (LDH) release assay measures the amount of the cytoplasmic enzyme released into the bathing medium, while the trypan blue and propidium iodide assays measure the ability of cells to exclude dye from their cytoplasm. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay measures the mitochondrial activity of viable cells by quantifying the conversion of the tetrazolium salt to its formazan product. Finally, the fifth assay details the measurement of luciferase expression as an indication of neuronal viability within a relatively small population of transfected neurons.

  10. Healthcare professionals' accounts of challenges in managing motor neurone disease in primary healthcare: a qualitative study.

    PubMed

    Lerum, Sverre Vigeland; Solbraekke, Kari Nyheim; Frich, Jan C

    2017-02-22

    Motor neurone disease (MND) is a progressive neurological disease causing muscle wasting, gradual paralysis and respiratory failure, with a life expectancy of 2-4 years. In order to better understand how MND is managed in the community, we conducted a qualitative study to explore the challenges healthcare professionals encounter when managing MND in primary healthcare. Based on data from 15 semi-structured interviews with primary healthcare professionals in Norway, we found that MND is viewed as a condition that requires exceptional effort and detailed planning. Healthcare professionals reported five main challenges in managing MND in primary healthcare: (i) building relationships with those giving and receiving care in the home; (ii) preventing caregiver burnout and breakdown; (iii) providing tailored care; (iv) ensuring good working conditions in patients' homes; and (v) recruiting and retaining qualified nursing assistants. Healthcare professionals reported needing working conditions that allow them to tailor their approach to the personal, emotional and existential nature of care preferences of those living with MND. However, people with MND and their families were sometimes perceived by healthcare professionals to prefer a strictly task-focused relationship with care providers. Such relationships limited the healthcare professionals' control over the MND trajectory and their capacity to prevent family caregiver burnout and breakdown. Adequate resources, along with training and support of nursing assistants, may increase the continuity of nursing assistants. Responsiveness to patient and family needs may enhance collaboration and promote tailored primary care and support for patients with MND and their families.

  11. Regulation of human renin expression in chorion cell primary cultures

    SciTech Connect

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L. )

    1990-10-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3{endash} to 6{endash}fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'{endash}flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'{endash}flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter.

  12. ATP stimulates calcium influx in primary astrocyte cultures

    SciTech Connect

    Neary, J.T.; van Breemen, C.; Forster, E.; Norenberg, L.O.; Norenberg, M.D.

    1988-12-30

    The effect of ATP and other purines on /sup 45/Ca uptake was studied in primary cultures of rat astrocytes. Treatment of the cells with ATP for 1 to 30 min brought about an increase in cellular /sup 45/Ca. Stimulation of calcium influx by ATP was investigated using a 90 sec exposure to /sup 45/Ca and over a concentration range of 0.1 nM to 3 mM; a biphasic dose-response curve was obtained with EC50 values of 0.3 nM and 9 uM, indicating the presence of low and high affinity purinergic binding sites. Similar levels of /sup 45/Ca influx at 90 sec were observed with ATP, ADP and adenosine (all at 100 uM). Prior treatment of the cultures with LaCl3 blocked the purine-induced /sup 45/Ca influx. These findings indicate that one pathway for calcium entry in astrocytes involves purinergic receptor-operated, calcium channels.

  13. Political, cultural and economic foundations of primary care in Europe.

    PubMed

    Kringos, Dionne S; Boerma, Wienke G W; van der Zee, Jouke; Groenewegen, Peter P

    2013-12-01

    This article explores various contributing factors to explain differences in the strength of the primary care (PC) structure and services delivery across Europe. Data on the strength of primary care in 31 European countries in 2009/10 were used. The results showed that the national political agenda, economy, prevailing values, and type of healthcare system are all important factors that influence the development of strong PC. Wealthier countries are associated with a weaker PC structure and lower PC accessibility, while Eastern European countries seemed to have used their growth in national income to strengthen the accessibility and continuity of PC. Countries governed by left-wing governments are associated with a stronger PC structure, accessibility and coordination of PC. Countries with a social-security based system are associated with a lower accessibility and continuity of PC; the opposite is true for transitional systems. Cultural values seemed to affect all aspects of PC. It can be concluded that strengthening PC means mobilising multiple leverage points, policy options, and political will in line with prevailing values in a country.

  14. Properties of primary motor cortical local field potentials in the leg and trunk representations during arm movements.

    PubMed

    Tobaa, Adil A; Best, Matthew D; Balasubramanian, Karthikeyan; Takahashi, Kazutaka; Hatsopoulos, Nicholas G

    2016-08-01

    Large, spatially-distributed populations of motor cortical neurons are recruited during upper limb movements. Here, we examined how beta attenuation, a mesoscopic reflection of unit engagement, varies across a spatially expansive sampling of primary motor cortex in a non-human primate (macaca mulatta). We found that electrodes in both the trunk and leg representation of motor cortex exhibit qualitatively similar behavior to electrodes in the arm representation during a planar reaching task, despite the fact that there were no overt movements of the trunk or leg. These findings are interpreted in the context of a state-based brain machine interface.

  15. Observing back pain provoking lifting actions modulates corticomotor excitability of the observer's primary motor cortex.

    PubMed

    Lehner, Rea; Meesen, Raf; Wenderoth, Nicole

    2017-07-01

    Observing another person experiencing exogenously inflicted pain (e.g. by a sharp object penetrating a finger) modulates the excitability of the observer' primary motor cortex (M1). By contrast, far less is known about the response to endogenously evoked pain such as sudden back pain provoked by lifting a heavy object. Here, participants (n=26) observed the lifting of a heavy object. During this action the actor (1) flexed and extended the legs (LEG), (2) flexed and extended the back (BACK) or (3) flexed and extended the back which caused visible pain (BACKPAIN). Corticomotor excitability was measured by applying a single transcranial magnetic stimulation pulse to the M1 representation of the muscle erector spinae and participants scored their perception of the actor's pain on the numeric pain rating scale (NPRS). The participants scored vicarious pain as highest during the BACKPAIN condition and lowest during the LEG condition. MEP size was significantly lower for the LEG than the BACK and BACKPAIN condition. Although we found no statistical difference in the motor-evoked potential (MEP) size between the conditions BACK and BACKPAIN, there was a significant correlation between the difference in NPRS scores between the conditions BACKPAIN and BACK and the difference in MEP size between these conditions. Participants who believed the vicarious pain to be much stronger in the BACKPAIN than in the BACK condition also exhibited higher MEPs for the BACKPAIN than the BACK condition. Our results indicate that observing how others lift heavy objects facilitates motor representations of back muscles in the observer. Modulation occurs in a movement-specific manner and is additionally modulated by the extent to which the participants perceived the actor's pain. Our findings suggest that movement observation might be a promising paradigm to study the brain's response to back pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Interhemispheric interaction between human dorsal premotor and contralateral primary motor cortex.

    PubMed

    Mochizuki, Hitoshi; Huang, Ying-Zu; Rothwell, John C

    2004-11-15

    We used transcranial magnetic stimulation (TMS) in a paired pulse protocol to investigate interhemispheric interactions between the right dorsal premotor (dPM) and left primary motor cortex (M1) using interstimulus intervals of 4, 6, 8, 10, 12, 16 and 20 ms in ten healthy subjects. A conditioning stimulus over right dPM at an intensity of either 90 or 110% resting motor threshold (RMT) suppressed motor-evoked potentials (MEPs) evoked in the first dorsal interosseous (FDI) muscle by stimulation of left M1. Maximum effects occurred for interstimulus intervals (ISIs) of 8-10 ms. There was no effect if the conditioning stimulus was applied 2.5 cm lateral, anterior or medial to dPM. The effect differed from previously described M1 interhemispheric inhibition in that the threshold for the latter was greater than 90% RMT, whereas stimulation of the dPM at the same intensity led to significant inhibition. In addition, voluntary contraction of the left FDI (i.e. contralateral to the conditioning TMS) enhanced interhemispheric inhibition from right M1 but had no effect on the inhibition from right dPM. Finally, conditioning to right dPM at 90% RMT reduced short-interval intracortical inhibition (SICI; at ISI = 2 ms) in left M1 whilst there was no effect if the conditioning stimulus was applied to right M1. We conclude that conditioning TMS over dPM has effects that differ from the previous pattern of interhemispheric inhibition described between bilateral M1s. This may reflect the existence of commissural fibres between dPM and contralateral M1 that may play a role in bimanual coordination.

  17. Interhemispheric inhibition in distal and proximal arm representations in the primary motor cortex.

    PubMed

    Harris-Love, Michelle L; Perez, Monica A; Chen, Robert; Cohen, Leonardo G

    2007-03-01

    Interhemispheric inhibitory interactions (IHI) operate between homologous distal hand representations in primary motor cortex (M1). It is not known whether proximal arm representations exhibit comparable effects on their homologous counterparts. We studied IHI in different arm representations, targeting triceps brachii (TB, n = 13), first dorsal interosseous (FDI, n = 13), and biceps brachii (BB, n = 7) muscles in healthy volunteers. Transcranial magnetic stimulation test stimuli (TS) were delivered to M1 contralateral to the target muscle preceded 10 ms by a conditioning stimulus (CS) to the opposite M1 at 110-150% resting motor threshold (RMT). IHI was calculated as the ratio between motor-evoked potential (MEP) amplitudes in conditioned relative to unconditioned trials. Mean RMTs were 38.9, 46.9, and 46.0% of stimulator output in FDI, TB, and BB muscles, respectively. IHI was 0.45 +/- 0.41 (FDI), 0.78 +/- 0.38 (TB), and 0.52 +/- 0.32 (BB, P < 0.01) when test MEP amplitudes were matched and 0.28 +/- 0.17 (FDI) and 0.85 +/- 0.31 (TB, P < 0.05) when TS intensities expressed as percentage RMT were matched. Significant IHI (P < 0.05) was identified with minimal CS intensities (expressed as percentage stimulator output) in the 30 s for FDI, 60 s for TB, and 40 s for BB. Additionally, a CS of roughly 120% RMT suppressed the test MEP but not a test H-reflex in BB, suggesting IHI observed in BB is likely mediated by a supraspinal mechanism. We conclude that IHI differs between different arm muscle representations, comparable between BB and FDI but lesser for TB. This finding suggests the amount of IHI between different arm representations does not strictly follow a proximal-to-distal gradient, but may be related to the role of each muscle in functional movement synergies.

  18. Bilateral tDCS on Primary Motor Cortex: Effects on Fast Arm Reaching Tasks

    PubMed Central

    Arias, Pablo; Corral-Bergantiños, Yoanna; Robles-García, Verónica; Madrid, Antonio; Oliviero, Antonio; Cudeiro, Javier

    2016-01-01

    Background The effects produced by transcranial direct current stimulation (tDCS) applied to the motor system have been widely studied in the past, chiefly focused on primary motor cortex (M1) excitability. However, the effects on functional tasks are less well documented. Objective This study aims to evaluate the effect of tDCS-M1 on goal-oriented actions (i.e., arm-reaching movements; ARM), in a reaction-time protocol. Methods 13 healthy subjects executed dominant ARM as fast as possible to one of two targets in front of them while surface EMG was recorded. Participants performed three different sessions. In each session they first executed ARM (Pre), then received tDCS, and finally executed Post, similar to Pre. Subjects received three different types of tDCS, one per session: In one session the anode was on right-M1 (AR), and the cathode on the left-M1 (CL), thus termed AR-CL; AL-CR reversed the montage; and Sham session was applied likewise. Real stimulation was 1mA-10min while subjects at rest. Three different variables and their coefficients of variation (CV) were analyzed: Premotor times (PMT), reaction-times (RT) and movement-times (MT). Results triceps-PMT were significantly increased at Post-Sham, suggesting fatigue. Results obtained with real tDCS were not different depending on the montage used, in both cases PMT were significantly reduced in all recorded muscles. RT and MT did not change for real or sham stimulation. RT-CV and PMT-CV were reduced after all stimulation protocols. Conclusion tDCS reduces premotor time and fatigability during the execution of fast motor tasks. Possible underlying mechanisms are discussed. PMID:27490752

  19. Primary Cultures of Glomerular Parietal Epithelial Cells or Podocytes with Proven Origin

    PubMed Central

    Schulte, Kevin; Sechi, Antonio; Sauer-Lehnen, Sibille; Tag, Carmen; Boor, Peter; Kuppe, Christoph; Warsow, Gregor; Schordan, Sandra; Mostertz, Jörg; Chilukoti, Ravi Kumar; Homuth, Georg; Endlich, Nicole; Tacke, Frank; Weiskirchen, Ralf; Fuellen, Georg; Endlich, Karlhans; Floege, Jürgen; Smeets, Bart; Moeller, Marcus J.

    2012-01-01

    Parietal epithelial cells (PECs) are crucially involved in the pathogenesis of rapidly progressive glomerulonephritis (RPGN) as well as in focal and segmental glomerulosclerosis (FSGS). In this study, transgenic mouse lines were used to isolate pure, genetically tagged primary cultures of PECs or podocytes using FACsorting. By this approach, the morphology of primary glomerular epithelial cells in culture could be resolved: Primary podocytes formed either large cells with intracytoplasmatic extensions or smaller spindle shaped cells, depending on specific culture conditions. Primary PECs were small and exhibited a spindle-shaped or polygonal morphology. In the very early phases of primary culture, rapid changes in gene expression (e.g. of WT-1 and Pax-2) were observed. However, after prolonged culture primary PECs and podocytes still segregated clearly in a transcriptome analysis - demonstrating that the origin of primary cell cultures is important. Of the classical markers, synaptopodin and podoplanin expression were differentially regulated the most in primary PEC and podocyte cultures. However, no expression of any endogenous gene allowed to differentiate between the two cell types in culture. Finally, we show that the transcription factor WT1 is also expressed by PECs. In summary, genetic tagging of PECs and podocytes is a novel and necessary tool to derive pure primary cultures with proven origin. These cultures will be a powerful tool for the emerging field of parietal epithelial cell biology. PMID:22529955

  20. Dissociation of supplementary motor area and primary motor cortex in human subjects when comparing index and little finger movements with functional magnetic resonance imaging.

    PubMed

    Erdler, M; Windischberger, C; Lanzenberger, R; Edward, V; Gartus, A; Deecke, L; Beisteiner, R

    2001-11-02

    This study provides the first investigation of supplementary motor area (SMA) and primary motor cortex (MI) activation with similar movements differing only in subjective difficulty of motor control. Brain activation with simple tapping of the right index finger (well trained during daily life and easy to perform) was compared with tapping of the little finger (less trained and difficult to perform) using functional magnetic resonance imaging at 3 Tesla. Due to optimised movement standardisation, extrinsic influences on activation levels such as movement complexity, amplitude and frequency were minimised. Fifth finger tapping significantly increased the number of activated SMA voxels by 450% whereas MI activation showed no significant difference between fingers. We conclude that with similar movements the degree of subjective difficulty specifically modifies SMA but not MI activation.

  1. Antibody-Conjugated Single Quantum Dot Tracking of Membrane Neurotransmitter Transporters in Primary Neuronal Cultures.

    PubMed

    Bailey, Danielle M; Kovtun, Oleg; Rosenthal, Sandra J

    2017-01-01

    Single particle tracking (SPT) experiments have provided the scientific community with invaluable single-molecule information about the dynamic regulation of individual receptors, transporters, kinases, lipids, and molecular motors. SPT is an alternative to ensemble averaging approaches, where heterogeneous modes of motion might be lost. Quantum dots (QDs) are excellent probes for SPT experiments due to their photostability, high brightness, and size-dependent, narrow emission spectra. In a typical QD-based SPT experiment, QDs are bound to the target of interest and imaged for seconds to minutes via fluorescence video microscopy. Single QD spots in individual frames are then linked to form trajectories that are analyzed to determine their mean square displacement, diffusion coefficient, confinement index, and instantaneous velocity. This chapter describes a generalizable protocol for the single particle tracking of membrane neurotransmitter transporters on cell membranes with either unmodified extracellular antibody probes and secondary antibody-conjugated quantum dots or biotinylated extracellular antibody probes and streptavidin-conjugated quantum dots in primary neuronal cultures. The neuronal cell culture, the biotinylation protocol and the quantum dot labeling procedures, as well as basic data analysis are discussed.

  2. Ventral premotor to primary motor cortical interactions during noxious and naturalistic action observation.

    PubMed

    Lago, Angel; Koch, Giacomo; Cheeran, Binith; Márquez, Gonzalo; Sánchez, Jose Andrés; Ezquerro, Milagros; Giraldez, Manolo; Fernández-del-Olmo, Miguel

    2010-05-01

    Within the motor system, cortical areas such as the primary motor cortex (M1) and the ventral premotor cortex (PMv), are thought to be activated during the observation of actions performed by others. However, it is not known how the connections between these areas become active during action observation or whether these connections are modulated by the volitional component induced by the action observed. In this study, using a paired pulse transcranial magnetic stimulation (ppTMS) method, we evaluated the excitability of PMv-M1 connections during the observation of videos showing a human hand reaching to grasp a ball (naturalistic grasping video) or a switched on soldering iron (noxious grasping video). The results show that the observation of the naturalistic grasping action increased the M1 excitability and changed the strength of the PMv-M1 connections. The observation of the noxious grasping action did not induce any change in the excitability of the PMv-M1 connections throughout the video, but the strength of PMv-M1 connectivity was reduced. These results demonstrate that the PMv-M1 connections are modulated differently depending on whether the action observed would or would not be performed in real life. 2010. Published by Elsevier Ltd. All rights reserved.

  3. Excitability changes in primary motor cortex just prior to voluntary muscle relaxation.

    PubMed

    Suzuki, Tomotaka; Sugawara, Kenichi; Takagi, Mineko; Higashi, Toshio

    2015-01-01

    We postulated that primary motor cortex (M1) activity does not just decrease immediately prior to voluntary muscle relaxation; rather, it is dynamic and acts as an active cortical process. Thus we investigated the detailed time course of M1 excitability changes during muscle relaxation. Ten healthy participants performed a simple reaction time task. After the go signal, they rapidly terminated isometric abduction of the right index finger from a constant muscle force output of 20% of their maximal voluntary contraction force and performed voluntary muscle relaxation. Transcranial magnetic stimulation pulses were randomly delivered before and after the go signal, and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle. We selected the time course relative to an appropriate reference point, the onset of voluntary relaxation, to detect excitability changes in M1. MEP amplitude from 80 to 60 ms before the estimated electromyographic offset was significantly greater than that in other intervals. Dynamic excitability changes in M1 just prior to quick voluntary muscle relaxation indicate that cortical control of muscle relaxation is established through active processing and not by simple cessation of activity. The cortical mechanisms underlying muscle relaxation need to be reconsidered in light of such dynamics. Copyright © 2015 the American Physiological Society.

  4. Reduced functional connectivity within the primary motor cortex of patients with brachial plexus injury.

    PubMed

    Fraiman, D; Miranda, M F; Erthal, F; Buur, P F; Elschot, M; Souza, L; Rombouts, S A R B; Schimmelpenninck, C A; Norris, D G; Malessy, M J A; Galves, A; Vargas, C D

    2016-01-01

    This study aims at the effects of traumatic brachial plexus lesion with root avulsions (BPA) upon the organization of the primary motor cortex (M1). Nine right-handed patients with a right BPA in whom an intercostal to musculocutaneous (ICN-MC) nerve transfer was performed had post-operative resting state fMRI scanning. The analysis of empirical functional correlations between neighboring voxels revealed faster correlation decay as a function of distance in the M1 region corresponding to the arm in BPA patients as compared to the control group. No differences between the two groups were found in the face area. We also investigated whether such larger decay in patients could be attributed to a gray matter diminution in M1. Structural imaging analysis showed no difference in gray matter density between groups. Our findings suggest that the faster decay in neighboring functional correlations without significant gray matter diminution in BPA patients could be related to a reduced activity in intrinsic horizontal connections in M1 responsible for upper limb motor synergies.

  5. Evolution of fMRI Activation in the Perilesional Primary Motor Cortex and Cerebellum With Rehabilitation Training-Related Motor Gains After Stroke: A Pilot Study

    PubMed Central

    Dong, Yun; Winstein, Carolee J.; Albistegui-DuBois, Richard; Dobkin, Bruce H.

    2014-01-01

    Background Previous studies report that motor recovery after partial destruction of the primary motor cortex (M1) may be associated with adaptive functional reorganization within spared M1. Objective To test feasible methodologies for evaluating relationships between behavioral gains facilitated by rehabilitative training and functional adaptations in perilesional M1 and the cerebellum. Methods Four patients with hemiparesis for more than 3 months after a cortical lesion partially within M1 and 12 healthy volunteers participated. Functional magnetic resonance imaging (fMRI) using a finger-tapping task and concurrent behavioral assessments, including the Fugl-Meyer Motor Assessment of the upper extremity and the Wolf Motor Function Test, were conducted before and after 2 weeks of arm-focused training; 2 patients were further examined 6 and 12 months later to evaluate long-term persistence of brain-behavior adaptations. Results All patients showed higher activation magnitude in perilesional M1 than healthy controls before and after therapy. Further long-term functional gains paralleled the decrease of activation magnitude in perilesional M1 in the 2 more impaired cases. Conclusion The evolution of suggestive correlations between serial scans of fMRI adaptive activity within the primary motor cortex and the cerebellum in relation to relevant behavioral changes over the course of 2 weeks of task-specific therapy and then no formal therapy suggests that repeated assessments may be best for monitoring therapy-induced neuroplasticity. This approach may help develop optimal rehabilitation strategies to maximize poststroke motor recovery as well as improve the search for brain-behavior correlations in functional neuroimaging research. PMID:17369516

  6. Neurons in Primary Motor Cortex Encode Hand Orientation in a Reach-to-Grasp Task.

    PubMed

    Ma, Chaolin; Ma, Xuan; Fan, Jing; He, Jiping

    2017-04-07

    It is disputed whether those neurons in the primary motor cortex (M1) that encode hand orientation constitute an independent channel for orientation control in reach-to-grasp behaviors. Here, we trained two monkeys to reach forward and grasp objects positioned in the frontal plane at different orientation angles, and simultaneously recorded the activity of M1 neurons. Among the 2235 neurons recorded in M1, we found that 18.7% had a high correlation exclusively with hand orientation, 15.9% with movement direction, and 29.5% with both movement direction and hand orientation. The distributions of neurons encoding hand orientation and those encoding movement direction were not uniform but coexisted in the same region. The trajectory of hand rotation was reproduced by the firing patterns of the orientation-related neurons independent of the hand reaching direction. These results suggest that hand orientation is an independent component for the control of reaching and grasping activity.

  7. Reference gene for primary culture of prostate cancer cells.

    PubMed

    Souza, Aline Francielle Damo; Brum, Ilma Simoni; Neto, Brasil Silva; Berger, Milton; Branchini, Gisele

    2013-04-01

    Selection of reference genes to normalize mRNA levels between samples is critical for gene expression studies because their expression can vary depending on the tissues or cells used and the experimental conditions. We performed ten cell cultures from samples of prostate cancer. Cells were divided into three groups: control (with no transfection protocol), cells transfected with siRNA specific to knockdown the androgen receptor and cells transfected with inespecific siRNAs. After 24 h, mRNA was extracted and gene expression was analyzed by Real-time qPCR. Nine candidates to reference genes for gene expression studies in this model were analyzed (aminolevulinate, delta-, synthase 1 (ALAS1); beta-actin (ACTB); beta-2-microglobulin (B2M); glyceraldehyde-3-phosphate dehydrogenase (GAPDH); hypoxanthine phosphoribosyltransferase 1 (HPRT1); succinate dehydrogenase complex, subunit A, flavoprotein (Fp) (SDHA); TATA box binding protein (TBP); ubiquitin C (UBC); tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide (YWHAZ)). Expression stability was calculated NormFinder algorithm to find the most stable genes. NormFinder calculated SDHA as the most stable gene and the gene with the lowest intergroup and intragroup variation, and indicated GAPDH and SDHA as the best combination of two genes for the purpose of normalization. Androgen receptor mRNA expression was evaluated after normalization by each candidate gene and showed statistical difference in the transfected group compared to control group only when normalized by combination of GAPDH and SDHA. Based on the algorithm analysis, the combination of SDHA and GAPDH should be used to normalize target genes mRNA levels in primary culture of prostate cancer cells submitted to transfection with siRNAs.

  8. Accumulation of iron oxide nanoparticles by cultured primary neurons.

    PubMed

    Petters, Charlotte; Dringen, Ralf

    2015-02-01

    Magnetic iron oxide nanoparticles (IONPs) are frequently used for biomedical applications. Although nanoparticles can enter the brain, little is known so far on the uptake of IONPs in neurons and on their neurotoxic potential. Hence, we applied dimercaptosuccinate (DMSA)-coated IONPs to cultured primary rat cerebellar granule neurons. These IONPs had average hydrodynamic diameters of around 80 nm and 120 nm when dispersed in incubation medium in the absence and the presence of 10% fetal calf serum, respectively. Acute exposure of neurons with IONPs for up to 6 h did neither alter the cell morphology nor compromise cell viability, although neurons accumulated large amounts of IONPs in a time- and concentration-dependent manner which caused delayed toxicity. For the first 30 min of incubation of neurons at 37 °C with IONPs the cellular iron content increased proportionally to the concentration of IONPs applied irrespective of the absence and the presence of serum. IONP-exposure in the absence of serum generated maximal cellular iron contents of around 3000 nmol iron/mg protein after 4 h of incubation, while the accumulation in the presence of 10% serum was slower and reached already within 1 h maximal values of around 450 nmol iron/mg protein. For both incubation conditions was the increase in cellular iron contents significantly lowered by reducing the incubation temperature to 4 °C. Application of inhibitors of endocytotic pathways did not affect neuronal IONP accumulation in the absence of serum, while inhibitors of clathrin-mediated endocytosis lowered significantly the IONP accumulation in the presence of serum. These data demonstrate that DMSA-coated IONPs are not acutely toxic to cultured neurons and that a protein corona around the particles strongly affects their interaction with neurons. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Interspecies differences in metabolism of arsenic by cultured primary hepatocytes

    SciTech Connect

    Drobna, Zuzana; Walton, Felecia S.; Harmon, Anne W.; Thomas, David J.; Styblo, Miroslav

    2010-05-15

    Biomethylation is the major pathway for the metabolism of inorganic arsenic (iAs) in many mammalian species, including the human. However, significant interspecies differences have been reported in the rate of in vivo metabolism of iAs and in yields of iAs metabolites found in urine. Liver is considered the primary site for the methylation of iAs and arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in this pathway. Thus, the As3mt-catalyzed methylation of iAs in the liver determines in part the rate and the pattern of iAs metabolism in various species. We examined kinetics and concentration-response patterns for iAs methylation by cultured primary hepatocytes derived from human, rat, mice, dog, rabbit, and rhesus monkey. Hepatocytes were exposed to [{sup 73}As]arsenite (iAs{sup III}; 0.3, 0.9, 3.0, 9.0 or 30 nmol As/mg protein) for 24 h and radiolabeled metabolites were analyzed in cells and culture media. Hepatocytes from all six species methylated iAs{sup III} to methylarsenic (MAs) and dimethylarsenic (DMAs). Notably, dog, rat and monkey hepatocytes were considerably more efficient methylators of iAs{sup III} than mouse, rabbit or human hepatocytes. The low efficiency of mouse, rabbit and human hepatocytes to methylate iAs{sup III} was associated with inhibition of DMAs production by moderate concentrations of iAs{sup III} and with retention of iAs and MAs in cells. No significant correlations were found between the rate of iAs methylation and the thioredoxin reductase activity or glutathione concentration, two factors that modulate the activity of recombinant As3mt. No associations between the rates of iAs methylation and As3mt protein structures were found for the six species examined. Immunoblot analyses indicate that the superior arsenic methylation capacities of dog, rat and monkey hepatocytes examined in this study may be associated with a higher As3mt expression. However, factors other than As3mt expression may also contribute to

  10. Induction of apoptosis by thrombin in the cultured neurons of dorsal motor nucleus of the vagus.

    PubMed

    Wu, X; Zhang, W; Li, J-Y; Chai, B-X; Peng, J; Wang, H; Mulholland, M W

    2011-03-01

    A previous study demonstrated the presence of protease-activated receptor (PAR) 1 and 2 in the dorsal motor nucleus of vagus (DMV). The aim of this study is to characterize the effect of thrombin on the apoptosis of DMV neurons. The dorsal motor nucleus of vagus neurons were isolated from neonatal rat brainstems using micro-dissection and enzymatic digestion and cultured. Apoptosis of DMV neurons were examined in cultured neurons. Apoptotic neuron was examined by TUNEL and ELISA. Data were analyzed using anova and Student's t-test. Exposure of cultured DMV neurons to thrombin (0.1 to 10 U mL(-1)) for 24 h significantly increased apoptosis. Pretreatment of DMV neurons with hirudin attenuated the apoptotic effect of thrombin. Similar induction of apoptosis was observed for the PAR1 receptor agonist SFLLR, but not for the PAR3 agonist TFRGAP, nor for the PAR4 agonist YAPGKF. Protease-activated receptors 1 receptor antagonist Mpr(Cha) abolished the apoptotic effect of thrombin, while YPGKF, a specific antagonist for PAR4, demonstrated no effect. After administration of thrombin, phosphorylation of JNK and P38 occurred as early as 15 min, and remained elevated for up to 45 min. Pretreatment of DMV neurons with SP600125, a specific inhibitor for JNK, or SB203580, a specific inhibitor for P38, significantly inhibited apoptosis induced by thrombin. Thrombin induces apoptosis in DMV neurons through a mechanism involving the JNK and P38 signaling pathways. © 2010 Blackwell Publishing Ltd.

  11. Accumulation of pyrethroid compounds in primary cultures of rat cortical neurons

    EPA Science Inventory

    Recent studies have demonstrated that lipophilic compounds (e.g. methylmercury, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs)) rapidly accumulate in cells in culture to concentrations much higher than in the surrounding media. Primary cultures of neur...

  12. Accumulation of pyrethroid compounds in primary cultures of rat cortical neurons

    EPA Science Inventory

    Recent studies have demonstrated that lipophilic compounds (e.g. methylmercury, polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs)) rapidly accumulate in cells in culture to concentrations much higher than in the surrounding media. Primary cultures of neur...

  13. The effects of rTMS over the primary motor cortex: the link between action and language.

    PubMed

    Repetto, Claudia; Colombo, Barbara; Cipresso, Pietro; Riva, Giuseppe

    2013-01-01

    Is the primary motor cortex (M1) necessary for language comprehension? The present study investigates the role of the primary motor cortex during verbs comprehension, within the framework of the embodied theories of language. We applied rTMS over the right and left hand portion of M1 and tested the effects of the stimulation toward the processing of hand-related action verbs versus abstract verbs. Results underlined a specific inhibition effect following left stimulation, only with hand-related action verbs. These findings seem to corroborate the hypothesis of a functional role of M1 in action verbs comprehension.

  14. Preparation of extracellular matrices produced by cultured and primary fibroblasts

    PubMed Central

    Franco-Barraza, Janusz; Beacham, Dorothy A.; Amatangelo, Michael D.; Cukierman, Edna

    2016-01-01

    Fibroblasts secrete and organize extracellular matrix (ECM), which provides structural support for their adhesion, migration, and tissue organization, besides regulating cellular functions such as growth and survival. Cell-to-matrix interactions are vital for vertebrate development. Disorders in these processes have been associated with fibrosis, developmental malformations, cancer, and other diseases. This unit describes a method for preparing a three-dimensional matrix derived from fibroblastic cells; the matrix is three-dimensional, cell and debris free, and attached to a two-dimensional culture surface. Cell adhesion and spreading are normal on these matrices. This matrix can also be compressed into a two-dimensional matrix and solubilized to study the matrix biochemically. Culturing fibroblasts on traditional two-dimensional (2-D) substrates induces an artificial polarity between lower and upper surfaces of these normally nonpolar cells. Not surprisingly, fibroblast morphology and migration differ once suspended in three-dimensional (3-D) collagen gels (Friedl and Brocker, 2000). However, the molecular composition of collagen gels does not mimic the natural fibroblast (i.e., mesenchymal) microenvironment. Fibroblasts secrete and organize ECM, which provides structural support for their adhesion, migration, and tissue organization, in addition to regulating cellular functions such as growth and survival (Buck and Horwitz, 1987; Hay, 1991; Hynes, 1999; Geiger et al., 2001). Cell-to-matrix interactions are vital for vertebrate development. Disorders in these processes have been associated with fibrosis, developmental malformations, cancer (i.e., desmoplastic tumor microenvironment), and other diseases (Rybinski et al., 2014). This unit describes methods for generating tissue culture surfaces coated with a fibroblast-derived 3-D ECM produced and deposited by both established and primary fibroblasts. The matrices closely resemble in vivo mesenchymal matrices and

  15. Transport Mechanism of Nicotine in Primary Cultured Alveolar Epithelial Cells.

    PubMed

    Takano, Mikihisa; Nagahiro, Machi; Yumoto, Ryoko

    2016-02-01

    Nicotine is absorbed from the lungs into the systemic circulation during cigarette smoking. However, there is little information concerning the transport mechanism of nicotine in alveolar epithelial cells. In this study, we characterized the uptake of nicotine in rat primary cultured type II (TII) and transdifferentiated type I-like (TIL) epithelial cells. In both TIL and TII cells, [(3)H]nicotine uptake was time and temperature-dependent, and showed saturation kinetics. [(3)H]Nicotine uptake in these cells was not affected by Na(+), but was sensitive to extracellular and intracellular pH, suggesting the involvement of a nicotine/proton antiport system. The uptake of [(3)H]nicotine in these cells was potently inhibited by organic cations such as clonidine, diphenhydramine, and pyrilamine, but was not affected by substrates and/or inhibitors of known organic cation transporters such as carnitine, 1-methyl-4-phenylpyridinium, and tetraethylammonium. In addition, the uptake of [(3)H]nicotine in TIL cells was stimulated by preloading the cells with unlabeled nicotine, pyrilamine, and diphenhydramine, but not with tetraethylammonium. These results suggest that a novel proton-coupled antiporter is involved in the uptake of nicotine in alveolar epithelial cells and its absorption from the lungs into the systemic circulation.

  16. Aniline Induces Oxidative Stress and Apoptosis of Primary Cultured Hepatocytes.

    PubMed

    Wang, Yue; Gao, Hong; Na, Xiao-Lin; Dong, Shu-Ying; Dong, Hong-Wei; Yu, Jia; Jia, Li; Wu, Yong-Hui

    2016-11-30

    The toxicity and carcinogenicity of aniline in humans and animals have been well documented. However, the molecular mechanism involved in aniline-induced liver toxicity and carcinogenesis remains unclear. In our research, primary cultured hepatocytes were exposed to aniline (0, 1.25, 2.50, 5.0 and 10.0 μg/mL) for 24 h in the presence or absence of N-acetyl-l-cysteine (NAC). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT), mitochondrial membrane potential, DNA damage, cell viability, and apoptosis were detected. Levels of ROS and MDA were significantly increased and levels of GSH and CAT, activity of SOD, and mitochondrial membrane potential in hepatocytes were significantly decreased by aniline compared with the negative control group. The tail moment and DNA content of the tail in exposed groups were significantly higher than those in the negative control group. Cell viability was reduced and apoptotic death was induced by aniline in a concentration-dependent manner. The phenomena of ROS generation, oxidative damage, loss of mitochondrial membrane potential, DNA damage and apoptosis could be prevented if ROS inhibitor NAC was added. ROS generation is involved in the loss of mitochondrial membrane potential and DNA injury, which may play a role in aniline-induced apoptosis in hepatocytes. Our study provides insight into the mechanism of aniline-induced toxicity and apoptosis of hepatocytes.

  17. Mitochondrial-dependent manganese neurotoxicity in rat primary astrocyte cultures

    PubMed Central

    Yin, Zhaoobao; Aschner, Judy L.; Santos, Ana Paula dos; Aschner, Michael

    2008-01-01

    Chronic exposure to excessive levels of Mn results in a movement disorder termed manganism, which resembles Parkinson’s disease (PD). The pathogenic mechanisms underlying this disorder are not fully understood. Several lines of evidence implicate astrocytes as an early target of Mn neurotoxicity. In the present study, we investigated the effects of Mn on mitochondrial function. Primary astrocyte cultures were prepared from cerebral cortices of one-day-old Sprague–Dawley rats. We have examined the cellular toxicity of Mn and its effects on the phosphorylation of extracellular signal-regulated kinase (ERK) and activation of the precursor protein of caspase-3. The potentiometric dye, tetramethylrhodamine ethyl ester (TMRE), was used to assess the effect of Mn on astrocytic mitochondrial inner membrane potential (ΔΨm). Our studies show that, in a concentration-dependent manner, Mn induces significant (p<0.05) activation of astrocyte caspase-3 and phosphorylated extracellular signal-regulated kinase (p-ERK). Mn treatment (1 and 6 hrs) also significantly (p<0.01) dissipates the ΔΨm in astrocytes as evidenced by a decrease in mitochondrial TMRE fluorescence. These results suggest that activations of astrocytic caspase-3 and ERK are involved in Mn-induced neurotoxicity via mitochondrial-dependent pathways. PMID:18313649

  18. Aniline Induces Oxidative Stress and Apoptosis of Primary Cultured Hepatocytes

    PubMed Central

    Wang, Yue; Gao, Hong; Na, Xiao-Lin; Dong, Shu-Ying; Dong, Hong-Wei; Yu, Jia; Jia, Li; Wu, Yong-Hui

    2016-01-01

    The toxicity and carcinogenicity of aniline in humans and animals have been well documented. However, the molecular mechanism involved in aniline-induced liver toxicity and carcinogenesis remains unclear. In our research, primary cultured hepatocytes were exposed to aniline (0, 1.25, 2.50, 5.0 and 10.0 μg/mL) for 24 h in the presence or absence of N-acetyl-l-cysteine (NAC). Levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT), mitochondrial membrane potential, DNA damage, cell viability, and apoptosis were detected. Levels of ROS and MDA were significantly increased and levels of GSH and CAT, activity of SOD, and mitochondrial membrane potential in hepatocytes were significantly decreased by aniline compared with the negative control group. The tail moment and DNA content of the tail in exposed groups were significantly higher than those in the negative control group. Cell viability was reduced and apoptotic death was induced by aniline in a concentration-dependent manner. The phenomena of ROS generation, oxidative damage, loss of mitochondrial membrane potential, DNA damage and apoptosis could be prevented if ROS inhibitor NAC was added. ROS generation is involved in the loss of mitochondrial membrane potential and DNA injury, which may play a role in aniline-induced apoptosis in hepatocytes. Our study provides insight into the mechanism of aniline-induced toxicity and apoptosis of hepatocytes. PMID:27916916

  19. Primary neuron culture for nerve growth and axon guidance studies in zebrafish (Danio rerio).

    PubMed

    Chen, Zheyan; Lee, Han; Henle, Steven J; Cheever, Thomas R; Ekker, Stephen C; Henley, John R

    2013-01-01

    Zebrafish (Danio rerio) is a widely used model organism in genetics and developmental biology research. Genetic screens have proven useful for studying embryonic development of the nervous system in vivo, but in vitro studies utilizing zebrafish have been limited. Here, we introduce a robust zebrafish primary neuron culture system for functional nerve growth and guidance assays. Distinct classes of central nervous system neurons from the spinal cord, hindbrain, forebrain, and retina from wild type zebrafish, and fluorescent motor neurons from transgenic reporter zebrafish lines, were dissociated and plated onto various biological and synthetic substrates to optimize conditions for axon outgrowth. Time-lapse microscopy revealed dynamically moving growth cones at the tips of extending axons. The mean rate of axon extension in vitro was 21.4±1.2 µm hr(-1) s.e.m. for spinal cord neurons, which corresponds to the typical ∼0.5 mm day(-1) growth rate of nerves in vivo. Fluorescence labeling and confocal microscopy demonstrated that bundled microtubules project along axons to the growth cone central domain, with filamentous actin enriched in the growth cone peripheral domain. Importantly, the growth cone surface membrane expresses receptors for chemotropic factors, as detected by immunofluorescence microscopy. Live-cell functional assays of axon extension and directional guidance demonstrated mammalian brain-derived neurotrophic factor (BDNF)-dependent stimulation of outgrowth and growth cone chemoattraction, whereas mammalian myelin-associated glycoprotein inhibited outgrowth. High-resolution live-cell Ca(2+)-imaging revealed local elevation of cytoplasmic Ca(2+) concentration in the growth cone induced by BDNF application. Moreover, BDNF-induced axon outgrowth, but not basal outgrowth, was blocked by treatments to suppress cytoplasmic Ca(2+) signals. Thus, this primary neuron culture model system may be useful for studies of neuronal development, chemotropic axon

  20. Neurofilament RNA causes neurodegeneration with accumulation of ubiquitinated aggregates in cultured motor neurons.

    PubMed

    Lin, Hong; Zhai, Jinbin; Nie, Zhenying; Wu, Junhua; Meinkoth, Judy L; Schlaepfer, William W; Cañete-Soler, Rafaela

    2003-09-01

    The mechanisms whereby mutant gene expression triggers neurodegeneration are poorly understood but have generally been attributed to translated gene products. We now demonstrate direct neuropathic effects of untranslated RNA on cultured motor neurons. We show that expression of untranslated light neurofilament (NF-L) RNA sequence in the 3'UTR of an EGFP transgene (pEGFP/NF-L RNA) or in a separate expression vector (pRc/NF-L RNA) causes dose-dependent, neuron-specific motor neuron degeneration. Neither unfused EGFP protein (pEGFP/wt) nor EGFP-tagged NF-L protein (pEGFP/NF-L protein) has similar neuropathic effects. The findings are the first demonstration of a direct RNA-mediated neurotoxic effect. Moreover, the resulting neuropathological changes show that untranslated RNA can lead to early degeneration of neuritic processes and accumulations of ubiquitinated aggregates in the perikarya and nuclei of degenerating motor neurons. The latter findings are hallmark neuropathological features of neurodegenerative diseases and their occurrence as a result of altered RNA expression raises the prospects of an RNA-mediated component in the pathogenesis of neurodegenerative states.

  1. Modification of Existing Human Motor Memories Is Enabled by Primary Cortical Processing during Memory Reactivation

    PubMed Central

    Censor, Nitzan; Dimyan, Michael A.; Cohen, Leonardo G.

    2010-01-01

    Summary One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1–4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject’s brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications. PMID:20817532

  2. Cortical involvement in the sensory and motor symptoms of primary restless legs syndrome.

    PubMed

    Tyvaert, L; Houdayer, E; Devanne, H; Bourriez, J L; Derambure, P; Monaca, C

    2009-12-01

    Restless legs syndrome (RLS) is characterized by closely interrelated motor and sensory disorders. Two types of involuntary movement can be observed: periodic leg movements during wakefulness (PLMW) and periodic leg movements during sleep (PLMS). Basal ganglia dysfunction in primary RLS has often been suggested. However, clinical observations raise the hypothesis of sensorimotor cortical involvement in RLS symptoms. Here, we explored cortical function via movement-related beta and mu rhythm reactivity. Twelve patients with idiopathic, primary RLS were investigated and compared with 10 healthy subjects. In the patient group, we analyzed event-related beta and mu (de)synchronization (ERD/S) for PLMS and PLMW during a suggested immobilization test (SIT). An ERD/S analysis was also performed in patients and controls during self-paced right ankle dorsal flexion at 8:30 PM (i.e., the symptomatic period for patients) and 8:30 AM (the asymptomatic period). Before PLMS, there was no ERD. Intense ERS was recorded after PLMS. As with voluntary movement, cortical ERD was always observed before PLMW. After PLMW, ERS had a diffuse scalp distribution. Furthermore, the ERS and ERD amplitudes and durations for voluntary movement were greater during the symptomatic period than during the asymptomatic period and in comparison with healthy controls, who presented an evening decrease in these parameters. Patients and controls had similar ERD and ERS patterns in the morning. On the basis of a rhythm reactivity study, we conclude that the symptoms of RLS are related to cortical sensorimotor dysfunction.

  3. Primary motor cortex activity reduction under the regulation of SMA by real-time fMRI

    NASA Astrophysics Data System (ADS)

    Guo, Jia; Zhao, Xiaojie; Li, Yi; Yao, Li; Chen, Kewei

    2012-03-01

    Real-time fMRI (rtfMRI) is a new technology which allows human subjects to observe and control their own BOLD signal change from one or more localized brain regions during scanning. Current rtfMRI-neurofeedback studies mainly focused on the target region itself without considering other related regions influenced by the real-time feedback. However, there always exits important directional influence between many of cooperative regions. On the other hand, rtfMRI based on motor imagery mainly aimed at somatomotor cortex or primary motor area, whereas supplement motor area (SMA) was a relatively more integrated and pivotal region. In this study, we investigated whether the activities of SMA can be controlled utilizing different motor imagery strategies, and whether there exists any possible impact on an unregulated but related region, primary motor cortex (M1). SMA was first localized using overt finger tapping task, the activities of SMA were feedback to subjects visually on line during each of two subsequent imagery motor movement sessions. All thirteen healthy participants were found to be able to successfully control their SMA activities by self-fit imagery strategies which involved no actual motor movements. The activation of right M1 was also found to be significantly reduced in both intensity and extent with the neurofeedback process targeted at SMA, suggestive that not only the part of motor cortex activities were influenced under the regulation of a key region SMA, but also the increased difference between SMA and M1 might reflect the potential learning effect.

  4. Role of the primary motor and dorsal premotor cortices in the anticipation of forces during object lifting.

    PubMed

    Chouinard, Philippe A; Leonard, Gabriel; Paus, Tomás

    2005-03-02

    When lifting small objects, people apply forces that match the expected weight of the object. This expectation relies in part on information acquired during a previous lift and on associating a certain weight with a particular object. Our study examined the role of the primary motor and dorsal premotor cortices in predicting weight based either on information acquired during a previous lift (no-cue experiment) or on arbitrary color cues associated with a particular weight (cue experiment). In the two experiments, subjects used precision grip to lift two different weights in a series of trials both before and after we applied low-frequency repetitive transcranial magnetic stimulation over the primary motor and dorsal premotor cortices. In the no-cue experiment, subjects did not receive any previous information about which of two weights they would have to lift. In the cue experiment, a color cue provided information about which of the two weights subjects would have to lift. Our results demonstrate a double dissociation in the effects induced by repetitive stimulation. When applied over the primary motor cortex, repetitive stimulation disrupted the scaling of forces based on information acquired during a previous lift. In contrast, when applied over the dorsal premotor cortex, repetitive stimulation disrupted the scaling of forces based on arbitrary color cues. We conclude that the primary motor and dorsal premotor cortices have unique roles during the anticipatory scaling of forces associated with the lifting of different weights.

  5. Preparing Pre-Service Primary School Teachers to Assess Fundamental Motor Skills: Two Skills and Two Approaches

    ERIC Educational Resources Information Center

    Haynes, John; Miller, Judith

    2015-01-01

    Background: Pre-service teacher education (PSTE) programmes for generalist primary school teachers have limited time allocated to Physical Education, Health and Personal Development. In practice, teachers in schools are required to assess motor skills despite the fact that their training provides minimal preparation. This necessitates creative…

  6. Preparing Pre-Service Primary School Teachers to Assess Fundamental Motor Skills: Two Skills and Two Approaches

    ERIC Educational Resources Information Center

    Haynes, John; Miller, Judith

    2015-01-01

    Background: Pre-service teacher education (PSTE) programmes for generalist primary school teachers have limited time allocated to Physical Education, Health and Personal Development. In practice, teachers in schools are required to assess motor skills despite the fact that their training provides minimal preparation. This necessitates creative…

  7. Central Motor Conduction Studies and Diagnostic Magnetic Resonance Imaging in Children with Severe Primary and Secondary Dystonia

    ERIC Educational Resources Information Center

    McClelland, Verity; Mills, Kerry; Siddiqui, Ata; Selway, Richard; Lin, Jean-Pierre

    2011-01-01

    Aim: Dystonia in childhood has many causes. Imaging may suggest corticospinal tract dysfunction with or without coexistent basal ganglia damage. There are very few published neurophysiological studies on children with dystonia; one previous study has focused on primary dystonia. We investigated central motor conduction in 62 children (34 males, 28…

  8. Central Motor Conduction Studies and Diagnostic Magnetic Resonance Imaging in Children with Severe Primary and Secondary Dystonia

    ERIC Educational Resources Information Center

    McClelland, Verity; Mills, Kerry; Siddiqui, Ata; Selway, Richard; Lin, Jean-Pierre

    2011-01-01

    Aim: Dystonia in childhood has many causes. Imaging may suggest corticospinal tract dysfunction with or without coexistent basal ganglia damage. There are very few published neurophysiological studies on children with dystonia; one previous study has focused on primary dystonia. We investigated central motor conduction in 62 children (34 males, 28…

  9. Coherent corticomuscular oscillations originate from primary motor cortex: evidence from patients with early brain lesions.

    PubMed

    Gerloff, Christian; Braun, Christoph; Staudt, Martin; Hegner, Yiwen Li; Dichgans, Johannes; Krägeloh-Mann, Ingeborg

    2006-10-01

    Coherent oscillations of neurons in the primary motor cortex (M1) have been shown to be involved in the corticospinal control of muscle activity. This interaction between M1 and muscle can be measured by the analysis of corticomuscular coherence in the beta-frequency range (beta-CMCoh; 14-30 Hz). Largely based on magnetoencephalographic (MEG) source-modeling data, it is widely assumed that beta-CMCoh reflects direct coupling between M1 and muscle. Deafferentation is capable of modulating beta-CMCoh, however, and therefore the influence of reafferent somatosensory signaling and corresponding neuronal activity in the somatosensory cortex (S1) has been unclear. We present transcranial magnetic stimulation (TMS) and MEG data from three adult patients suffering from congenital hemiparesis due to pre- and perinatally acquired lesions of the pyramidal tract. In these patients, interhemispheric reorganization had resulted in relocation of M1 to the contralesional hemisphere, ipsilateral to the paretic hand, whereas S1 had remained in the lesioned hemisphere. This topographic dichotomy allowed for an unequivocal topographic differentiation of M1 and S1 with MEG (which is not possible if M1 and S1 are directly adjacent within one hemisphere). In all patients, beta-CMCoh originated from the contralesional M1, in accordance with the TMS-evoked motor responses, and in contrast to the somatosensory evoked fields (SEFs) for which the sources (N20m) were localized in S1 of the lesioned hemisphere. These data provide direct evidence for the concept that beta-CMCoh reflects the motorcortical efferent drive from M1 to the spinal motoneuron pool and muscle. No evidence was found for a relevant contribution of neuronal activity in S1 to beta-CMCoh.

  10. Direction of Movement Is Encoded in the Human Primary Motor Cortex

    PubMed Central

    Toxopeus, Carolien M.; de Jong, Bauke M.; Valsan, Gopal; Conway, Bernard A.; Leenders, Klaus L.; Maurits, Natasha M.

    2011-01-01

    The present study investigated how direction of hand movement, which is a well-described parameter in cerebral organization of motor control, is incorporated in the somatotopic representation of the manual effector system in the human primary motor cortex (M1). Using functional magnetic resonance imaging (fMRI) and a manual step-tracking task we found that activation patterns related to movement in different directions were spatially disjoint within the representation area of the hand on M1. Foci of activation related to specific movement directions were segregated within the M1 hand area; activation related to direction 0° (right) was located most laterally/superficially, whereas directions 180° (left) and 270° (down) elicited activation more medially within the hand area. Activation related to direction 90° was located between the other directions. Moreover, by investigating differences between activations related to movement along the horizontal (0°+180°) and vertical (90°+270°) axis, we found that activation related to the horizontal axis was located more anterolaterally/dorsally in M1 than for the vertical axis, supporting that activations related to individual movement directions are direction- and not muscle related. Our results of spatially segregated direction-related activations in M1 are in accordance with findings of recent fMRI studies on neural encoding of direction in human M1. Our results thus provide further evidence for a direct link between direction as an organizational principle in sensorimotor transformation and movement execution coded by effector representations in M1. PMID:22110768

  11. Properties of primary motor cortex output to hindlimb muscles in the macaque monkey

    PubMed Central

    Hudson, Heather M.; Griffin, Darcy M.; Belhaj-Saïf, Abderraouf

    2014-01-01

    The cortical control of forelimb motor function has been studied extensively, especially in the primate. In contrast, cortical control of the hindlimb has been relatively neglected. This study assessed the output properties of the primary motor cortex (M1) hindlimb representation in terms of the sign, latency, magnitude, and distribution of effects in stimulus-triggered averages (StTAs) of electromyography (EMG) activity recorded from 19 muscles, including hip, knee, ankle, digit, and intrinsic foot muscles, during a push-pull task compared with data reported previously on the forelimb. StTAs (15, 30, and 60 μA at 15 Hz) of EMG activity were computed at 317 putative layer V sites in two rhesus macaques. Poststimulus facilitation (PStF) was distributed equally between distal and proximal muscles, whereas poststimulus suppression (PStS) was more common in distal muscles than proximal muscles (51/49%, respectively, for PStF; 72/28%, respectively, for PStS) at 30 μA. Mean PStF and PStS onset latency generally increased the more distal the joint of a muscle's action. Most significantly, the average magnitude of hindlimb poststimulus effects was considerably weaker than the average magnitude of effects from forelimb M1. In addition, forelimb PStF magnitude increased consistently from proximal to distal joints, whereas hindlimb PStF magnitude was similar at all joints except the intrinsic foot muscles, which had a magnitude of approximately double that of all of the other muscles. The results suggest a greater monosynaptic input to forelimb compared with hindlimb motoneurons, as well as a more direct synaptic linkage for the intrinsic foot muscles compared with the other hindlimb muscles. PMID:25411454

  12. Area 5 Influences Excitability within the Primary Motor Cortex in Humans

    PubMed Central

    Premji, Azra; Rai, Navjot; Nelson, Aimee

    2011-01-01

    In non-human primates, Brodmann's area 5 (BA 5) has direct connectivity with primary motor cortex (M1), is largely dedicated to the representation of the hand and may have evolved with the ability to perform skilled hand movement. Less is known about human BA 5 and its interaction with M1 neural circuits related to hand control. The present study examines the influence of BA 5 on excitatory and inhibitory neural circuitry within M1 bilaterally before and after continuous (cTBS), intermittent (iTBS), and sham theta-burst stimulation (sham TBS) over left hemisphere BA 5. Using single and paired-pulse TMS, measurements of motor evoked potentials (MEPs), short interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were quantified for the representation of the first dorsal interosseous muscle. Results indicate that cTBS over BA 5 influences M1 excitability such that MEP amplitudes are increased bilaterally for up to one hour. ITBS over BA 5 results in an increase in MEP amplitude contralateral to stimulation with a delayed onset that persists up to one hour. SICI and ICF were unaltered following TBS over BA 5. Similarly, F-wave amplitude and latency were unaltered following cTBS over BA 5. The data suggest that BA 5 alters M1 output directed to the hand by influencing corticospinal neurons and not interneurons that mediate SICI or ICF circuitry. Targeting BA 5 via cTBS and iTBS is a novel mechanism to powerfully modulate activity within M1 and may provide an avenue for investigating hand control in healthy populations and modifying impaired hand function in clinical populations. PMID:21603571

  13. Regulation of primary motor cortex excitability by repetitive passive finger movement frequency.

    PubMed

    Sasaki, Ryoki; Nakagawa, Masaki; Tsuiki, Shota; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Masaki, Mitsuhiro; Otsuru, Naofumi; Onishi, Hideaki

    2017-08-15

    Somatosensory input induced by passive movement activates primary motor cortex (M1). We applied repetitive passive movement (RPM) of different frequencies to test if modulation of M1 excitability depends on RPM frequency. Twenty-seven healthy subjects participated in this study. Motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) to left M1 were recorded from the right first dorsal interosseous muscle (FDI) to assess corticospinal excitability (experiment 1: n=15), and F-waves were measured from the right FDI as an index of spinal motoneuron excitability (experiment 2: n=15). Passive abduction/adduction of the right index finger was applied for 10min at 0.5, 1.0, 3.0, and 5.0Hz. Both 0.5Hz-RPM and 1.0Hz-RPM decreased MEPs for 2min (p<0.05), and 5.0Hz-RPM decreased MEPs for 15min compared with baseline (p<0.05); however, there was no difference in MEPs after 3.0Hz-RPM. No F-wave changes were observed following any RPM intervention. Based on the results of experiments 1 and 2, we investigated whether RPM modulates cortical inhibitory circuit using the paired-pulse TMS technique (experiment 3: n=12). Short-interval intracortical inhibition (SICI) was measured using paired-pulse TMS (inter-stimulus interval of 3ms) before and after 1.0, 3.0, and 5.0Hz-RPM. Both 1.0 and 5.0Hz-RPM increased SICI compared with baseline (p<0.05). These experiments suggest that M1 excitability decreases after RPM depending on movement frequency, possibly through frequency-dependent enhancement of cortical inhibitory circuit in M1. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Homeostatic-like plasticity of the primary motor hand area is impaired in focal hand dystonia.

    PubMed

    Quartarone, Angelo; Rizzo, Vincenzo; Bagnato, Sergio; Morgante, Francesca; Sant'Angelo, Antonino; Romano, Marcello; Crupi, Domenica; Girlanda, Paolo; Rothwell, John C; Siebner, Hartwig R

    2005-08-01

    The excitability of inhibitory circuits in patients with writer's cramp is reduced at multiple levels within the sensorimotor system, including the primary motor hand area (M1). Although this may play a major role in the pathophysiology of writer's cramp, it is still unclear what factors may cause the imbalance between inhibition and excitation to arise. One possibility is that homeostatic mechanisms that keep cortical excitability within a normal physiological range are impaired. In eight patients with writer's cramp and eight healthy age-matched controls, we combined low-frequency repetitive transcranial magnetic stimulation (rTMS) with transcranial direct current stimulation (TDCS) to probe regional homeostatic plasticity of the left M1. Confirming our previous study (Siebner et al., J Neurosci 2004; 24: 3379-85), 'facilitatory' preconditioning of the M1 with anodal TDCS enhanced the inhibitory effect of subsequent 1 Hz rTMS on corticospinal excitability. Conversely, 'inhibitory' preconditioning with cathodal TDCS reversed the after effect of 1 Hz rTMS, producing an increase in corticospinal excitability. The results were quite different in patients with writer's cramp. Following preconditioning with TDCS, 1 Hz rTMS induced no consistent changes in corticospinal excitability, indicating a loss of the normal 'homeostatic' response pattern. In addition, the normal inhibitory effect of preconditioning with cathodal TDCS was absent. The present data suggest that homeostatic mechanisms that stabilize excitability levels within a useful dynamic range are impaired in patients with writer's cramp. We propose that a faulty homeostatic response to acute increases in corticospinal excitability favours maladaptive motor plasticity. The role of homeostatic-like plasticity in the pathophysiology of task-specific dystonias warrants further study.

  15. Asymmetric Activation of the Primary Motor Cortex during Observation of a Mirror Reflection of a Hand

    PubMed Central

    Tominaga, Wataru; Matsubayashi, Jun; Furuya, Makiko; Matsuhashi, Masao; Mima, Tatsuya; Fukuyama, Hidenao; Mitani, Akira

    2011-01-01

    Mirror therapy is an effective technique for pain relief and motor function recovery. It has been demonstrated that magnetic 20-Hz activity is induced in the primary motor cortex (M1) after median nerve stimulation and that the amount of the stimulus-induced 20-Hz activity is decreased when the M1 is activated. In the present study, we investigated how the image or the mirror reflection of a hand holding a pencil modulates the stimulus-induced 20-Hz activity in the M1. Neuromagnetic brain activity was recorded from 13 healthy right-handed subjects while they were either viewing directly their hand holding a pencil or viewing a mirror reflection of their hand holding a pencil. The 20-Hz activity in the left or the right M1 was examined after the right or the left median nerve stimulation, respectively, and the suppression of the stimulus-induced 20-Hz in the M1 by viewing directly one hand holding a pencil or by viewing the mirror image of the hand holding a pencil was assumed to indicate the activation of the M1. The results indicated that the M1 innervating the dominant hand was suppressed either by viewing directly the dominant hand holding a pencil or by viewing the mirror image of the non-dominant hand holding a pencil. On the other hand, the M1 innervating the non-dominant hand was activated by viewing the mirror image of the dominant hand holding a pencil, but was not activated by viewing directly the non-dominant hand holding a pencil. The M1 innervating either the dominant or the non-dominant hand, however, was not activated by viewing the hand on the side ipsilateral to the M1 examined or the mirror image of the hand on the side contralateral to the M1 exaimined. Such activation of the M1 might induce some therapeutic effects of mirror therapy. PMID:22140555

  16. Interhemispheric interactions between trunk muscle representations of the primary motor cortex.

    PubMed

    Jean-Charles, Loyda; Nepveu, Jean-Francois; Deffeyes, Joan E; Elgbeili, Guillaume; Dancause, Numa; Barthélemy, Dorothy

    2017-09-01

    Unilateral arm movements require trunk stabilization through bilateral contraction of axial muscles. Interhemispheric interactions between primary motor cortices (M1) could enable such coordinated contractions, but these mechanisms are largely unknown. Using transcranial magnetic stimulation (TMS), we characterized interhemispheric interactions between M1 representations of the trunk-stabilizing muscles erector spinae at the first lumbar vertebra (ES L1) during a right isometric shoulder flexion. These interactions were compared with those of the anterior deltoid (AD), the main agonist in this task, and the first dorsal interosseous (FDI). TMS over the right M1 elicited ipsilateral silent periods (iSP) in all three muscles on the right side. In ES L1, but not in AD or FDI, ipsilateral motor evoked potential (iMEP) could precede the iSP or replace it. iMEP amplitude was not significantly different whether ES L1 was used to stabilize the trunk or was voluntarily contracted. TMS at the cervicomedullary junction showed that the size of cervicomedullary evoked potential was unchanged during the iSP but increased during iMEP, suggesting that the iSP, but not the iMEP, is due to intracortical mechanisms. Using a dual-coil paradigm with two coils over the left and right M1, interhemispheric inhibition could be evoked at interstimulus intervals of 6 ms in ES L1 and 8 ms in AD and FDI. Together, these results suggest that interhemispheric inhibition is dominant when axial muscles are involved in a stabilizing task. The ipsilateral facilitation could be evoked by ipsilateral or subcortical pathways and could be used depending on the role axial muscles play in the task.NEW & NOTEWORTHY The mechanisms involved in the bilateral coordination of axial muscles during unilateral arm movement are poorly understood. We thus investigated the nature of interhemispheric interactions in axial muscles during arm motor tasks in healthy subjects. By combining different methodologies, we

  17. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning.

    PubMed

    Jelić, Milan B; Milanović, Sladjan D; Filipović, Saša R

    2015-05-01

    To evaluate the differential effects on motor learning of two types of theta burst stimulation (TBS), the excitatory intermittent TBS (iTBS) and inhibitory continuous TBS (cTBS), if TBS is applied in an early stage of learning process. Thirty right handed healthy people were randomly allocated into one of the three groups according to the intervention applied, iTBS, cTBS or placebo. The interventions and measurements targeted the non-dominant side. The reaction time task (RTT) and Purdue pegboard task (PPT) were used. Measurements and motor tasks were carried out at baseline (T0), immediately after the intervention (T1), and 30 min later (T2). Compared to placebo, following cTBS M1 excitability went down and PPT learning was slowed. Following iTBS M1 excitability increased temporarily and PPT learning pattern changed, but learning was not improved. The MEP and PPT changes induced during the T0-T1 time interval correlated significantly. The early consolidation of the learned material was much more influenced by the TBS induced promotion/suppression of the M1 functional plasticity reserves than by the absolute level of the M1 activation. The results may help to better define the use of TBS in promotion of motor learning in neurorehabilitation and cognitive enhancement. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  18. Glucose metabolism by adult hepatocytes in primary culture and by cell lines from rat liver.

    PubMed

    Bissell, D M; Levine, G A; Bissell, M J

    1978-03-01

    The metabolic fate of [U-14C]glucose has been examined in detail in adult rat hepatocytes in primary monolayer culture, as well as in two permanent cell lines--Buffalo rat liver (BRL) and transplantable rat hepatoma (HTC) cells-derived from normal rat liver and from rat hepatoma, respectively. Under defined conditions of incubation, at a glucose concentration of 5.5 mM, the three types of cultured liver cells exhibited pronounced differences in glucose metabolism. Primary cultures, like the intact liver, differed from the cell lines in consuming relatively small amounts of glucose and converting approximately 50% of the total metabolized glucose to lactate. By contrast, the permantent cell lines consumed glucose at a 40-fold greater rate than did primary cultures, converting 80--90% of the carbohydrate to lactate. Oxidative metabolism of glucose carbon also differed among the three types of liver culture. Of the total [U-14C]glucose consumed, primary cultures converted approximately 30% to labeled CO2 per hour, whereas the liver cell lines converted 5--10%. Finally, glucose metabolism in primary culture exhibited adaptation as hepatocytes aged in culture, shifting progressively toward the pattern exhibited by the permanent cell lines. This change occurred over a time course similar to that for other kinds of functional change in hepatocytes in primary culture and thus may be relevant to the general problem of phenotypic alteration in liver cell culture.

  19. Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex.

    PubMed

    Kidgell, Dawson J; Goodwill, Alicia M; Frazer, Ashlyn K; Daly, Robin M

    2013-07-01

    Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P < 0.05); however there was no difference across time points between unilateral and bilateral stimulation. There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post, 30 minutes and 60 minutes compared to sham stimulation (all P < 0.05). Unilateral and bilateral stimulation reduced short

  20. Induction of cortical plasticity and improved motor performance following unilateral and bilateral transcranial direct current stimulation of the primary motor cortex

    PubMed Central

    2013-01-01

    Background Transcranial direct current stimulation (tDCS) is a non-invasive technique that modulates the excitability of neurons within the primary motor cortex (M1). Research shows that anodal-tDCS applied over the non-dominant M1 (i.e. unilateral stimulation) improves motor function of the non-dominant hand. Similarly, previous studies also show that applying cathodal tDCS over the dominant M1 improves motor function of the non-dominant hand, presumably by reducing interhemispheric inhibition. In the present study, one condition involved anodal-tDCS over the non-dominant M1 (unilateral stimulation) whilst a second condition involved applying cathodal-tDCS over the dominant M1 and anodal-tDCS over non-dominant M1 (bilateral stimulation) to determine if unilateral or bilateral stimulation differentially modulates motor function of the non-dominant hand. Using a randomized, cross-over design, 11 right-handed participants underwent three stimulation conditions: 1) unilateral stimulation, that involved anodal-tDCS applied over the non-dominant M1, 2) bilateral stimulation, whereby anodal-tDCS was applied over the non-dominant M1, and cathodal-tDCS over the dominant M1, and 3) sham stimulation. Transcranial magnetic stimulation (TMS) was performed before, immediately after, 30 and 60 minutes after stimulation to elucidate the neural mechanisms underlying any potential after-effects on motor performance. Motor function was evaluated by the Purdue pegboard test. Results There were significant improvements in motor function following unilateral and bilateral stimulation when compared to sham stimulation at all-time points (all P < 0.05); however there was no difference across time points between unilateral and bilateral stimulation. There was also a similar significant increase in corticomotor excitability with both unilateral and bilateral stimulation immediately post, 30 minutes and 60 minutes compared to sham stimulation (all P < 0.05). Unilateral and bilateral

  1. Primary sensory and motor cortex excitability are co-modulated in response to peripheral electrical nerve stimulation.

    PubMed

    Schabrun, Siobhan M; Ridding, Michael C; Galea, Mary P; Hodges, Paul W; Chipchase, Lucinda S

    2012-01-01

    Peripheral electrical stimulation (PES) is a common clinical technique known to induce changes in corticomotor excitability; PES applied to induce a tetanic motor contraction increases, and PES at sub-motor threshold (sensory) intensities decreases, corticomotor excitability. Understanding of the mechanisms underlying these opposite changes in corticomotor excitability remains elusive. Modulation of primary sensory cortex (S1) excitability could underlie altered corticomotor excitability with PES. Here we examined whether changes in primary sensory (S1) and motor (M1) cortex excitability follow the same time-course when PES is applied using identical stimulus parameters. Corticomotor excitability was measured using transcranial magnetic stimulation (TMS) and sensory cortex excitability using somatosensory evoked potentials (SEPs) before and after 30 min of PES to right abductor pollicis brevis (APB). Two PES paradigms were tested in separate sessions; PES sufficient to induce a tetanic motor contraction (30-50 Hz; strong motor intensity) and PES at sub motor-threshold intensity (100 Hz). PES applied to induce strong activation of APB increased the size of the N(20)-P(25) component, thought to reflect sensory processing at cortical level, and increased corticomotor excitability. PES at sensory intensity decreased the size of the P25-N33 component and reduced corticomotor excitability. A positive correlation was observed between the changes in amplitude of the cortical SEP components and corticomotor excitability following sensory and motor PES. Sensory PES also increased the sub-cortical P(14)-N(20) SEP component. These findings provide evidence that PES results in co-modulation of S1 and M1 excitability, possibly due to cortico-cortical projections between S1 and M1. This mechanism may underpin changes in corticomotor excitability in response to afferent input generated by PES.

  2. Primary Sensory and Motor Cortex Excitability Are Co-Modulated in Response to Peripheral Electrical Nerve Stimulation

    PubMed Central

    Schabrun, Siobhan M.; Ridding, Michael C.; Galea, Mary P.; Hodges, Paul W.; Chipchase, Lucinda S.

    2012-01-01

    Peripheral electrical stimulation (PES) is a common clinical technique known to induce changes in corticomotor excitability; PES applied to induce a tetanic motor contraction increases, and PES at sub-motor threshold (sensory) intensities decreases, corticomotor excitability. Understanding of the mechanisms underlying these opposite changes in corticomotor excitability remains elusive. Modulation of primary sensory cortex (S1) excitability could underlie altered corticomotor excitability with PES. Here we examined whether changes in primary sensory (S1) and motor (M1) cortex excitability follow the same time-course when PES is applied using identical stimulus parameters. Corticomotor excitability was measured using transcranial magnetic stimulation (TMS) and sensory cortex excitability using somatosensory evoked potentials (SEPs) before and after 30 min of PES to right abductor pollicis brevis (APB). Two PES paradigms were tested in separate sessions; PES sufficient to induce a tetanic motor contraction (30–50 Hz; strong motor intensity) and PES at sub motor-threshold intensity (100 Hz). PES applied to induce strong activation of APB increased the size of the N20-P25 component, thought to reflect sensory processing at cortical level, and increased corticomotor excitability. PES at sensory intensity decreased the size of the P25-N33 component and reduced corticomotor excitability. A positive correlation was observed between the changes in amplitude of the cortical SEP components and corticomotor excitability following sensory and motor PES. Sensory PES also increased the sub-cortical P14-N20 SEP component. These findings provide evidence that PES results in co-modulation of S1 and M1 excitability, possibly due to cortico-cortical projections between S1 and M1. This mechanism may underpin changes in corticomotor excitability in response to afferent input generated by PES. PMID:23227260

  3. Effect of Organizational Culture on Patient Access, Care Continuity, and Experience of Primary Care.

    PubMed

    Hung, Dorothy; Chung, Sukyung; Martinez, Meghan; Tai-Seale, Ming

    2016-01-01

    This study examined relationships between organizational culture and patient-centered outcomes in primary care. Generalized least squares regression was used to analyze patient access, care continuity, and reported experiences of care among 357 physicians in 41 primary care departments. Compared with a "Group-oriented" culture, a "Rational" culture type was associated with longer appointment wait times, and both "Hierarchical" and "Developmental" culture types were associated with less care continuity, but better patient experiences with care. Understanding the unique effects of organizational culture can enhance the delivery of more patient-centered care.

  4. Exploring Culture in Locally Published English Textbooks for Primary Education in Turkey

    ERIC Educational Resources Information Center

    Kirkgöz, Yasemin; Agçam, Reyhan

    2011-01-01

    Since language and culture are closely interwoven, the integration of culture into textbooks used for teaching English as a second/foreign language has become a widely accepted phenomenon. This study investigates the cultural elements in locally published English textbooks used for Turkish primary schools following two major curriculum innovations…

  5. Nogo receptor 1 is expressed in both primary cultured glial cells and neurons

    PubMed Central

    Ukai, Junichi; Imagama, Shiro; Ohgomori, Tomohiro; Ito, Zenya; Ando, Kei; Ishiguro, Naoki; Kadomatsu, Kenji

    2016-01-01

    ABSTRACT Nogo receptor (NgR) is common in myelin-derived molecules, i.e., Nogo, MAG, and OMgp, and plays important roles in both axon fasciculation and the inhibition of axonal regeneration. In contrast to NgR’s roles in neurons, its roles in glial cells have been poorly explored. Here, we found a dynamic regulation of NgR1 expression during development and neuronal injury. NgR1 mRNA was consistently expressed in the brain from embryonic day 18 to postnatal day 25. In contrast, its expression significantly decreased in the spinal cord during development. Primary cultured neurons, microglia, and astrocytes expressed NgR1. Interestingly, a contusion injury in the spinal cord led to elevated NgR1 mRNA expression at the injury site, but not in the motor cortex, 14 days after injury. Consistent with this, astrocyte activation by TGFβ1 increased NgR1 expression, while microglia activation rather decreased NgR1 expression. These results collectively suggest that NgR1 expression is enhanced in a milieu of neural injury. Our findings may provide insight into the roles of NgR1 in glial cells. PMID:27578914

  6. The activity in the contralateral primary motor cortex, dorsal premotor and supplementary motor area is modulated by performance gains

    PubMed Central

    Sosnik, Ronen; Flash, Tamar; Sterkin, Anna; Hauptmann, Bjoern; Karni, Avi

    2014-01-01

    There is growing experimental evidence that the engagement of different brain areas in a given motor task may change with practice, although the specific brain activity patterns underlying different stages of learning, as defined by kinematic or dynamic performance indices, are not well understood. Here we studied the change in activation in motor areas during practice on sequences of handwriting-like trajectories, connecting four target points on a digitizing table “as rapidly and as accurately as possible” while lying inside an fMRI scanner. Analysis of the subjects' pooled kinematic and imaging data, acquired at the beginning, middle, and end of the training period, revealed no correlation between the amount of activation in the contralateral M1, PM (dorsal and ventral), supplementary motor area (SMA), preSMA, and Posterior Parietal Cortex (PPC) and the amount of practice per-se. Single trial analysis has revealed that the correlation between the amount of activation in the contralateral M1 and trial mean velocity was partially modulated by performance gains related effects, such as increased hand motion smoothness. Furthermore, it was found that the amount of activation in the contralateral preSMA increased when subjects shifted from generating straight point-to-point trajectories to their spatiotemporal concatenation into a smooth, curved trajectory. Altogether, our results indicate that the amount of activation in the contralateral M1, PMd, and preSMA during the learning of movement sequences is correlated with performance gains and that high level motion features (e.g., motion smoothness) may modulate, or even mask correlations between activity changes and low-level motion attributes (e.g., trial mean velocity). PMID:24795591

  7. Proton NMR characterization of intact primary and metastatic melanoma cells in 2D & 3D cultures.

    PubMed

    Ramachandran, Gokula Krishnan; Yeow, Chen Hua

    2017-03-16

    To characterize the differences between the primary and metastatic melanoma cell lines grown in 2D cultures and 3D cultures. Primary melanoma cells (WM115) and metastatic melanoma cells (WM266) extracted from a single donor was cultured in 2D as well as 3D cultures. These cells were characterized using proton NMR spectrometry, and the qualitative chemical shifts markers were identified and discussed. In monolayer culture (2D), we observed one qualitative chemical shift marker for primary melanoma cells. In spheroid cultures (3D), we observed nine significant chemical shifts, of which eight markers were specific for primary melanoma spheroids, whereas the other one marker was specific to metastatic melanoma spheroids. This study suggests that the glucose accumulation and phospholipid composition vary significantly between the primary and metastatic cells lines that are obtained from a single donor and also with the cell culturing methods. 14 qualitative chemical shift markers were obtained in the comparison between monolayer culture and spheroids cultures irrespective of the differences in the cell lines. Among which 4 were unique to monolayer cultures whereas 10 chemical shifts were unique to the spheroid cultures. This study also shows that the method of cell culture would drastically affect the phospholipid composition of the cells and also depicts that the cells in spheroid culture closely resembles the cells in vivo. This study shows the high specificity of proton NMR spectrometry in characterizing cancer cell lines and also shows the variations in the glucose accumulation and phospholipid composition between the primary and metastatic melanoma cell lines from the same donor. Differences in the cell culture method does plays an important role in phospholipid composition of the cells.

  8. Repetitive transcranial magnetic stimulation of the primary motor cortex in the treatment of motor signs in Parkinson's disease: A quantitative review of the literature.

    PubMed

    Zanjani, Anosha; Zakzanis, Konstantine K; Daskalakis, Zafiris J; Chen, Robert

    2015-05-01

    Parkinson's disease (PD) is a progressive disorder characterized by the emergence of motor deficits. In light of the voluminous and conflicting findings in the literature, the aim of the present quantitative review was to examine the effects of repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex (M1) in the treatment of motor signs in PD. Studies meeting inclusion criteria were analyzed using meta-analytic techniques and the Unified Parkinson's Disease Rating Scale (UPDRS) sections II and III were used as outcome measures. In order to determine the treatment effects of rTMS, the UPDRS II and III scores obtained at baseline, same day, to 1 day post rTMS treatment (short-term follow-up) and 1-month post stimulation (long-term follow-up) were compared between the active and sham rTMS groups. Additionally, the placebo effect was evaluated as the changes in UPDRS III scores in the sham rTMS groups. A placebo effect was not demonstrated, because sham rTMS did not improve motor signs as measured by UPDRS III. Compared with sham rTMS, active rTMS targeting the M1 significantly improved UPDRS III scores at the short-term follow-up (Cohen's d of 0.27, UPDRS III score improvement of 3.8 points). When the long-term follow-up UPDRS III scores were compared with baseline scores, the standardized effect size between active and sham rTMS did not reach significance. However, this translated into a significant nonstandardized 6.3-point improvement on the UPDRS III. No significant improvement in the UPDRS II was found. rTMS over the M1 may improve motor signs. Further studies are needed to provide a definite conclusion.

  9. Distal forelimb representations in primary motor cortex are redistributed after forelimb restriction: a longitudinal study in adult squirrel monkeys.

    PubMed

    Milliken, Garrett W; Plautz, Erik J; Nudo, Randolph J

    2013-03-01

    Primary motor cortex (M1) movement representations reflect acquired motor skills. Representations of muscles and joints used in a skilled task expand. However, it is unknown whether motor restriction in healthy individuals results in complementary reductions in M1 representations. With the use of intracortical microstimulation techniques in squirrel monkeys, detailed maps of movement representations in M1 were derived before and up to 35 wk after restriction of the preferred distal forelimb (DFL) by use of a soft cast. Although total DFL area and movement threshold remained constant, casting resulted in a redistribution of digit and wrist/forearm representations. Digit representations progressively decreased, whereas wrist/forearm representations progressively increased in areal extent. In three of four monkeys, hand preference returned to normal by the end of the postcast recovery period, and postrecovery maps demonstrated reversal of restriction-induced changes. However, in one monkey, a chronic motor impairment occurred in the casted limb. Rehabilitation via a forced-use paradigm resulted in recovery in use and skill of the impaired limb, as well as restoration of normal motor maps. These results demonstrate that plasticity in motor representations can be induced by training or restricting movements of the limb. Physiological changes induced by restriction appear to be reversible, even in the case of adverse motor outcomes. The respective contributions of both disuse and lost motor skills are discussed. These results have relevance for clinical conditions requiring forelimb casting as well as interpreting the differential effects of injury and disuse that are necessarily intertwined after cortical injury, as occurs in stroke.

  10. Distal forelimb representations in primary motor cortex are redistributed after forelimb restriction: a longitudinal study in adult squirrel monkeys

    PubMed Central

    Milliken, Garrett W.; Plautz, Erik J.

    2013-01-01

    Primary motor cortex (M1) movement representations reflect acquired motor skills. Representations of muscles and joints used in a skilled task expand. However, it is unknown whether motor restriction in healthy individuals results in complementary reductions in M1 representations. With the use of intracortical microstimulation techniques in squirrel monkeys, detailed maps of movement representations in M1 were derived before and up to 35 wk after restriction of the preferred distal forelimb (DFL) by use of a soft cast. Although total DFL area and movement threshold remained constant, casting resulted in a redistribution of digit and wrist/forearm representations. Digit representations progressively decreased, whereas wrist/forearm representations progressively increased in areal extent. In three of four monkeys, hand preference returned to normal by the end of the postcast recovery period, and postrecovery maps demonstrated reversal of restriction-induced changes. However, in one monkey, a chronic motor impairment occurred in the casted limb. Rehabilitation via a forced-use paradigm resulted in recovery in use and skill of the impaired limb, as well as restoration of normal motor maps. These results demonstrate that plasticity in motor representations can be induced by training or restricting movements of the limb. Physiological changes induced by restriction appear to be reversible, even in the case of adverse motor outcomes. The respective contributions of both disuse and lost motor skills are discussed. These results have relevance for clinical conditions requiring forelimb casting as well as interpreting the differential effects of injury and disuse that are necessarily intertwined after cortical injury, as occurs in stroke. PMID:23236004

  11. Equilibrium-based movement endpoints elicited from primary motor cortex using repetitive microstimulation.

    PubMed

    Van Acker, Gustaf M; Amundsen, Sommer L; Messamore, William G; Zhang, Hongyu Y; Luchies, Carl W; Cheney, Paul D

    2014-11-19

    High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) is increasingly being used to deduce how the brain encodes coordinated muscle activity and movement. However, the full movement repertoire that can be elicited from the forelimb representation of primary motor cortex (M1) using this method has not been systematically determined. Our goal was to acquire a comprehensive M1 forelimb representational map of movement endpoints elicited with HFLD-ICMS, using stimulus parameters optimal for evoking stable forelimb spatial endpoints. The data reveal a 3D forelimb movement endpoint workspace that is represented in a patchwork fashion on the 2D M1 cortical surface. Although cortical maps of movement endpoints appear quite disorderly with respect to movement space, we show that the endpoint locations in the workspace evoked with HFLD-ICMS of two adjacent cortical points are closer together than would be expected if the organization were random. Although there were few obvious consistencies in the endpoint maps across the two monkeys tested, one notable exception was endpoints bringing the hand to the mouth, which was located at the boundary between the hand and face representation. Endpoints at the extremes of the monkey's workspace and locations above the head were largely absent. Our movement endpoints are best explained as resulting from coactivation of agonist and antagonist muscles driving the joints toward equilibrium positions determined by the length-tension relationships of the muscles. Copyright © 2014 the authors 0270-6474/14/3415722-13$15.00/0.

  12. Primary motor cortex of the parkinsonian monkey: altered neuronal responses to muscle stretch

    PubMed Central

    Pasquereau, Benjamin; Turner, Robert S.

    2013-01-01

    Exaggeration of the long-latency stretch reflex (LLSR) is a characteristic neurophysiologic feature of Parkinson's disease (PD) that contributes to parkinsonian rigidity. To explore one frequently-hypothesized mechanism, we studied the effects of fast muscle stretches on neuronal activity in the macaque primary motor cortex (M1) before and after the induction of parkinsonism by unilateral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We compared results from the general population of M1 neurons and two antidromically-identified subpopulations: distant-projecting pyramidal-tract type neurons (PTNs) and intra-telecenphalic-type corticostriatal neurons (CSNs). Rapid rotations of elbow or wrist joints evoked short-latency responses in 62% of arm-related M1 neurons. As in PD, the late electromyographic responses that constitute the LLSR were enhanced following MPTP. This was accompanied by a shortening of M1 neuronal response latencies and a degradation of directional selectivity, but surprisingly, no increase in single unit response magnitudes. The results suggest that parkinsonism alters the timing and specificity of M1 responses to muscle stretch. Observation of an exaggerated LLSR with no change in the magnitude of proprioceptive responses in M1 is consistent with the idea that the increase in LLSR gain that contributes to parkinsonian rigidity is localized to the spinal cord. PMID:24324412

  13. Biological factors and age-dependence of primary motor cortex experimental plasticity.

    PubMed

    Polimanti, Renato; Simonelli, Ilaria; Zappasodi, Filippo; Ventriglia, Mariacarla; Pellicciari, Maria Concetta; Benussi, Luisa; Squitti, Rosanna; Rossini, Paolo Maria; Tecchio, Franca

    2016-02-01

    To evaluate whether the age-dependence of brain plasticity correlates with the levels of proteins involved in hormone and brain functions we executed a paired associative stimulation (PAS) protocol and blood tests. We measured the PAS-induced plasticity in the primary motor cortex. Blood levels of the brain-derived neurotrophic factor (BDNF), estradiol, the insulin-like growth factor (IGF)-1, the insulin-like growth factor binding protein (IGFBP)-3, progesterone, sex hormone-binding globulin (SHBG), testosterone, and the transforming growth factor beta 1 (TGF-β1) were determined in 15 healthy men and 20 healthy women. We observed an age-related reduction of PAS-induced plasticity in females that it is not present in males. In females, PAS-induced plasticity displayed a correlation with testosterone (p = 0.006) that became a trend after the adjustment for the age effect (p = 0.078). In males, IGF-1 showed a nominally significant correlation with the PAS-induced plasticity (p = 0.043). In conclusion, we observed that hormone blood levels (testosterone in females and IGF-1 in males) may be involved in the age-dependence of brain plasticity.

  14. Median nerve stimulation modulates extracellular signals in the primary motor area of a macaque monkey.

    PubMed

    Papazachariadis, Odysseas; Dante, Vittorio; Ferraina, Stefano

    2013-08-29

    Aiming to better define the functional influence of somatosensory stimuli on the primary motor cortex (M1) of primates, we investigated changes in extracellular neural activity induced by repetitive median nerve stimulation (MNS). We described neural adaptation and signal integration in both the multiunit activity (MUA) and the local field potential (LFP). To identify integration of initial M1 activity in the MNS response, we tested the correlation between peak amplitude responses and band energy preceding the peaks. Most of the sites studied in the M1 resulted responsive to MNS. MUA response peak amplitude decreased significantly in time in all sites during repetitive MNS, LFP response peak amplitude instead resulted more variable. Similarly, correlation analysis with the initial activity revealed a significant influence when tested using MUA peak amplitude modulation and a less significant correlation when tested using LFP peak amplitude. Our findings improve current knowledge on mechanisms underlying early M1 changes consequent to afferent somatosensory stimuli. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Equilibrium-Based Movement Endpoints Elicited from Primary Motor Cortex Using Repetitive Microstimulation

    PubMed Central

    Van Acker, Gustaf M.; Amundsen, Sommer L.; Messamore, William G.; Zhang, Hongyu Y.; Luchies, Carl W.

    2014-01-01

    High-frequency, long-duration intracortical microstimulation (HFLD-ICMS) is increasingly being used to deduce how the brain encodes coordinated muscle activity and movement. However, the full movement repertoire that can be elicited from the forelimb representation of primary motor cortex (M1) using this method has not been systematically determined. Our goal was to acquire a comprehensive M1 forelimb representational map of movement endpoints elicited with HFLD-ICMS, using stimulus parameters optimal for evoking stable forelimb spatial endpoints. The data reveal a 3D forelimb movement endpoint workspace that is represented in a patchwork fashion on the 2D M1 cortical surface. Although cortical maps of movement endpoints appear quite disorderly with respect to movement space, we show that the endpoint locations in the workspace evoked with HFLD-ICMS of two adjacent cortical points are closer together than would be expected if the organization were random. Although there were few obvious consistencies in the endpoint maps across the two monkeys tested, one notable exception was endpoints bringing the hand to the mouth, which was located at the boundary between the hand and face representation. Endpoints at the extremes of the monkey's workspace and locations above the head were largely absent. Our movement endpoints are best explained as resulting from coactivation of agonist and antagonist muscles driving the joints toward equilibrium positions determined by the length–tension relationships of the muscles. PMID:25411500

  16. Role of the primary motor cortex in the maintenance and treatment of pain in fibromyalgia.

    PubMed

    Castillo Saavedra, Laura; Mendonca, Mariana; Fregni, Felipe

    2014-09-01

    Fibromyalgia is a highly prevalent, debilitating disease, characterized by chronic widespread pain. The mechanisms underlying pain are not completely understood, but it is believed to be associated with important neuroplastic changes in pain-related neural circuits. Although the involvement of the pain matrix in fibromyalgia is well established, another area that has been found to play a role in the maintenance and treatment of chronic pain is the primary motor cortex (M1). Maladaptive plasticity of M1 is a common finding in patients with chronic pain and many studies in animal models and in human subjects have shown that modulation of the activity of this cortical area induces significant analgesic effects. Furthermore, studies in other chronic pain syndromes have found alterations in baseline characteristics of M1, including an increase in cortical excitability and an abnormally enhanced response to incoming sensory stimuli. Given these findings, we hypothesize that M1 is a major modulator of pain in fibromyalgia and therefore its baseline activity reflects this strong feedback between M1 and pain-related neural areas. However, the feedback loop between M1 and the pain matrix is not enough to decrease pain in fibromyalgia per se, thus increasing its modulatory effect by engaging this network through different behavioral and modulatory techniques is a potentially beneficial treatment for pain in fibromyalgia.

  17. Prediction of hand trajectory from electrocorticography signals in primary motor cortex.

    PubMed

    Chen, Chao; Shin, Duk; Watanabe, Hidenori; Nakanishi, Yasuhiko; Kambara, Hiroyuki; Yoshimura, Natsue; Nambu, Atsushi; Isa, Tadashi; Nishimura, Yukio; Koike, Yasuharu

    2013-01-01

    Due to their potential as a control modality in brain-machine interfaces, electrocorticography (ECoG) has received much focus in recent years. Studies using ECoG have come out with success in such endeavors as classification of arm movements and natural grasp types, regression of arm trajectories in two and three dimensions, estimation of muscle activity time series and so on. However, there still remains considerable work to be done before a high performance ECoG-based neural prosthetic can be realized. In this study, we proposed an algorithm to decode hand trajectory from 15 and 32 channel ECoG signals recorded from primary motor cortex (M1) in two primates. To determine the most effective areas for prediction, we applied two electrode selection methods, one based on position relative to the central sulcus (CS) and another based on the electrodes' individual prediction performance. The best coefficients of determination for decoding hand trajectory in the two monkeys were 0.4815 ± 0.0167 and 0.7780 ± 0.0164. Performance results from individual ECoG electrodes showed that those with higher performance were concentrated at the lateral areas and areas close to the CS. The results of prediction according with different numbers of electrodes based on proposed methods were also shown and discussed. These results also suggest that superior decoding performance can be achieved from a group of effective ECoG signals rather than an entire ECoG array.

  18. Establishment of a primary culture method for mouse intestinal epithelial cells by organ culture of fetal small intestine.

    PubMed

    Yamada, Kiyoshi; Sato, Kanako; Morishita, Satoru; Kaminogawa, Shuichi; Totsuka, Mamoru

    2009-08-01

    Studies of the physiological functions of intestinal epithelial cells (IECs) have been limited by the difficulty of primary culture of IEC. We established a method for primary culture of mouse IEC by culturing fragments of fetal small intestines pretreated with EDTA. This method reproducibly resulted in the expansion of cytokeratin-positive epithelial cells, and vigorous expansion of the epithelial cells was observed only from intestinal fragments of embryonic days 15-16. These cells expressed alkaline phosphatase activity and major histocompatibility complex (MHC) class II molecules, indicating the mature phenotype of IEC in a small intestine. The cells also presented antigens to CD4(+) T cells. Furthermore, the cells expressed various cytokines and chemokines, and the expression was enhanced by bacterial stimulation. These results indicate that the primary-cultured mouse IEC prepared by the method established here can be a beneficial tool in study of the functions of IECs, especially in mucosal immunity.

  19. Effects of Healthy Ageing on Activation Pattern within the Primary Motor Cortex during Movement and Motor Imagery: An fMRI Study

    PubMed Central

    Sharma, Nikhil; Baron, Jean-Claude

    2014-01-01

    The increase in older adults over the coming decades will be accompanied by a greater burden of chronic neurological diseases affecting the motor system. The motor system adapts to maintain motor performance with the primary motor cortex (BA4) emerging as a pivotal node within this neuroplastic process. Studies of ageing often consider BA4 a homogenous area but cytoarchitectonic studies have revealed two subdivisions, an anterior (BA4a) and posterior subdivision (BA4p). Here we focus upon the effects of ageing on the involvement of BA4a and BA4p during movement and motor imagery (MI). Thirty-one right-handed healthy volunteers were recruited and screened for their ability to perform imagery (5 subjects excluded). The sample was split into an older group (n = 13, mean age 56.4 SD 9.4) and a younger group (n = 13, mean age 27.4 SD 5.3). We used an fMRI block-design (auditory-paced [1 Hz] right hand finger-thumb opposition sequence [2,3,4,5, 2…]) with MI & rest and actual movement & rest. We explored the distribution-based clustering and weighted laterality index within BA4a and BA4p. The involvement of BA4p during MI (measured with distribution-based clustering) was significantly greater in the older group (p<0.05) than in the younger group. Hemispheric balance of BA4p decreased with age during MI (Spearman rho −0.371; p<0.05), whereas that of BA4a decreased with age during actual movement (Spearman rho = −0.458 p<0.01). Irrespective of age, we found BA4 is involved during motor imagery, strengthening the rationale for its potential use in older subjects. These findings suggest that the functions of the subdivisions of BA4 are differentially affected by ageing and have implications regarding how ageing affects the cognitive processes underlying motor functions. PMID:24887402

  20. Cultural democracy: the way forward for primary care of hard to reach New Zealanders.

    PubMed

    Finau, Sitaleki A; Finau, Eseta

    2007-09-01

    The use of cultural democracy, the freedom to practice one's culture without fear, as a framework for primary care service provision is essential for improved health service in a multi cultural society like New Zealand. It is an effective approach to attaining health equity for all. Many successful health ventures are ethnic specific and have gone past cultural competency to the practice of cultural democracy. That is, the services are freely taking on the realities of clients without and malice from those of other ethnicities. In New Zealand the scientific health service to improve the health of a multi cultural society are available but there is a need to improve access and utilization by hard to reach New Zealanders. This paper discusses cultural democracy and provide example of how successful health ventures that had embraced cultural democracy were implemented. It suggests that cultural democracy will provide the intellectual impetus and robust philosophy for moving from equality to equity in health service access and utilization. This paper would provide a way forward to improved primary care utilization, efficiency, effectiveness and equitable access especially for the hard to reach populations. use the realities of Pacificans in New Zealand illustrate the use of cultural democracy, and thus equity to address the "inverse care law" of New Zealand. The desire is for primary care providers to take cognizance and use cultural democracy and equity as the basis for the design and practice of primary health care for the hard to reach New Zealanders.

  1. Short-term and long-term plasticity interaction in human primary motor cortex.

    PubMed

    Iezzi, Ennio; Suppa, Antonio; Conte, Antonella; Li Voti, Pietro; Bologna, Matteo; Berardelli, Alfredo

    2011-05-01

    Repetitive transcranial magnetic stimulation (rTMS) over primary motor cortex (M1) elicits changes in motor evoked potential (MEP) size thought to reflect short- and long-term forms of synaptic plasticity, resembling short-term potentiation (STP) and long-term potentiation/depression (LTP/LTD) observed in animal experiments. We designed this study in healthy humans to investigate whether STP as elicited by 5-Hz rTMS interferes with LTP/LTD-like plasticity induced by intermittent and continuous theta-burst stimulation (iTBS and cTBS). The effects induced by 5-Hz rTMS and iTBS/cTBS were indexed as changes in MEP size. We separately evaluated changes induced by 5-Hz rTMS, iTBS and cTBS applied alone and those induced by iTBS and cTBS delivered after priming 5-Hz rTMS. Interactions between 5-Hz rTMS and iTBS/cTBS were investigated under several experimental conditions by delivering 5-Hz rTMS at suprathreshold and subthreshold intensity, allowing 1 and 5 min intervals to elapse between 5-Hz rTMS and TBS, and delivering one and ten 5-Hz rTMS trains. We also investigated whether 5-Hz rTMS induces changes in intracortical excitability tested with paired-pulse transcranial magnetic stimulation. When given alone, 5-Hz rTMS induced short-lasting and iTBS/cTBS induced long-lasting changes in MEP amplitudes. When M1 was primed with 10 suprathreshold 5-Hz rTMS trains at 1 min before iTBS or cTBS, the iTBS/cTBS-induced after-effects disappeared. The 5-Hz rTMS left intracortical excitability unchanged. We suggest that STP elicited by suprathreshold 5-Hz rTMS abolishes iTBS/cTBS-induced LTP/LTD-like plasticity through non-homeostatic metaplasticity mechanisms. Our study provides new information on interactions between short-term and long-term rTMS-induced plasticity in human M1.

  2. Transient inhibition of primary motor cortex suppresses hand muscle responses during a reactive reach to grasp.

    PubMed

    Bolton, David A E; Patel, Rupesh; Staines, W Richard; McIlroy, William E

    2011-10-24

    Rapid balance reactions such as compensatory reach to grasp represent important response strategies following unexpected loss of balance. While it has been assumed that early corrective actions arise from subcortical networks, recent research has prompted speculation about the potential role of cortical involvement. With reach to grasp reactions there is evidence of parallels in the control of perturbation-evoked reaching versus rapid voluntary reaching. However, the potential role of cortical involvement in such rapid balance reactions remains speculative. To test if cortical motor regions are involved we used continuous theta burst stimulation (cTBS) to temporarily suppress the hand area of primary motor cortex (M1) in participants involved in two reaching conditions: (1) rapid compensatory perturbation-evoked reach to grasp and (2) voluntary reach to grasp in response to an auditory cue. We hypothesized that following cTBS to the left M1 hand area we would find diminished EMG responses in the reaching (right) hand for both compensatory and voluntary movements. To isolate balance reactions to the upper limb participants were seated in an elevated tilt-chair with a stable handle positioned in front of their right shoulder. The chair was held vertical by a magnet and triggered to fall backward randomly. To regain balance, participants were instructed to reach for the handle as quickly as possible with the right hand upon chair release. Intermixed with perturbation trials, participants were also required to reach for the same handle but in response to an auditory tone. Muscle activity was recorded from several muscles of the right arm/hand using electromyography. As expected, movement time and muscle onsets were much faster following perturbation versus auditory-cued reaching. The novel finding from our study was the reduced amplitude of hand muscle activity post-cTBS for both perturbation-cued and auditory-cued reaches. Moreover, this reduction was specific to the

  3. Hand preference for tool-use in capuchin monkeys (Cebus apella) is associated with asymmetry of the primary motor cortex.

    PubMed

    Phillips, Kimberley A; Thompson, Claudia R

    2013-05-01

    Skilled motor actions are associated with handedness and neuroanatomical specializations in humans. Recent reports have documented similar neuroanatomical asymmetries and their relationship to hand preference in some nonhuman primate species, including chimpanzees and capuchin monkeys. We investigated whether capuchins displayed significant hand preferences for a tool-use task and whether such preferences were associated with motor-processing regions of the brain. Handedness data on a dipping tool-use task and high-resolution 3T MRI scans were collected from 15 monkeys. Capuchins displayed a significant group-level left-hand preference for this type of tool use, and handedness was associated with asymmetry of the primary motor cortex. Left-hand preferent individuals displayed a deeper central sulcus in the right hemisphere. Our results suggest that capuchins show an underlying right-hemisphere bias for skilled movement.

  4. Hand Preference for Tool-Use in Capuchin Monkeys (Cebus apella) is Associated with Asymmetry of the Primary Motor Cortex

    PubMed Central

    Phillips, Kimberley A.; Thompson, Claudia R.

    2012-01-01

    Skilled motor actions are associated with handedness and neuroanatomical specializations in humans. Recent reports have documented similar neuroanatomical asymmetries and their relationship to hand preference in some nonhuman primate species, including chimpanzees and capuchin monkeys. We investigated whether capuchins displayed significant hand preferences for a tool use task and whether such preferences were associated with motor-processing regions of the brain. Handedness data on a dipping tool-use task and high-resolution 3T MRI scans were collected from 15 monkeys. Capuchins displayed a significant group-level left-hand preference for this type of tool use, and handedness was associated with asymmetry of the primary motor cortex. Left-hand preferent individuals displayed a deeper central sulcus in the right hemisphere. Our results suggest that capuchins show an underlying right-hemisphere bias for skilled movement. PMID:22987442

  5. Primary Spinal OPC Culture System from Adult Zebrafish to Study Oligodendrocyte Differentiation In Vitro

    PubMed Central

    Kroehne, Volker; Tsata, Vasiliki; Marrone, Lara; Froeb, Claudia; Reinhardt, Susanne; Gompf, Anne; Dahl, Andreas; Sterneckert, Jared; Reimer, Michell M.

    2017-01-01

    Endogenous oligodendrocyte progenitor cells (OPCs) are a promising target to improve functional recovery after spinal cord injury (SCI) by remyelinating denuded, and therefore vulnerable, axons. Demyelination is the result of a primary insult and secondary injury, leading to conduction blocks and long-term degeneration of the axons, which subsequently can lead to the loss of their neurons. In response to SCI, dormant OPCs can be activated and subsequently start to proliferate and differentiate into mature myelinating oligodendrocytes (OLs). Therefore, researchers strive to control OPC responses, and utilize small molecule screening approaches in order to identify mechanisms of OPC activation, proliferation, migration and differentiation. In zebrafish, OPCs remyelinate axons of the optic tract after lysophosphatidylcholine (LPC)-induced demyelination back to full thickness myelin sheaths. In contrast to zebrafish, mammalian OPCs are highly vulnerable to excitotoxic stress, a cause of secondary injury, and remyelination remains insufficient. Generally, injury induced remyelination leads to shorter internodes and thinner myelin sheaths in mammals. In this study, we show that myelin sheaths are lost early after a complete spinal transection injury, but are re-established within 14 days after lesion. We introduce a novel, easy-to-use, inexpensive and highly reproducible OPC culture system based on dormant spinal OPCs from adult zebrafish that enables in vitro analysis. Zebrafish OPCs are robust, can easily be purified with high viability and taken into cell culture. This method enables to examine why zebrafish OPCs remyelinate better than their mammalian counterparts, identify cell intrinsic responses, which could lead to pro-proliferating or pro-differentiating strategies, and to test small molecule approaches. In this methodology paper, we show efficient isolation of OPCs from adult zebrafish spinal cord and describe culture conditions that enable analysis up to 10

  6. Pericellular oxygen concentration of cultured primary human trophoblasts

    PubMed Central

    Chen, Baosheng; Longtine, Mark S.; Nelson, D. Michael

    2012-01-01

    Introduction Oxygen is pivotal in placental development and function. In vitro culture of human trophoblasts provides a useful model to study this phenomenon, but a hotly debated issue is whether or not the oxygen tension of the culture conditions mimics in vivo conditions. We tested the hypothesis that ambient oxygen tensions in culture reflect the pericellular oxygen levels. Methods We used a microelectrode oxygen sensor to measure the concentration of dissolved oxygen in the culture medium equilibrated with 21%, 8% or <0.5% oxygen. Results The concentration of oxygen in medium without cells resembled that in the ambient atmosphere. The oxygen concentration present in medium bathing trophoblasts was remarkably dependent on the depth within the medium where sampling occurred, and the oxygen concentration within the overlying atmosphere was not reflected in medium immediately adjacent to the cells. Indeed, the pericellular oxygen concentration was in a range that most would consider severe hypoxia, at ≤ 0.6% oxygen or about 4.6 mm Hg, when the overlying atmosphere was 21% oxygen. Conclusions We conclude that culture conditions of 21% oxygen are unable to replicate the pO2 of 40–60 mm Hg commonly attributed to the maternal blood in the intervillous space in the second and third trimesters of pregnancy. We further surmise that oxygen atmospheres in culture conditions between 0.5% and 21% provide different oxygen fluxes in the immediate pericellular environment yet can still yield insights into the responses of human trophoblast to different oxygen conditions. PMID:23211472

  7. A meta-ethnography of organisational culture in primary care medical practice.

    PubMed

    Grant, Suzanne; Guthrie, Bruce; Entwistle, Vikki; Williams, Brian

    2014-01-01

    Over the past decade, there has been growing international interest in shaping local organisational cultures in primary healthcare. However, the contextual relevance of extant culture assessment instruments to the primary care context has been questioned. The aim of this paper is to derive a new contextually appropriate understanding of the key dimensions of primary care medical practice organisational culture and their inter-relationship through a synthesis of published qualitative research. A systematic search of six electronic databases followed by a synthesis using techniques of meta-ethnography involving translation and re-interpretation. A total of 16 papers were included in the meta-ethnography from the UK, the USA, Canada, Australia and New Zealand that fell into two related groups: those focused on practice organisational characteristics and narratives of practice individuality; and those focused on sub-practice variation across professional, managerial and administrative lines. It was found that primary care organisational culture was characterised by four key dimensions, i.e. responsiveness, team hierarchy, care philosophy and communication. These dimensions are multi-level and inter-professional in nature, spanning both practice and sub-practice levels. The research contributes to organisational culture theory development. The four new cultural dimensions provide a synthesized conceptual framework for researchers to evaluate and understand primary care cultural and sub-cultural levels. The synthesised cultural dimensions present a framework for practitioners to understand and change organisational culture in primary care teams. The research uses an innovative research methodology to synthesise the existing qualitative research and is one of the first to develop systematically a qualitative conceptual framing of primary care organisational culture.

  8. Enhanced auditory evoked activity to self-generated sounds is mediated by primary and supplementary motor cortices.

    PubMed

    Reznik, Daniel; Ossmy, Ori; Mukamel, Roy

    2015-02-04

    Accumulating evidence demonstrates that responses in auditory cortex to auditory consequences of self-generated actions are modified relative to the responses evoked by identical sounds generated by an external source. Such modifications have been suggested to occur through a corollary discharge sent from the motor system, although the exact neuroanatomical origin is unknown. Furthermore, since tactile input has also been shown to modify responses in auditory cortex, it is not even clear whether the source of such modifications is motor output or somatosensory feedback. We recorded functional magnetic resonance imaging (fMRI) data from healthy human subjects (n = 11) while manipulating the rate at which they performed sound-producing actions with their right hand. In addition, we manipulated the amount of tactile feedback to examine the relative roles of motor and somatosensory cortices in modifying evoked activity in auditory cortex (superior temporal gyrus). We found an enhanced fMRI signal in left auditory cortex during perception of self-generated sounds relative to passive listening to identical sounds. Moreover, the signal difference between active and passive conditions in left auditory cortex covaried with the rate of sound-producing actions and was invariant to the amount of tactile feedback. Together with functional connectivity analysis, our results suggest motor output from supplementary motor area and left primary motor cortex as the source of signal modification in auditory cortex during perception of self-generated sounds. Motor signals from these regions could represent a predictive signal of the expected auditory consequences of the performed action.

  9. Afferent-induced facilitation of primary motor cortex excitability in the region controlling hand muscles in humans.

    PubMed

    Devanne, H; Degardin, A; Tyvaert, L; Bocquillon, P; Houdayer, E; Manceaux, A; Derambure, P; Cassim, F

    2009-08-01

    Sensory inputs from cutaneous and limb receptors are known to influence motor cortex network excitability. Although most recent studies have focused on the inhibitory influences of afferent inputs on arm motor responses evoked by transcranial magnetic stimulation (TMS), facilitatory effects are rarely considered. In the present work, we sought to establish how proprioceptive sensory inputs modulate the excitability of the primary motor cortex region controlling certain hand and wrist muscles. Suprathreshold TMS pulses were preceded either by median nerve stimulation (MNS) or index finger stimulation with interstimulus intervals (ISIs) ranging from 20 to 200 ms (with particular focus on 40-80 ms). Motor-evoked potentials recorded in the abductor pollicis brevis (APB), first dorsalis interosseus and extensor carpi radialis muscles were strongly facilitated (by up to 150%) by MNS with ISIs of around 60 ms, whereas digit stimulation had only a weak effect. When MNS was delivered at the interval that evoked the optimal facilitatory effect, the H-reflex amplitude remained unchanged and APB motor responses evoked with transcranial electric stimulation were not increased as compared with TMS. Afferent-induced facilitation and short-latency intracortical inhibition (SICI) and intracortical facilitation (ICF) mechanisms are likely to interact in cortical circuits, as suggested by the strong facilitation observed when MNS was delivered concurrently with ICF and the reduction of SICI following MNS. We conclude that afferent-induced facilitation is a mechanism which probably involves muscle spindle afferents and should be considered when studying sensorimotor integration mechanisms in healthy and disease situations.

  10. An improvement in perception of self-generated tactile stimuli following theta-burst stimulation of primary motor cortex

    PubMed Central

    Voss, Martin; Bays, Paul M.; Rothwell, John C.; Wolpert, Daniel M.

    2007-01-01

    Recent studies have shown that self-generated tactile sensations are perceived as weaker than the same sensations externally generated. This has been linked to a central comparator mechanism that uses efference copy to attenuate the predictable component of sensory inputs arising from one's own actions in order to enhance the salience of external stimuli. To provide a quantitative measure of this attenuation, a force-matching task was developed in which subjects experience a force applied to their finger and are then required to match the perceived force by actively pushing on the finger using their other hand. The attenuation of predictable sensory input results in subjects producing a larger active force than was experienced passively. Here, we have examined the effects of a novel rTMS protocol, theta-burst stimulation (TBS), over primary motor cortex on this attenuation. TBS can alter the excitability of motor cortex to incoming activity. We show that application of a 20 s continuous train of TBS, that depresses motor cortex, significantly improves performance in a force-matching task. This suggests that the TBS intervention disturbed the predictive process that uses efference copy signals to attenuate predictable sensory input. A possible explanation for the effect is that TBS has a differential effect on the populations of neurones that generate motor output in M1 than on those neural structures that are involved in generating an efference copy of the motor command. PMID:17560617

  11. Primary motor cortex alterations in Alzheimer disease: A study in the 3xTg-AD model.

    PubMed

    Orta-Salazar, E; Feria-Velasco, A I; Díaz-Cintra, S

    2017-04-19

    In humans and animal models, Alzheimer disease (AD) is characterised by accumulation of amyloid-β peptide (Aβ) and hyperphosphorylated tau protein, neuronal degeneration, and astrocytic gliosis, especially in vulnerable brain regions (hippocampus and cortex). These alterations are associated with cognitive impairment (loss of memory) and non-cognitive impairment (motor impairment). The purpose of this study was to identify cell changes (neurons and glial cells) and aggregation of Aβ and hyperphosphorylated tau protein in the primary motor cortex (M1) in 3xTg-AD mouse models at an intermediate stage of AD. We used female 3xTg-AD mice aged 11 months and compared them to non-transgenic mice of the same age. In both groups, we assessed motor performance (open field test) and neuronal damage in M1 using specific markers: BAM10 (extracellular Aβ aggregates), tau 499 (hyperphosphorylated tau protein), GFAP (astrocytes), and Klüver-Barrera staining (neurons). Female 3xTg-AD mice in intermediate stages of the disease displayed motor and cellular alterations associated with Aβ and hyperphosphorylated tau protein deposition in M1. Patients with AD display signs and symptoms of functional impairment from early stages. According to our results, M1 cell damage in intermediate-stage AD affects motor function, which is linked to progression of the disease. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Assessment of Fine-Motor Development of Primary Students with Informal Medical Tests.

    ERIC Educational Resources Information Center

    Traynelis-Yurek, Elaine; Strong, Mary W.

    This study examined whether informal medical assessments could be used by classroom teachers to assess fine-motor ability and if there is any connection between fine-motor ability and reading achievement. Subjects were 174 half-day kindergarten children from whole-language classrooms in three states. Subjects were pretested in October and…

  13. Sensory-motor interactions for vocal pitch monitoring in non-primary human auditory cortex.

    PubMed

    Greenlee, Jeremy D W; Behroozmand, Roozbeh; Larson, Charles R; Jackson, Adam W; Chen, Fangxiang; Hansen, Daniel R; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A

    2013-01-01

    The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (-100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70-150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control.

  14. Role of the primary motor and sensory cortex in precision grasping: a transcranial magnetic stimulation study.

    PubMed

    Schabrun, S M; Ridding, M C; Miles, T S

    2008-02-01

    Human precision grip requires precise scaling of the grip force to match the weight and frictional conditions of the object. The ability to produce an accurately scaled grip force prior to lifting an object is thought to be the result of an internal feedforward model. However, relatively little is known about the roles of various brain regions in the control of such precision grip-lift synergies. Here we investigate the role of the primary motor (M1) and sensory (S1) cortices during a grip-lift task using inhibitory transcranial magnetic theta-burst stimulation (TBS). Fifteen healthy individuals received 40 s of either (i) M1 TBS, (ii) S1 TBS or (iii) sham stimulation. Following a 5-min rest, subjects lifted a manipulandum five times using a precision grip or completed a simple reaction time task. Following S1 stimulation, the duration of the pre-load phase was significantly longer than following sham stimulation. Following M1 stimulation, the temporal relationship between changes in grip and load force was altered, with changes in grip force coming to lag behind changes in load force. This result contrasts with that seen in the sham condition where changes in grip force preceded changes in load force. No significant difference was observed in the simple reaction task following either M1 or S1 stimulation. These results further quantify the contribution of the M1 to anticipatory grip-force scaling. In addition, they provide the first evidence for the contribution of S1 to object manipulation, suggesting that sensory information is not necessary for optimal functioning of anticipatory control.

  15. Sensory-Motor Interactions for Vocal Pitch Monitoring in Non-Primary Human Auditory Cortex

    PubMed Central

    Larson, Charles R.; Jackson, Adam W.; Chen, Fangxiang; Hansen, Daniel R.; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A.

    2013-01-01

    The neural mechanisms underlying processing of auditory feedback during self-vocalization are poorly understood. One technique used to study the role of auditory feedback involves shifting the pitch of the feedback that a speaker receives, known as pitch-shifted feedback. We utilized a pitch shift self-vocalization and playback paradigm to investigate the underlying neural mechanisms of audio-vocal interaction. High-resolution electrocorticography (ECoG) signals were recorded directly from auditory cortex of 10 human subjects while they vocalized and received brief downward (−100 cents) pitch perturbations in their voice auditory feedback (speaking task). ECoG was also recorded when subjects passively listened to playback of their own pitch-shifted vocalizations. Feedback pitch perturbations elicited average evoked potential (AEP) and event-related band power (ERBP) responses, primarily in the high gamma (70–150 Hz) range, in focal areas of non-primary auditory cortex on superior temporal gyrus (STG). The AEPs and high gamma responses were both modulated by speaking compared with playback in a subset of STG contacts. From these contacts, a majority showed significant enhancement of high gamma power and AEP responses during speaking while the remaining contacts showed attenuated response amplitudes. The speaking-induced enhancement effect suggests that engaging the vocal motor system can modulate auditory cortical processing of self-produced sounds in such a way as to increase neural sensitivity for feedback pitch error detection. It is likely that mechanisms such as efference copies may be involved in this process, and modulation of AEP and high gamma responses imply that such modulatory effects may affect different cortical generators within distinctive functional networks that drive voice production and control. PMID:23577157

  16. An Air-Liquid Interface Culture System for 3D Organoid Culture of Diverse Primary Gastrointestinal Tissues.

    PubMed

    Li, Xingnan; Ootani, Akifumi; Kuo, Calvin

    2016-01-01

    Conventional in vitro analysis of gastrointestinal epithelium usually relies on two-dimensional (2D) culture of epithelial cell lines as monolayer on impermeable surfaces. However, the lack of context of differentiation and tissue architecture in 2D culture can hinder the faithful recapitulation of the phenotypic and morphological characteristics of native epithelium. Here, we describe a robust long-term three-dimensional (3D) culture methodology for gastrointestinal culture, which incorporates both epithelial and mesenchymal/stromal components into a collagen-based air-liquid interface 3D culture system. This system allows vigorously expansion of primary gastrointestinal epithelium for over 60 days as organoids with both proliferation and multilineage differentiation, indicating successful long-term intestinal culture within a microenvironment accurately recapitulating the stem cell niche.

  17. Transformation of adult rat cardiac myocytes in primary culture.

    PubMed

    Banyasz, Tamas; Lozinskiy, Ilya; Payne, Charles E; Edelmann, Stephanie; Norton, Byron; Chen, Biyi; Chen-Izu, Ye; Izu, Leighton T; Balke, C William

    2008-03-01

    We characterized the morphological, electrical and mechanical alterations of cardiomyocytes in long-term cell culture. Morphometric parameters, sarcomere length, T-tubule density, cell capacitance, L-type calcium current (I(Ca,L)), inward rectifier potassium current (I(K1)), cytosolic calcium transients, action potential and contractile parameters of adult rat ventricular myocytes were determined on each day of 5 days in culture. We also analysed the health of the myocytes using an apoptotic/necrotic viability assay. The data show that myocytes undergo profound morphological and functional changes during culture. We observed a progressive reduction in the cell area (from 2502 +/- 70 microm(2) on day 0 to 1432 +/- 50 microm(2) on day 5), T-tubule density, systolic shortening (from 0.11 +/- 0.02 to 0.05 +/- 0.01 microm) and amplitude of calcium transients (from 1.54 +/- 0.19 to 0.67 +/- 0.19) over 5 days of culture. The negative force-frequency relationship, characteristic of rat myocardium, was maintained during the first 2 days but diminished thereafter. Cell capacitance (from 156 +/- 8 to 105 +/- 11 pF) and membrane currents were also reduced (I(Ca,L), from 3.98 +/- 0.39 to 2.12 +/- 0.37 pA pF; and I(K1), from 34.34p +/- 2.31 to 18.00 +/- 5.97 pA pF(-1)). We observed progressive depolarization of the resting membrane potential during culture (from 77.3 +/- 2.5 to 34.2 +/- 5.9 mV) and, consequently, action potential morphology was profoundly altered as well. The results of the viability assays indicate that these alterations could not be attributed to either apoptosis or necrosis but are rather an adaptation to the culture conditions over time.

  18. Homophobia, Transphobia and Culture: Deconstructing Heteronormativity in English Primary Schools

    ERIC Educational Resources Information Center

    DePalma, Renee; Jennett, Mark

    2010-01-01

    This article presents some of the advances in legal support for addressing homophobia and transphobia in school settings and provides a critique of school-based policies that focus on these phenomena as particular incidents involving bullies and victims. Defining heteronormativity as a cultural phenomenon underpinning recognisable acts of…

  19. Homophobia, Transphobia and Culture: Deconstructing Heteronormativity in English Primary Schools

    ERIC Educational Resources Information Center

    DePalma, Renee; Jennett, Mark

    2010-01-01

    This article presents some of the advances in legal support for addressing homophobia and transphobia in school settings and provides a critique of school-based policies that focus on these phenomena as particular incidents involving bullies and victims. Defining heteronormativity as a cultural phenomenon underpinning recognisable acts of…

  20. Pyrethroid insecticide accumulation in primary cultures of cortical neurons in vitro

    EPA Science Inventory

    Primary cultures of neurons have been widely utilized to study the actions of pyrethroids and other neurotoxicants, with the presumption that the media concentration accurately reflects the dose received by the cells. However, recent studies have demonstrated that lipophilic comp...

  1. Establishing and maintaining primary cell cultures derived from the ctenophore Mnemiopsis leidyi.

    PubMed

    Vandepas, Lauren E; Warren, Kaitlyn J; Amemiya, Chris T; Browne, William E

    2017-04-01

    We have developed an efficient method for the preparation and maintenance of primary cell cultures isolated from adult Mnemiopsis leidyi, a lobate ctenophore. Our primary cell cultures are derived from tissue explants or enzymatically dissociated cells, and maintained in a complex undefined ctenophore mesogleal serum. These methods can be used to isolate, maintain and visually monitor ctenophore cells to assess proliferation, cellular morphology and cell differentiation in future studies. Exemplar cell types that can be easily isolated from primary cultures include proliferative ectodermal and endodermal cells, motile amebocyte-like cells, and giant smooth muscle cells that exhibit inducible contractile properties. We have also derived 'tissue envelopes' containing sections of endodermal canal surrounded by mesoglea and ectoderm that can be used to monitor targeted cell types in an in vivo context. Access to efficient and reliably generated primary cell cultures will facilitate the analysis of ctenophore development, physiology and morphology from a cell biological perspective.

  2. Toward a world-class culture in primary care: listening to the voice of the customer.

    PubMed

    Benson, D S

    1996-01-01

    This article on creating a world-class culture in primary care stresses the importance of customers. The concept of patients as external customers is addressed; the emphasis, however, is on healthcare professionals' responsibilities toward one another as internal customers.

  3. Correction: Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics.

    PubMed

    Colvin, Robert A; Lai, Barry; Holmes, William R; Lee, Daewoo

    2015-09-01

    Correction for 'Understanding metal homeostasis in primary cultured neurons. Studies using single neuron subcellular and quantitative metallomics' by Robert A. Colvin et al., Metallomics, 2015, 7, 1111-1123.

  4. Pyrethroid insecticide accumulation in primary cultures of cortical neurons in vitro

    EPA Science Inventory

    Primary cultures of neurons have been widely utilized to study the actions of pyrethroids and other neurotoxicants, with the presumption that the media concentration accurately reflects the dose received by the cells. However, recent studies have demonstrated that lipophilic comp...

  5. Cartilaginous constructs using primary chondrocytes from continuous expansion culture seeded in dense collagen gels.

    PubMed

    Rosenzweig, D H; Chicatun, F; Nazhat, S N; Quinn, T M

    2013-12-01

    Cell-based therapies such as autologous chondrocyte implantation require in vitro cell expansion. However, standard culture techniques require cell passaging, leading to dedifferentiation into a fibroblast-like cell type. Primary chondrocytes grown on continuously expanding culture dishes (CE culture) limits passaging and protects against dedifferentiation. The authors tested whether CE culture chondrocytes were advantageous for producing mechanically competent cartilage matrix when three-dimensionally seeded in dense collagen gels. Primary chondrocytes, grown either in CE culture or passaged twice on static silicone dishes (SS culture; comparable to standard methods), were seeded in dense collagen gels and cultured for 3 weeks in the absence of exogenous chondrogenic growth factors. Compared with gels seeded with SS culture chondrocytes, CE chondrocyte-seeded gels had significantly higher chondrogenic gene expression after 2 and 3 weeks in culture, correlating with significantly higher aggrecan and type II collagen protein accumulation. There was no obvious difference in glycosaminoglycan content from either culture condition, yet CE chondrocyte-seeded gels were significantly thicker and had a significantly higher dynamic compressive modulus than SS chondrocyte-seeded gels after 3 weeks. Chondrocytes grown in CE culture and seeded in dense collagen gels produce more cartilaginous matrix with superior mechanical properties, making them more suitable than SS cultured cells for tissue engineering applications. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  6. Organizational culture predicts job satisfaction and perceived clinical effectiveness in pediatric primary care practices.

    PubMed

    Brazil, Kevin; Wakefield, Dorothy B; Cloutier, Michelle M; Tennen, Howard; Hall, Charles B

    2010-01-01

    In recent years, there has been a growing understanding that organizational culture is related to an organization's performance. However, few studies have examined organizational culture in medical group practices. The purpose of this study was to examine the relationship of organizational culture on provider job satisfaction and perceived clinical effectiveness in primary care pediatric practices. This cross-sectional study included 36 primary care pediatric practices located in Connecticut. There were 374 participants in this study, which included 127 clinicians and 247 nonclinicians. Office managers completed a questionnaire that recorded staff and practice characteristics; all participants completed the Organizational Culture Scale, a questionnaire that assessed the practice on four cultural domains (i.e., group, developmental, rational, and hierarchical), and the Primary Care Organizational Questionnaire that evaluated perceived effectiveness and job satisfaction. Hierarchical linear models using a restricted maximum likelihood estimation method were used to evaluate whether the practice culture types predicted job satisfaction and perceived effectiveness. Group culture was positively associated with both satisfaction and perceived effectiveness. In contrast, hierarchical and rational culture were negatively associated with both job satisfaction and perceived effectiveness. These relationships were true for clinicians, nonclinicians, and the practice as a whole. Our study demonstrates that practice culture is associated with job satisfaction and perceived clinical effectiveness and that a group culture was associated with high job satisfaction and perceived effectiveness.

  7. Family, Culture and Achievement in the Primary Schools of Botswana.

    ERIC Educational Resources Information Center

    Lynch, Patrick D.

    This paper traces the development of the educational system of Botswana, a small south African country of one million, emphasizing its democratic origins and customs, historical influences, social trends, and economic support. Changes in the educational system, especially in universal primary education, since its independence from Great Britain in…

  8. High-definition transcranial direct current stimulation to both primary motor cortices improves unimanual and bimanual dexterity.

    PubMed

    Pixa, Nils H; Steinberg, Fabian; Doppelmayr, Michael

    2017-03-16

    While most research on brain stimulation with transcranial direct current stimulation (tDCS) targets unimanual motor tasks, little is known about its effects on bimanual motor performance. This study aims to investigate the effects of tDCS on unimanual as well as bimanual motor dexterity. We examined the effects of bihemispheric anodal high-definition tDCS (HD-atDCS) on both primary motor cortices (M1) applied concurrent with unimanual and bimanual motor training. We then measured the effects with the Purdue Pegboard Test (PPT) and compared them to a sham stimulation. Between a pretest and posttest, 31 healthy, right-handed participants practiced the PPT on three consecutive days and received - simultaneous to motor practice - either HD-atDCS over the left and right M1 (STIM, n=16) or a sham stimulation (SHAM, n=15). Five to seven days after the posttest, a follow-up test was conducted. Two-way ANOVAs with repeated measures showed significantly increased performance for all PPT-scores (p<0.001) in both groups. The scores for the right hand, both hands, and overall showed significant TIME x GROUP interactions (p<.05) with more improved performance for the STIM group, while left hand performance was not significantly altered. These effects were most pronounced in the follow-up test. Thus, we can conclude that a bihemispheric HD-atDCS of both M1's improves performance of unimanual and bimanual dexterity. The strength of the effects, however, depends on which hand is used in the unimanual task and the type of bimanual task performed.

  9. The primary locus of motor neuron death in an ALS–PDC mouse model

    PubMed Central

    Lee, Grace; Chu, Tony; Shaw, Christopher A.

    2010-01-01

    A mouse model of amyotrophic lateral sclerosis–parkinsonism–dementia complex based on the consumption of cycad seed flour was used to determine whether the observed pathology of motor neuron loss begins in the distal axons or the spinal cord. Assessments of neuromuscular junction integrity and motor neurons were performed at multiple time points. Mice fed cycad pellets performed worse on the wire hang than controls. Microglial activation in cycad-fed mice was observed with motor neuron degeneration at 12 weeks, but reactive astrocyte proliferation was not observed. After 33 weeks of cycad feeding, motor neuron loss had stabilized, with no evidence of neuromuscular junction endplate denervation. These data suggest that neuronal pathology begins at the soma and proceeds distally in a ‘dying forward’ pattern. PMID:19633581

  10. Adherent Primary Cultures of Mouse Intercostal Muscle Fibers for Isolated Fiber Studies

    PubMed Central

    Robison, Patrick; Hernández-Ochoa, Erick O.; Schneider, Martin F.

    2011-01-01

    Primary culture models of single adult skeletal muscle fibers dissociated from locomotor muscles adhered to glass coverslips are routine and allow monitoring of functional processes in living cultured fibers. To date, such isolated fiber cultures have not been established for respiratory muscles, despite the fact that dysfunction of core respiratory muscles leading to respiratory arrest is the most common cause of death in many muscular diseases. Here we present the first description of an adherent culture system for single adult intercostal muscle fibers from the adult mouse. This system allows for monitoring functional properties of these living muscle fibers in culture with or without electrical field stimulation to drive muscle fiber contraction at physiological or pathological respiratory firing patterns. We also provide initial characterization of these fibers, demonstrating several common techniques in this new model system in the context of the established Flexor Digitorum Brevis muscle primary culture model. PMID:21869860

  11. A Multi-Cultural Interaction through Video Conferencing in Primary Schools

    ERIC Educational Resources Information Center

    Duygu Eristi, Suzan

    2012-01-01

    This study investigated Turkish and Canadian primary school students' ways of expressing their perception of cultural understanding through video conferencing and that of cultural interaction through video conferencing. The qualitative research data were collected in the form of interviews. The results obtained were analyzed and interpreted based…

  12. Creative Partnerships? Cultural Policy and Inclusive Arts Practice in One Primary School

    ERIC Educational Resources Information Center

    Hall, Christine; Thomson, Pat

    2007-01-01

    This article traces the "cultural turn" in UK educational policy through an analysis of the Creative Partnerships policy (New Labour's "flagship programme in the cultural education field") and a consideration of an arts project funded under this initiative in one primary school. It argues that current educational policy…

  13. Contribution to Cultural Organization, Working Motivation and Job Satisfaction on the Performance of Primary School Teacher

    ERIC Educational Resources Information Center

    Murtedjo; Suharningsih

    2016-01-01

    The purposes of this study are: (1) describes the performance of the teacher, organizational culture, work motivation and job satisfaction; (2) determine whether there is a significant direct relationship between organizational culture, work motivation and job satisfaction on the performance of primary school teachers. Through the study of the…

  14. English and French Pedagogical Cultures: Convergence and Divergence in Cameroonian Primary School Teachers' Discourse

    ERIC Educational Resources Information Center

    Esch, Edith

    2012-01-01

    This article approaches the phenomenon of the continuing influence of French and English pedagogical cultures in Africa relying on post-modern notions of time and space. It reports on a project carried out in Cameroon where both cultures are in contact and where the teachers from two primary schools were observed and interviewed over a period of…

  15. Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population

    PubMed Central

    Loci, Lorena; Mitsumoto, Hiroshi; Lomen-Hoerth, Catherine; Kisanuki, Yasushi; Simmons, Zachary; Maragakis, Nicholas J; McVey, April L; Al-Lahham, Tawfiq; Heiman-Patterson, Terry D; Andrews, Jinsy; McDonnell, Erin; Cudkowicz, Merit; Atassi, Nazem

    2015-01-01

    Objectives The goals of this study were to characterize clinical and electrophysiologic findings of subjects with upper motor neuron disease and to explore feasibility of clinical trials in this population. Methods Twenty northeast ALS consortium (NEALS) sites performed chart reviews to identify active clinical pure upper motor neuron disease patients. Patients with hereditary spastic paraplegia (HSP) or meeting revised El Escorial electrodiagnostic criteria for ALS were excluded. Patients were classified into two groups according to the presence or absence of minor electromyography (EMG) abnormalities. Results 233 subjects with upper motor neuron disease were identified; 217 had available EMG data. Normal EMGs were seen in 140 subjects, and 77 had minor denervation. Mean disease duration was 84 (±80) months for the entire cohort with no difference seen between the two groups. No difference was seen in clinical symptoms, disability, or outcome measures between the two groups after correcting for multiple comparisons. Conclusions Minor EMG abnormalities were not associated with phenotypic differences in a clinical upper motor neuron disease population. These findings suggest that subtle EMG abnormalities can not necessarily be used as a prognostic tool in patients with clinical upper motor neuron disease. This study also demonstrates the availability of a large number of patients with upper motor neuron diseases within the NEALS network and suggests feasibility for conducting clinical trials in this population. PMID:26905909

  16. Primary Lateral Sclerosis and Early Upper Motor Neuron Disease: Characteristics of a Cross-Sectional Population.

    PubMed

    Fournier, Christina N; Murphy, Alyssa; Loci, Lorena; Mitsumoto, Hiroshi; Lomen-Hoerth, Catherine; Kisanuki, Yasushi; Simmons, Zachary; Maragakis, Nicholas J; McVey, April L; Al-Lahham, Tawfiq; Heiman-Patterson, Terry D; Andrews, Jinsy; McDonnell, Erin; Cudkowicz, Merit; Atassi, Nazem

    2016-03-01

    The goals of this study were to characterize clinical and electrophysiologic findings of subjects with upper motor neuron disease and to explore feasibility of clinical trials in this population. Twenty northeast amyotrophic lateral sclerosis consortium (northeast amyotrophic lateral sclerosis) sites performed chart reviews to identify active clinical pure upper motor neuron disease patients. Patients with hereditary spastic paraplegia or meeting revised El Escorial electrodiagnostic criteria for amyotrophic lateral sclerosis were excluded. Patients were classified into 2 groups according to the presence or absence of minor electromyography (EMG) abnormalities. Two hundred thirty-three subjects with upper motor neuron disease were identified; 217 had available EMG data. Normal EMGs were seen in 140 subjects, and 77 had minor denervation. Mean disease duration was 84 (±80) months for the entire cohort with no difference seen between the 2 groups. No difference was seen in clinical symptoms, disability, or outcome measures between the 2 groups after correcting for multiple comparisons. Minor EMG abnormalities were not associated with phenotypic differences in a clinical upper motor neuron disease population. These findings suggest that subtle EMG abnormalities can not necessarily be used as a prognostic tool in patients with clinical upper motor neuron disease. This study also demonstrates the availability of a large number of patients with upper motor neuron diseases within the northeast amyotrophic lateral sclerosis network and suggests feasibility for conducting clinical trials in this population.

  17. Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells.

    PubMed

    Siembab, Valerie C; Gomez-Perez, Laura; Rotterman, Travis M; Shneider, Neil A; Alvarez, Francisco J

    2016-06-15

    Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons, raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, such as Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (ER81(-/-) knockout), weakened (Egr3(-/-) knockout), or strengthened (mlcNT3(+/-) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their deselection and reduces motor axon synaptic density, and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells.

  18. Role of primary afferents in the developmental regulation of motor axon synapse numbers on Renshaw cells

    PubMed Central

    Siembab, Valerie C.; Gomez-Perez, Laura; Rotterman, Travis M.; Shneider, Neil A.; Alvarez, Francisco J.

    2015-01-01

    Motor function in mammalian species depends on the maturation of spinal circuits formed by a large variety of interneurons that regulate motoneuron firing and motor output. Interneuron activity is in turn modulated by the organization of their synaptic inputs, but the principles governing the development of specific synaptic architectures unique to each premotor interneuron are unknown. For example, Renshaw cells receive, at least in the neonate, convergent inputs from sensory afferents (likely Ia) and motor axons raising the question of whether they interact during Renshaw cell development. In other well-studied neurons, like Purkinje cells, heterosynaptic competition between inputs from different sources shapes synaptic organization. To examine the possibility that sensory afferents modulate synaptic maturation on developing Renshaw cells, we used three animal models in which afferent inputs in the ventral horn are dramatically reduced (Er81(−/−) knockout), weakened (Egr3(−/−) knockout) or strengthened (mlcNT3(+/−) transgenic). We demonstrate that increasing the strength of sensory inputs on Renshaw cells prevents their de-selection and reduces motor axon synaptic density and, in contrast, absent or diminished sensory afferent inputs correlate with increased densities of motor axons synapses. No effects were observed on other glutamatergic inputs. We conclude that the early strength of Ia synapses influences their maintenance or weakening during later development and that heterosynaptic influences from sensory synapses during early development regulates the density and organization of motor inputs on mature Renshaw cells. PMID:26660356

  19. A qualitative study of the cultural changes in primary care organisations needed to implement clinical governance.

    PubMed

    Marshall, Martin; Sheaff, Rod; Rogers, Anne; Campbell, Stephen; Halliwell, Shirley; Pickard, Susan; Sibbald, Bonnie; Roland, Martin

    2002-08-01

    It is commony claimed that changing the culture of health organisations is a fundamental prerequisite for improving the National Health Service (NHS). Little is currently known about the nature or importance of culture and cultural change in primary care groups and trusts (PCG/Ts) or their constituent general practices. To investigate the importance of culture and cultural change for the implementation of clinical governance in general practice by PCG/Ts, to identify perceived desirable and undesirable cultural attributes of general practice, and to describe potential facilitators and barriers to changing culture. Qualitative: case studies using data derived from semi-structured interviews and review of documentary evidence. Fifty senior non-clinical and clinical managers from 12 purposely sampled PCGs or trusts in England. Senior primary care managers regard culture and cultural change as fundamental aspects of clinical governance. The most important desirable cultural traits were the value placed on a commitment to public accountability by the practices, their willingness to work together and learn from each other, and the ability to be self-critical and learn from mistakes. The main barriers to cultural change were the high level of autonomy of practices and the perceived pressure to deliver rapid measurable changes in general practice. The culture of general practice is perceived to be an important component of health system reform and quality improvement. This study develops our understanding of a changing organisational culture in primary care; however, further work is required to determine whether culture is a useful practical lever for initiating or managing improvement.

  20. A qualitative study of the cultural changes in primary care organisations needed to implement clinical governance.

    PubMed Central

    Marshall, Martin; Sheaff, Rod; Rogers, Anne; Campbell, Stephen; Halliwell, Shirley; Pickard, Susan; Sibbald, Bonnie; Roland, Martin

    2002-01-01

    BACKGROUND: It is commony claimed that changing the culture of health organisations is a fundamental prerequisite for improving the National Health Service (NHS). Little is currently known about the nature or importance of culture and cultural change in primary care groups and trusts (PCG/Ts) or their constituent general practices. AIMS: To investigate the importance of culture and cultural change for the implementation of clinical governance in general practice by PCG/Ts, to identify perceived desirable and undesirable cultural attributes of general practice, and to describe potential facilitators and barriers to changing culture. DESIGN: Qualitative: case studies using data derived from semi-structured interviews and review of documentary evidence. SETTING: Fifty senior non-clinical and clinical managers from 12 purposely sampled PCGs or trusts in England. RESULTS: Senior primary care managers regard culture and cultural change as fundamental aspects of clinical governance. The most important desirable cultural traits were the value placed on a commitment to public accountability by the practices, their willingness to work together and learn from each other, and the ability to be self-critical and learn from mistakes. The main barriers to cultural change were the high level of autonomy of practices and the perceived pressure to deliver rapid measurable changes in general practice. CONCLUSIONS: The culture of general practice is perceived to be an important component of health system reform and quality improvement. This study develops our understanding of a changing organisational culture in primary care; however, further work is required to determine whether culture is a useful practical lever for initiating or managing improvement. PMID:12171222

  1. The Effect of Organizational Trust on the Culture of Teacher Leadership in Primary Schools

    ERIC Educational Resources Information Center

    Demir, Kamile

    2015-01-01

    The purpose of this research is to examine the effect of the level of trust of primary school teachers towards their organization in relation to their perceptions of the school having a culture of teacher leadership. Participants of the study consisted of 378 teachers working in Burdur public primary schools. The data collection tool used two…

  2. Turkish Primary School Teachers' Perceptions of School Culture Regarding ICT Integration

    ERIC Educational Resources Information Center

    Tezci, Erdogan

    2011-01-01

    The current study aimed at identifying Turkish primary school teachers' perceptions of school culture regarding ICT integration in education. In addition, the current study was designed to investigate factors that might influence their perceptions. The participants were 1540 primary school teachers. The findings revealed that the teachers'…

  3. Turkish Primary School Teachers' Perceptions of School Culture Regarding ICT Integration

    ERIC Educational Resources Information Center

    Tezci, Erdogan

    2011-01-01

    The current study aimed at identifying Turkish primary school teachers' perceptions of school culture regarding ICT integration in education. In addition, the current study was designed to investigate factors that might influence their perceptions. The participants were 1540 primary school teachers. The findings revealed that the teachers'…

  4. Meaningful Cultural Learning by Imitative Participation: The Case of Abstract Thinking in Primary School

    ERIC Educational Resources Information Center

    van Oers, Bert

    2012-01-01

    The article describes a theory-driven approach to meaningful learning in primary schools, based on the Vygotskian cultural-historical theory of human development and learning. This approach is elaborated into an educational concept called "developmental education" that is implemented in the Netherlands in many primary schools. In this…

  5. Human primary mixed brain cultures: preparation, differentiation, characterization and application to neuroscience research.

    PubMed

    Ray, Balmiki; Chopra, Nipun; Long, Justin M; Lahiri, Debomoy K

    2014-09-16

    Culturing primary cortical neurons is an essential neuroscience technique. However, most cultures are derived from rodent brains and standard protocols for human brain cultures are sparse. Herein, we describe preparation, maintenance and major characteristics of a primary human mixed brain culture, including neurons, obtained from legally aborted fetal brain tissue. This approach employs standard materials and techniques used in the preparation of rodent neuron cultures, with critical modifications. This culture has distinct differences from rodent cultures. Specifically, a significant numbers of cells in the human culture are derived from progenitor cells, and the yield and survival of the cells grossly depend on the presence of bFGF. In the presence of bFGF, this culture can be maintained for an extended period. Abundant productions of amyloid-β, tau and proteins make this a powerful model for Alzheimer's research. The culture also produces glia and different sub-types of neurons. We provide a well-characterized methodology for human mixed brain cultures useful to test therapeutic agents under various conditions, and to carry forward mechanistic and translational studies for several brain disorders.

  6. Proteomic Characterization of Primary Mouse Hepatocytes in Collagen Monolayer and Sandwich Culture.

    PubMed

    Orsini, Malina; Sperber, Saskia; Noor, Fozia; Hoffmann, Esther; Weber, Susanne N; Hall, Rabea A; Lammert, Frank; Heinzle, Elmar

    2017-06-08

    Dedifferentiation of primary hepatocytes in vitro makes their application in long-term studies difficult. Embedding hepatocytes in a sandwich of extracellular matrix is reported to delay the dedifferentiation process to some extent. In this study, we compared the intracellular proteome of primary mouse hepatocytes (PMH) in conventional monolayer cultures (ML) to collagen sandwich culture (SW) after 1 day and 5 days of cultivation. Quantitative proteome analysis of PMH showed no differences between collagen SW and ML cultures after 1 day. Glycolysis and gluconeogenesis were strongly affected by long-term cultivation in both ML and SW cultures. Interestingly, culture conditions had no effect on cellular lipid metabolism. After 5 days, PMH in collagen SW and ML cultures exhibit characteristic indications of oxidative stress. However, in the SW culture the defense system against oxidative stress is significantly up-regulated to deal with this, whereas in the ML culture a down-regulation of these important enzymes takes place. Regarding the multiple effects of ROS and oxidative stress in cells, we conclude that the down-regulation of these enzymes seem to play a role in the loss of hepatic function observed in the ML cultivation. In addition, enzymes of the urea cycle were clearly down-regulated in ML culture. Proteomics confirms lack in oxidative stress defense mechanisms as the major characteristic of hepatocytes in monolayer cultures compared to sandwich cultures. J. Cell. Biochem. 9999: 1-8, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Competition with Primary Sensory Afferents Drives Remodeling of Corticospinal Axons in Mature Spinal Motor Circuits.

    PubMed

    Jiang, Yu-Qiu; Zaaimi, Boubker; Martin, John H

    2016-01-06

    Injury to the mature motor system drives significant spontaneous axonal sprouting instead of axon regeneration. Knowing the circuit-level determinants of axonal sprouting is important for repairing motor circuits after injury to achieve functional rehabilitation. Competitive interactions are known to shape corticospinal tract axon outgrowth and withdrawal during development. Whether and how competition contributes to reorganization of mature spinal motor circuits is unclear. To study this question, we examined plastic changes in corticospinal axons in response to two complementary proprioceptive afferent manipulations: (1) enhancing proprioceptive afferents activity by electrical stimulation; or (2) diminishing their input by dorsal rootlet rhizotomy. Experiments were conducted in adult rats. Electrical stimulation produced proprioceptive afferent sprouting that was accompanied by significant corticospinal axon withdrawal and a decrease in corticospinal connections on cholinergic interneurons in the medial intermediate zone and C boutons on motoneurons. In contrast, dorsal rootlet rhizotomy led to a significant increase in corticospinal connections, including those on cholinergic interneurons; C bouton density increased correspondingly. Motor cortex-evoked muscle potentials showed parallel changes to those of corticospinal axons, suggesting that reciprocal corticospinal axon changes are functional. Using the two complementary models, we showed that competitive interactions between proprioceptive and corticospinal axons are an important determinant in the organization of mature corticospinal axons and spinal motor circuits. The activity- and synaptic space-dependent properties of the competition enables prediction of the remodeling of spared corticospinal connection and spinal motor circuits after injury and informs the target-specific control of corticospinal connections to promote functional recovery. Neuroplasticity is limited in maturity, but it is promoted

  8. Competition with Primary Sensory Afferents Drives Remodeling of Corticospinal Axons in Mature Spinal Motor Circuits

    PubMed Central

    Jiang, Yu-Qiu; Zaaimi, Boubker

    2016-01-01

    Injury to the mature motor system drives significant spontaneous axonal sprouting instead of axon regeneration. Knowing the circuit-level determinants of axonal sprouting is important for repairing motor circuits after injury to achieve functional rehabilitation. Competitive interactions are known to shape corticospinal tract axon outgrowth and withdrawal during development. Whether and how competition contributes to reorganization of mature spinal motor circuits is unclear. To study this question, we examined plastic changes in corticospinal axons in response to two complementary proprioceptive afferent manipulations: (1) enhancing proprioceptive afferents activity by electrical stimulation; or (2) diminishing their input by dorsal rootlet rhizotomy. Experiments were conducted in adult rats. Electrical stimulation produced proprioceptive afferent sprouting that was accompanied by significant corticospinal axon withdrawal and a decrease in corticospinal connections on cholinergic interneurons in the medial intermediate zone and C boutons on motoneurons. In contrast, dorsal rootlet rhizotomy led to a significant increase in corticospinal connections, including those on cholinergic interneurons; C bouton density increased correspondingly. Motor cortex-evoked muscle potentials showed parallel changes to those of corticospinal axons, suggesting that reciprocal corticospinal axon changes are functional. Using the two complementary models, we showed that competitive interactions between proprioceptive and corticospinal axons are an important determinant in the organization of mature corticospinal axons and spinal motor circuits. The activity- and synaptic space-dependent properties of the competition enables prediction of the remodeling of spared corticospinal connection and spinal motor circuits after injury and informs the target-specific control of corticospinal connections to promote functional recovery. SIGNIFICANCE STATEMENT Neuroplasticity is limited in maturity

  9. The activity of the primary motor cortex ipsilateral to the exercising hand decreases during repetitive handgrip exercise.

    PubMed

    Shibuya, Kenichi

    2011-12-01

    The brain function controlling muscle force production is not yet fully understood. The purpose of this study was to examine bilateral primary motor cortex (M1) oxygenation during static-handgrip exercises performed with the right hand (60% maximal voluntary contraction; 10 s exercise/75 s rest; five sets). Twelve healthy, right-handed male subjects participated in this study. Near-infrared spectroscopy probes were positioned over the bilateral M1 to measure cortical oxygenation during handgrip exercises. The maximum values of the changes in concentrations of oxyhemoglobin (HbO(2)) and deoxyhemoglobin (Hb) across the trials (i) did not change significantly during the contralateral M1 activation (p > 0.05), whereas (ii) in the case of the ipsilateral M1 activation a significant (p < 0.05) decrease in HbO(2) and a significant (p < 0.01) decrease in Hb could be measured. The activation in ipsilateral M1 at the fifth trial was significantly decreased compared with that in the first trial (HbO(2): p < 0.001; Hb: p < 0.001). The present results suggest that the ipsilateral M1 is recruited during the motor task in compensation for the contralateral M1 and the habituation to motor task might alter the efficiency for interaction of the ipsilateral M1 to the contralateral M1. The interhemispheric interaction might change due to habituation to motor task.

  10. Primary outgrowth cultures are a reliable source of human pancreatic stellate cells.

    PubMed

    Han, Song; Delitto, Daniel; Zhang, Dongyu; Sorenson, Heather L; Sarosi, George A; Thomas, Ryan M; Behrns, Kevin E; Wallet, Shannon M; Trevino, Jose G; Hughes, Steven J

    2015-11-01

    Recent advances demonstrate a critical yet poorly understood role for the pancreatic stellate cell (PSC) in the pathogenesis of chronic pancreatitis (CP) and pancreatic cancer (PC). Progress in this area has been hampered by the availability, fidelity, and/or reliability of in vitro models of PSCs. We examined whether outgrowth cultures from human surgical specimens exhibited reproducible phenotypic and functional characteristics of PSCs. PSCs were cultured from surgical specimens of healthy pancreas, CP and PC. Growth dynamics, phenotypic characteristics, soluble mediator secretion profiles and co-culture with PC cells both in vitro and in vivo were assessed. Forty-seven primary cultures were established from 52 attempts, demonstrating universal α-smooth muscle actin and glial fibrillary acidic protein but negligible epithelial surface antigen expression. Modification of culture conditions consistently led to cytoplasmic lipid accumulation, suggesting induction of a quiescent phenotype. Secretion of growth factors, chemokines and cytokines did not significantly differ between donor pathologies, but did evolve over time in culture. Co-culture of PSCs with established PC cell lines resulted in significant changes in levels of multiple secreted mediators. Primary PSCs co-inoculated with PC cells in a xenograft model led to augmented tumor growth and metastasis. Therefore, regardless of donor pathology, outgrowth cultures produce PSCs that demonstrate consistent growth and protein secretion properties. Primary cultures from pancreatic surgical specimens, including malignancies, may represent a reliable source of human PSCs.

  11. Gelatin for purification and proliferation of primary keratinocyte culture for use in chronic wounds and burns.

    PubMed

    Rahsaz, Marjan; Geramizadeh, Bita; Kaviani, Maryam; Marzban, Saeed

    2015-04-01

    Human epidermal keratinocytes are currently established as a treatment for burns and wounds and have laboratory applications. Keratinocyte culture contamination by unwanted cells and inhibition of cell proliferation are barriers in primary keratinocyte culture. According to the recent literature, these cells are hard to culture. The present study was conducted to evaluate the efficacy of gelatin-coated surfaces in keratinocyte cultures. After enzymatic isolation of keratinocytes from normal epidermis by trypsin, the cells were cultured on gelatin-coated flasks in serum-free medium. Another group of cells were cultured as a control group without gelatin coating. We showed positive effects of surface coating with gelatin on the primary culture of keratinocytes. Culture of these cells on a gelatincoated surface showed better proliferation with suitable morphology. By using gelatin, adhesion of these cells to the surface was more efficient and without contamination by small round cells. Successful primary culture of keratinocytes on a gelatin-coated surface may provide better yield and optimal number of cells for research and clinical applications.

  12. Ganoderma Lucidum polysaccharides protect against MPP+ and rotenone-induced apoptosis in primary dopaminergic cell cultures through inhibiting oxidative stress

    PubMed Central

    Guo, Shan-Shan; Cui, Xiao-Lan; Rausch, Wolf-Dieter

    2016-01-01

    Oxidative stress plays a pivotal role in the progressive neurodegeneration in Parkinson’s disease (PD) which is responsible for disabling motor abnormalities in more than 6.5 million people worldwide. Polysaccharides are the main active constituents from Ganoderma lucidum which is characterized with anti-oxidant, antitumor and immunostimulant properties. In the present study, primary dopaminergic cell cultures prepared from embryonic mouse mesencephala were used to investigate the neuroprotective effects and the potential mechanisms of Ganoderma lucidum polysaccharides (GLP) on the degeneration of dopaminergic neurons induced by the neurotoxins methyl-4-phenylpyridine (MPP+) and rotenone. Results revealed that GLP can protect dopamine neurons against MPP+ and rotenone at the concentrations of 100, 50 and 25 μg/ml in primary mesencephalic cultures in a dose-dependent manner. Interestingly, either with or without neurotoxin treatment, GLP treatment elevated the survival of THir neurons, and increased the length of neurites of dopaminergic neurons. The Trolox equivalent anti-oxidant capacity (TEAC) of GLP was determined to be 199.53 μmol Trolox/g extract, and the decrease of mitochondrial complex I activity induced by MPP+ and rotenone was elevated by GLP treatment (100, 50, 25 and 12.5 μg/ml) in a dose dependent manner. Furthermore, GLP dramatically decreased the relative number of apoptotic cells and increased the declining mitochondrial membrane potential (ΔΨm) induced by MPP+ and rotenone in a dose-dependent manner. In addition, GLP treatment reduced the ROS formation induced by MPP+ and rotenone at the concentrations of 100, 50 and 25 μg/ml in a dose-dependent manner. Our study indicates that GLP possesses neuroprotective properties against MPP+ and rotenone neurotoxicity through suppressing oxidative stress in primary mesencephalic dopaminergic cell culture owning to its antioxidant activities. PMID:27335703

  13. Characterization of benzodiazepine receptors in primary cultures of fetal mouse brain and spinal cord neurons.

    PubMed

    Huang, A; Barker, J L; Paul, S M; Moncada, V; Skolnick, P

    1980-05-26

    Primary cultures of fetal mouse brain and spinal cord were examined for the presence of binding sites for [3H]diazepam. Both brain and spinal cord cultures contain high affinity binding sites which resemble benzodiazepine receptors found in mammalian CNS with respect to both pharmacologic profile and response to exogenously applied GABA. These observations, coupled with the electrophysiologic properties of these cells suggest that primary cultures of fetal mouse brain and spinal cord may be valid models for studying the role and regulation of the benzodiazepine receptor.

  14. Differential effects of primary motor cortex and cerebellar transcranial direct current stimulation on motor learning in healthy individuals: A randomized double-blind sham-controlled study.

    PubMed

    Ehsani, F; Bakhtiary, A H; Jaberzadeh, S; Talimkhani, A; Hajihasani, A

    2016-11-01

    The purpose of study was to compare the effect of primary motor cortex (M1) and cerebellar anodal transcranial direct current stimulation (a-tDCS) on online and offline motor learning in healthy individuals. Fifty-nine healthy volunteers were randomly divided into three groups (n=20 in two experimental groups and n=19 in sham-control group). One experimental group received M1a-tDCSand another received cerebellar a-tDCS. The main outcome measure were response time (RT) and number of errors during serial response time test (SRTT) which were assessed prior, 35min and 48h after the interventions. Reduction of response time (RT) and error numbers at last block of the test compared to the first block was considered online learning. Comparison of assessments during retention tests was considered as short-term and long-term offline learning. Online RT reduction was not different among groups (P>0.05), while online error reduction was significantly greater in cerebellar a-tDCS than sham-control group (P<0.017). Moreover, a-tDCS on both M1 and cerebellar regions produced more long-term offline learning as compared to sham tDCS (P<0.01), while short-term offline RT reduction was significantly greater in M1a-tDCS than sham-control group (P<0.05). The findings indicated that although cerebellar a-tDCS enhances online learning and M1a-tDCS has more effect on short-term offline learning, both M1 and cerebellar a-tDCS can be used as a boosting technique for improvement of offline motor learning in healthy individuals.

  15. Cryopreservation and lentiviral-mediated genetic modification of human primary cultured corneal endothelial cells.

    PubMed

    Suh, Leejee H; Zhang, Cheng; Chuck, Roy S; Stark, Walter J; Naylor, Stuart; Binley, Katie; Chakravarti, Shukti; Jun, Albert S

    2007-07-01

    To determine the viability and potential usefulness of cryopreserved human primary cultured corneal endothelial cells by characterizing their morphology, gene expression, and ability for genetic modification by the lentiviral vector equine infectious anemia virus (EIAV). Primary cultured endothelial cells were dissociated from human corneas and grown in organ culture medium. Corneal endothelial cell origin was confirmed by morphology and immunostaining with polyclonal anti-collagen VIII antibodies. Cells of different passages were cryopreserved in medium containing dimethyl sulfoxide and were assessed after thawing for morphology, proliferative capacity, gene expression, and ability to form cell-cell junctions. EIAV encoding enhanced green fluorescent protein (eGFP) was used to transduce cryopreserved human corneal endothelial cells. Transduced cells were then sorted by fluorescence-activated cell sorting (FACS) and imaged with fluorescence microscopy. Cryopreserved, primary, cultured human corneal endothelial cells are viable and retain their ability to proliferate, produce collagen VIII, and express ZO-1, a tight-junction protein. EIAV-based gene transfer of eGFP is highly efficient and nontoxic to cryopreserved human primary cultured corneal endothelial cells. These genetically modified cells can be selected to nearly pure populations with FACS sorting. Human primary cultured corneal endothelial cells retain their phenotypic properties after cryopreservation. The ability to store, genetically modify, and sort these cells through FACS to pure populations has the potential to greatly expand their future therapeutic application to treat corneal endothelial disorders.

  16. Task-dependent modulation of excitatory and inhibitory functions within the human primary motor cortex.

    PubMed

    Tinazzi, Michele; Farina, Simona; Tamburin, Stefano; Facchini, Stefano; Fiaschi, Antonio; Restivo, Domenico; Berardelli, Alfredo

    2003-05-01

    We evaluated motor evoked potentials (MEPs) and duration of the cortical silent period (CSP) from the right first dorsal interosseous (FDI) muscle to transcranial magnetic stimulation (TMS) of the left motor cortex in ten healthy subjects performing different manual tasks. They abducted the index finger alone, pressed a strain gauge with the thumb and index finger in a pincer grip, and squeezed a 4-cm brass cylinder with all digits in a power grip. The level of FDI EMG activity across tasks was kept constant by providing subjects with acoustic-visual feedback of their muscle activity. The TMS elicited larger amplitude FDI MEPs during pincer and power grip than during the index finger abduction task, and larger amplitude MEPs during pincer gripping than during power gripping. The CSP was shorter during pincer and power grip than during the index finger abduction task and shorter during power gripping than during pincer gripping. These results suggest excitatory and inhibitory task-dependent changes in the motor cortex. Complex manual tasks (pincer and power gripping) elicit greater motor cortical excitation than a simple task (index finger abduction) presumably because they activate multiple synergistic muscles thus facilitating corticomotoneurons. The finger abduction task probably yielded greater motor cortical inhibition than the pincer and power tasks because muscles uninvolved in the task activated the cortical inhibitory circuit. Increased cortical excitatory and inhibitory functions during precision tasks (pincer gripping) probably explain why MEPs have larger amplitudes and CSPs have longer durations during pincer gripping than during power gripping.

  17. Establishment of a primary culture of polymorphous low grade adenocarcinoma cells.

    PubMed

    Teixeira, Lucas Novaes; Montalli, Victor Angelo Martins; de Oliveira, Silvia Borges Pimentel; Toledo, Thais Fernanda Santos; Martinez, Elizabeth Ferreira; de Araújo, Vera Cavalcanti

    2017-10-01

    The aim of the present study was to establish a primary cell culture derived from polymorphous low grade adenocarcinoma (PLGA). The neoplastic cells were derived from a 57-year-old female patient diagnosed with PLGA. A fragment of the tumor was collected and submitted to enzymatic digestion followed by centrifugation on a Percoll gradient. The cell population was characterized by means of immunofluorescence and detection of PRKD1 gene mutations. Epifluorescence analysis of the primary culture revealed that the malignant epithelial cells were predominantly polygonal in shape and positive for cytokeratin 7, vimentin, and S100. The doubling time of the cell culture was 86.73h. The restriction digestion assay showed that the neoplastic cells possess PRKD1 gene mutations. The establishment of primary cell culture derived from PLGA should be considered a useful tool for molecular analysis of this salivary gland tumor. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Numerical calculation of primary slot leakage inductance of a Single-sided HTS linear induction motor used for linear metro

    NASA Astrophysics Data System (ADS)

    Li, Dong; Wen, Yinghong; Li, Weili; Fang, Jin; Cao, Junci; Zhang, Xiaochen; Lv, Gang

    2017-03-01

    In the paper, the numerical method calculating asymmetric primary slot leakage inductances of Single-sided High-Temperature Superconducting (HTS) Linear Induction Motor (HTS LIM) is presented. The mathematical and geometric models of three-dimensional nonlinear transient electromagnetic field are established and the boundary conditions are also given. The established model is solved by time-stepping Finite Element Method (FEM). Then, the three-phase asymmetric primary slot leakage inductances under different operation conditions are calculated by using the obtained electromagnetic field distribution. The influences of the special effects such as longitudinal end effects, transversal edge effects, etc. on the primary slot leakage inductance are investigated. The presented numerical method is validated by experiments carried out on a 3.5 kW prototype with copper wires which has the same structures with the HTS LIM.

  19. An improved protocol for primary culture of cardiomyocyte from neonatal mice.

    PubMed

    Sreejit, P; Kumar, Suresh; Verma, Rama S

    2008-01-01

    The primary culture of neonatal mice cardiomyocyte model enables researchers to study and understand the morphological, biochemical, and electrophysiological characteristics of the heart, besides being a valuable tool for pharmacological and toxicological studies. Because cardiomyocytes do not proliferate after birth, primary myocardial culture is recalcitrant. The present study describes an improved method for rapid isolation of cardiomyocytes from neonatal mice, as well as the maintenance and propagation of such cultures for the long term. Immunocytochemical and gene expression data also confirmed the presence of several cardiac markers in the beating cells during the long-term culture condition used in this protocol. The whole culture process can be effectively shortened by reducing the enzyme digestion period and the cardiomyocyte enrichment step.

  20. Investigating the establishment of primary cell culture from different abalone (Haliotis midae) tissues

    PubMed Central

    Auzoux-Bordenave, Stéphanie; Niesler, Carola; Roodt-Wilding, Rouvay

    2010-01-01

    The abalone, Haliotis midae, is the most valuable commodity in South African aquaculture. The increasing demand for marine shellfish has stimulated research on the biology and physiology of target species in order to improve knowledge on growth, nutritional requirements and pathogen identification. The slow growth rate and long generation time of abalone restrict efficient design of in vivo experiments. Therefore, in vitro systems present an attractive alternative for short term experimentation. The use of marine invertebrate cell cultures as a standardised and controlled system to study growth, endocrinology and disease contributes to the understanding of the biology of economically important molluscs. This paper investigates the suitability of two different H. midae tissues, larval and haemocyte, for establishing primary cell cultures. Cell cultures are assessed in terms of culture initiation, cell yield, longevity and susceptibility to contamination. Haliotis midae haemocytes are shown to be a more feasible tissue for primary cell culture as it could be maintained without contamination more readily than larval cell cultures. The usefulness of short term primary haemocyte cultures is demonstrated here with a growth factor trial. Haemocyte cultures can furthermore be used to relate phenotypic changes at the cellular level to changes in gene expression at the molecular level. PMID:20680682

  1. Investigating the establishment of primary cell culture from different abalone (Haliotis midae) tissues.

    PubMed

    van der Merwe, Mathilde; Auzoux-Bordenave, Stéphanie; Niesler, Carola; Roodt-Wilding, Rouvay

    2010-07-01

    The abalone, Haliotis midae, is the most valuable commodity in South African aquaculture. The increasing demand for marine shellfish has stimulated research on the biology and physiology of target species in order to improve knowledge on growth, nutritional requirements and pathogen identification. The slow growth rate and long generation time of abalone restrict efficient design of in vivo experiments. Therefore, in vitro systems present an attractive alternative for short term experimentation. The use of marine invertebrate cell cultures as a standardised and controlled system to study growth, endocrinology and disease contributes to the understanding of the biology of economically important molluscs. This paper investigates the suitability of two different H. midae tissues, larval and haemocyte, for establishing primary cell cultures. Cell cultures are assessed in terms of culture initiation, cell yield, longevity and susceptibility to contamination. Haliotis midae haemocytes are shown to be a more feasible tissue for primary cell culture as it could be maintained without contamination more readily than larval cell cultures. The usefulness of short term primary haemocyte cultures is demonstrated here with a growth factor trial. Haemocyte cultures can furthermore be used to relate phenotypic changes at the cellular level to changes in gene expression at the molecular level.

  2. Dual-hemisphere transcranial direct current stimulation over primary motor cortex enhances consolidation of a ballistic thumb movement.

    PubMed

    Koyama, Soichiro; Tanaka, Satoshi; Tanabe, Shigeo; Sadato, Norihiro

    2015-02-19

    Transcranial direct current stimulation (tDCS) is a noninvasive technique that modulates motor performance and learning. Previous studies have shown that tDCS over the primary motor cortex (M1) can facilitate consolidation of various motor skills. However, the effect of tDCS on consolidation of newly learned ballistic movements remains unknown. The present study tested the hypothesis that tDCS over M1 enhances consolidation of ballistic thumb movements in healthy adults. Twenty-eight healthy subjects participated in an experiment with a single-blind, sham-controlled, between-group design. Fourteen subjects practiced a ballistic movement with their left thumb during dual-hemisphere tDCS. Subjects received 1mA anodal tDCS over the contralateral M1 and 1mA cathodal tDCS over the ipsilateral M1 for 25min during the training session. The remaining 14 subjects underwent identical training sessions, except that dual-hemisphere tDCS was applied for only the first 15s (sham group). All subjects performed the task again at 1h and 24h later. Primary measurements examined improvement in peak acceleration of the ballistic thumb movement at 1h and 24h after stimulation. Improved peak acceleration was significantly greater in the tDCS group (144.2±15.1%) than in the sham group (98.7±9.1%) (P<0.05) at 24h, but not 1h, after stimulation. Thus, dual-hemisphere tDCS over M1 enhanced consolidation of ballistic thumb movement in healthy adults. Dual-hemisphere tDCS over M1 may be useful to improve elemental motor behaviors, such as ballistic movements, in patients with subcortical strokes. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  3. Primary control of a Mach scale swashplateless rotor using brushless DC motor actuated trailing edge flaps

    NASA Astrophysics Data System (ADS)

    Saxena, Anand

    The focus of this research was to demonstrate a four blade rotor trim in forward flight using integrated trailing edge flaps instead of using a swashplate controls. A compact brushless DC motor was evaluated as an on-blade actuator, with the possibility of achieving large trailing edge flap amplitudes. A control strategy to actuate the trailing edge flap at desired frequency and amplitude was developed and large trailing edge flap amplitudes from the motor (instead of rotational motion) were obtained. Once the actuator was tested on the bench-top, a lightweight mechanism was designed to incorporate the motor in the blade and actuate the trailing edge flaps. A six feet diameter, four bladed composite rotor with motor-flap system integrated into the NACA 0012 airfoil section was fabricated. Systematic testing was carried out for a range of load conditions, first in the vacuum chamber followed by hover tests. Large trailing edge flap deflections were observed during the hover testing, and a peak to peak trailing edge flap amplitude of 18 degree was achieved at 2000 rotor RPM with hover tip Mach number of 0.628. A closed loop controller was designed to demonstrate trailing edge flap mean position and the peak to peak amplitude control. Further, a soft pitch link was designed and fabricated, to replace the stiff pitch link and thereby reduce the torsional stiffness of the blade to 2/rev. This soft pitch link allowed for blade root pitch motion in response to the trailing edge flap inputs. Blade pitch response due to both steady as well as sinusoidal flap deflections were demonstrated. Finally, tests were performed in Glenn L. Martin wind tunnel using a model rotor rig to assess the performance of motor-flap system in forward flight. A swashplateless trim using brushless DC motor actuated trailing edge flaps was achieved for a rotor operating at 1200 RPM and an advance ratio of 0.28. Also, preliminary exploration was carried out to test the scalability of the motor

  4. Primary targets in photochemical inactivation of cells in culture

    NASA Astrophysics Data System (ADS)

    Berg, Kristian; Jones, Stuart G.; Prydz, Kristian; Moan, Johan

    1995-01-01

    The mechanisms of photoinactivation of NHIK 3025 cells in culture sensitized by tetrasulfonated phenylporphines (TPPS4) are described). Ultracentrifugation studies on postnuclear supernatants indicated that the intracellular distribution of TPPS4 resembles that of (beta) -N-acetyl-D-glucosaminidase ((beta) -AGA), a lysosomal marker enzyme, and that the cytosolic content of TPPS4 is below the detection limit of the ultracentrifugation method. Upon light exposure more than 90% of TPPS4 was lost from the lysosomal fractions, due to lysosomal rupture. The content of TPPS4 in the postnuclear supernatants was reduced by 30 - 40% upon exposure to light. This is most likely due to binding of TPPS4 to the nuclei, which were removed from the cell extracts before ultracentrifugation, after photochemical treatment. The unpolymerized form of tubulin seems to be an important target for the photochemical inactivation of NHIK 3025 cells. Since TPPS4 is mainly localized in lysosomes it was assumed that a dose of light disrupting a substantial number of lysosomes followed by microtubule depolymerization by nocodazole would enhance the sensitivity of the cells to photoinactivation. This was confirmed by using a colony-forming assay. The increased phototoxic effect exerted by such a treatment regime could be explained by an enhanced sensitivity of tubulin to light. Another cytosolic constituent, lactate dehydrogenase, was not photoinactivated by TPPS4 and light.

  5. Prevalence of Persistent Primary Reflexes and Motor Problems in Children with Reading Difficulties

    ERIC Educational Resources Information Center

    McPhillips, M.; Sheehy, N.

    2004-01-01

    It has been shown that some children with reading difficulties have underlying developmental delay and that this may be related to the persistence of primary reflexes. This study investigated the prevalence of persistent primary reflexes in the ordinary primary school population and how this related to other cognitive and social factors. Three…

  6. Prevalence of Persistent Primary Reflexes and Motor Problems in Children with Reading Difficulties

    ERIC Educational Resources Information Center

    McPhillips, M.; Sheehy, N.

    2004-01-01

    It has been shown that some children with reading difficulties have underlying developmental delay and that this may be related to the persistence of primary reflexes. This study investigated the prevalence of persistent primary reflexes in the ordinary primary school population and how this related to other cognitive and social factors. Three…

  7. Primary motor and sensory cortical areas communicate via spatiotemporally coordinated networks at multiple frequencies

    PubMed Central

    Arce-McShane, Fritzie I.; Ross, Callum F.; Takahashi, Kazutaka; Sessle, Barry J.; Hatsopoulos, Nicholas G.

    2016-01-01

    Skilled movements rely on sensory information to shape optimal motor responses, for which the sensory and motor cortical areas are critical. How these areas interact to mediate sensorimotor integration is largely unknown. Here, we measure intercortical coherence between the orofacial motor (MIo) and somatosensory (SIo) areas of cortex as monkeys learn to generate tongue-protrusive force. We report that coherence between MIo and SIo is reciprocal and that neuroplastic changes in coherence gradually emerge over a few days. These functional networks of coherent spiking and local field potentials exhibit frequency-specific spatiotemporal properties. During force generation, theta coherence (2–6 Hz) is prominent and exhibited by numerous paired signals; before or after force generation, coherence is evident in alpha (6–13 Hz), beta (15–30 Hz), and gamma (30–50 Hz) bands, but the functional networks are smaller and weaker. Unlike coherence in the higher frequency bands, the distribution of the phase at peak theta coherence is bimodal with peaks near 0° and ±180°, suggesting that communication between somatosensory and motor areas is coordinated temporally by the phase of theta coherence. Time-sensitive sensorimotor integration and plasticity may rely on coherence of local and large-scale functional networks for cortical processes to operate at multiple temporal and spatial scales. PMID:27091982

  8. Motor Performance of Primary Age Handicapped and Nonhandicapped Children in the Mainstream: A Comparison.

    ERIC Educational Resources Information Center

    Sherrill, Claudine; Kelly, Luke

    A comparative study was made of mentally retarded and nonhandicapped children in the first through third grades on motor performance as measured by running (50-yard dash), jumping (standing broad jump), and throwing (softball throw for distance). The subjects had received all of their physical education instruction in a mainstream setting since…

  9. Motor Performance of Primary Age Handicapped and Nonhandicapped Children in the Mainstream: A Comparison.

    ERIC Educational Resources Information Center

    Sherrill, Claudine; Kelly, Luke

    A comparative study was made of mentally retarded and nonhandicapped children in the first through third grades on motor performance as measured by running (50-yard dash), jumping (standing broad jump), and throwing (softball throw for distance). The subjects had received all of their physical education instruction in a mainstream setting since…

  10. Efficient establishment of primary fibroblast cultures from the hawksbill sea turtle (Eretmochelys imbricata).

    PubMed

    Fukuda, Tomokazu; Kurita, Jun; Saito, Tomomi; Yuasa, Kei; Kurita, Masanobu; Donai, Kenichiro; Nitto, Hiroshi; Soichi, Makoto; Nishimori, Katsuhiko; Uchida, Takafumi; Isogai, Emiko; Onuma, Manabu; Sone, Hideko; Oseko, Norihisa; Inoue-Murayama, Miho

    2012-12-01

    The hawksbill sea turtle (Eretmochelys imbricata) is a critically endangered species at a risk of extinction. Preservation of the genomic and cellular information of endangered animals is important for future genetic and biological studies. Here, we report the efficient establishment of primary fibroblast cultures from skin tissue of the hawksbill sea turtle. We succeeded in establishing 19 primary cultures from 20 hawksbill sea turtle individuals (a success rate of 95%). These cells exhibited a fibroblast-like morphology and grew optimally at a temperature of 26°C, but experienced a loss of viability when cultured at 37°C. Chromosomal analysis using the primary cells derived here revealed that hawksbill sea turtles have a 2n = 56 karyotype. Furthermore, we showed that our primary cell cultures are free of several fish-related viruses, and this finding is important for preservation purposes. To our knowledge, this report is the first to describe primary cell cultures established from normal tissues of the hawksbill sea turtle. The results will contribute to the preservation of biodiversity, especially for the sea turtles that are critically endangered owing to human activities.

  11. Measurement tools and process indicators of patient safety culture in primary care. A mixed methods study by the LINNEAUS collaboration on patient safety in primary care

    PubMed Central

    Parker, Dianne; Wensing, Michel; Esmail, Aneez; Valderas, Jose M

    2015-01-01

    ABSTRACT Background: There is little guidance available to healthcare practitioners about what tools they might use to assess the patient safety culture. Objective: To identify useful tools for assessing patient safety culture in primary care organizations in Europe; to identify those aspects of performance that should be assessed when investigating the relationship between safety culture and performance in primary care. Methods: Two consensus-based studies were carried out, in which subject matter experts and primary healthcare professionals from several EU states rated (a) the applicability to their healthcare system of several existing safety culture assessment tools and (b) the appropriateness and usefulness of a range of potential indicators of a positive patient safety culture to primary care settings. The safety culture tools were field-tested in four countries to ascertain any challenges and issues arising when used in primary care. Results: The two existing tools that received the most favourable ratings were the Manchester patient safety framework (MaPsAF primary care version) and the Agency for healthcare research and quality survey (medical office version). Several potential safety culture process indicators were identified. The one that emerged as offering the best combination of appropriateness and usefulness related to the collection of data on adverse patient events. Conclusion: Two tools, one quantitative and one qualitative, were identified as applicable and useful in assessing patient safety culture in primary care settings in Europe. Safety culture indicators in primary care should focus on the processes rather than the outcomes of care. PMID:26339832

  12. Assessment of patient safety culture in primary care setting, Al-Mukala, Yemen.

    PubMed

    Webair, Hana H; Al-Assani, Salwa S; Al-Haddad, Reema H; Al-Shaeeb, Wafa H; Bin Selm, Manal A; Alyamani, Abdulla S

    2015-10-13

    Patient safety culture in primary care is the first step to achieve high quality health care. This study aims to provide a baseline assessment of patient safety culture in primary care settings in Al-Mukala, Yemen as a first published study from a least developed country. A survey was conducted in primary healthcare centres and units in Al-Mukala District, Yemen. A comprehensive sample from the available 16 centres was included. An Arabic version of the Medical Office Survey on Patient Safety Culture was distributed to all health workers (110). Participants were physicians, nurses and administrative staff. The response rate from the participating centres was 71 %. (N = 78). The percent positive responses of the items is equal to the percentage of participants who answered positively. Composite scores were calculated by averaging the percent positive response on the items within a dimension. Positive safety culture was defined as 60 % or more positive responses on items or dimensions. Patient safety culture was perceived to be generally positive with the exception of the dimensions of 'Communication openness', 'Work pressure and pace' and 'Patient care tracking/follow-up', as the percent positive response of these dimensions were 58, 57, and 52 % respectively. Overall, positive rating on quality and patient safety were low (49 and 46 % respectively). Although patient safety culture in Al-Mukala primary care setting is generally positive, patient safety and quality rating were fairly low. Implementation of a safety and quality management system in Al-Mukala primary care setting are paramount. Further research is needed to confirm the applicability of the Medical Office Survey on Patient Safety Culture (MOSPSC) for Al-Mukala primary care.

  13. 10 CFR 830 Major Modification Determination for Replacement of ATR Primary Coolant Pumps and Motors

    SciTech Connect

    Noel Duckwitz

    2011-05-01

    The continued safe and reliable operation of the ATR is critical to the Department of Energy (DOE) Office of Nuclear Energy (NE) mission. While ATR is safely fulfilling current mission requirements, a variety of aging and obsolescence issues challenge ATR engineering and maintenance personnel’s capability to sustain ATR over the long term. First documented in a series of independent assessments, beginning with an OA Environmental Safety and Health Assessment conducted in 2003, the issues were validated in a detailed Material Condition Assessment (MCA) conducted as a part of the ATR Life Extension Program in 2007.Accordingly, near term replacement of aging and obsolescent original ATR equipment has become important to ensure ATR capability in support of NE’s long term national missions. To that end, a mission needs statement has been prepared for a non-major system acquisition which is comprised of three interdependent subprojects. The first project will replace the existent diesel-electrical bus (E-3), switchgear, and the 50-year-old obsolescent marine diesels with commercial power that is backed with safety related emergency diesel generators, switchgear, and uninterruptible power supply (UPS). The second project, the subject of this major modification determination, will replace the four, obsolete, original primary coolant pumps (PCPs) and motors. Completion of this and the two other age-related projects (replacement of the ATR diesel bus [E-3] and switchgear and replacement of the existent emergency firewater injection system) will resolve major age-related operational issues plus make a significant contribution in sustaining the ATR safety and reliability profile. The major modification criteria evaluation of the project pre-conceptual design identified several issues that lead to the conclusion that the project is a major modification: 1. Evaluation Criteria #3 (Change of existing process). The proposed strategy for equipping the replacement PCPs with VFDs

  14. Evaluation of PFOS-mediated neurotoxicity in rat primary neurons and astrocytes cultured separately or in co-culture.

    PubMed

    Li, Zhenwei; Liu, Qi; Liu, Chang; Li, Chunna; Li, Yachen; Li, Shuangyue; Liu, Xiaohui; Shao, Jing

    2017-02-01

    Perfluorooctane sulfonate (PFOS) is a potential neurotoxicant reported by epidemiological investigations and experimental studies, while the underlying mechanisms are still unclear. Astrocytes not only support for the construction of neurons, but also conduct neuronal functions through glutamate-glutamine cycle in astrocyte-neuron crosstalk. In the present study, the effect of PFOS exposure on rat primary hippocampal neurons or cortex astrocytes was evaluated. Then the role of the astrocytes in PFOS-induced toxic effect on neurons was explored with astrocyte-neuron co-culture system. Exposure of rat primary hippocampal neurons to PFOS has led to oxidation-antioxidation imbalance, increased apoptosis and abnormal autophagy. The adverse effect of PFOS on rat primary cortex astrocytes manifested in the form of altered extracellular glutamate and glutamine concentrations, decreased glutamine synthase activity, as well as decreased gene expression of glutamine synthase, glutamate transporters and glutamine transporters in the glutamate-glutamine cycle. Especially, the alleviation of PFOS-inhibited neurite outgrowth in neurons could be observed in astrocyte-neuron co-culture system, though the ability of astrocytes in fostering neurite outgrowth was affected by PFOS. These results indicated that both astrocytes and neurons might be the targets of PFOS-induced neurotoxicity, and astrocytes could protect against PFOS-inhibited neurite outgrowth in primary cultured neurons. Our research might render some information in explaining the mechanisms of PFOS-induced neurotoxicity.

  15. The Effective Connectivity Between the Two Primary Motor Areas in the Brain during Bilateral Tapping of Hand Fingers

    NASA Astrophysics Data System (ADS)

    Yusoff, A. N.; Hamid, K. A.

    Dynamic causal modeling (DCM) was implemented on datasets obtained from an externally-triggered finger tapping functional MRI experiment performed by 5 male and female subjects. The objective was to model the effective connectivity between two significantly activated primary motor regions (M1). The left and right hemisphere M1s are found to be effectively and bidirectionally connected to each other. Both connections are modulated by the stimulus-free contextual input. These connectivities are however not gated (influenced) by any of the two M1s, ruling out the possibility of the non-linear behavior of connections between both M1s. A dynamic causal model was finally suggested.

  16. Basolateral Cl channels in primary airway epithelial cultures.

    PubMed

    Fischer, Horst; Illek, Beate; Finkbeiner, Walter E; Widdicombe, Jonathan H

    2007-06-01

    Salt and water absorption and secretion across the airway epithelium are important for maintaining the thin film of liquid lining the surface of the airway epithelium. Movement of Cl across the apical membrane involves the CFTR Cl channel; however, conductive pathways for Cl movement across the basolateral membrane have been little studied. Here, we determined the regulation and single-channel properties of the Cl conductance (G(Cl)) in airway surface epithelia using epithelial cultures from human or bovine trachea and freshly isolated ciliated cells from the human nasal epithelium. In Ussing chamber studies, a swelling-activated basolateral G(Cl) was found, which was further stimulated by forskolin and blocked by N-phenylanthranilic acid (DPC) = sucrose > flufenamic acid = niflumic acid = glibenclamide > CdCl(2) = 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) = DIDS = ZnCl(2) > tamoxifen > 4,4'-dinitro-2,2'-stilbene-disulfonate disodium salt (DNDS). In whole cell patch-clamp experiments, three types of G(Cl) were identified: 1) a voltage-activated, DIDS- (but not Cd-) blockable and osmosensitive G(Cl); 2) an inwardly rectifying, hyperpolarization-activated and Cd-sensitive G(Cl); and 3) a forskolin-activated, linear G(Cl), which was insensitive to Cd and DIDS. In cell-attached patch-clamp recordings, the basolateral pole of isolated ciliated cells expressed three types of Cl channels: 1) an outwardly rectifying, swelling-activated Cl channel; 2) a strongly inwardly rectifying Cl channel; and 3) a forskolin-activated, low-conductance channel. We propose that, depending on the driving force for Cl across the apical membrane, basolateral Cl channels confine Cl(-) secretion or support transcellular Cl(-) absorption.

  17. Conditions for initiating Lake Victoria haplochromine (Oreochromis esculentus) primary cell cultures from caudal fin biopsies.

    PubMed

    Filice, Melissa; Lee, C; Mastromonaco, Gabriela F

    2014-10-01

    The global decline of freshwater fishes has created a need to cryopreserve biological materials from endangered species in an effort to conserve the biodiversity within this taxon. Since maternal gametes and embryos from fish are difficult to cryopreserve, somatic cells obtained from caudal fins have become an increasingly popular resource as they contain both maternal and paternal DNA ensuring valuable traits are not lost from the population. Somatic cells stored in cryobanks can be used to supplement endangered populations with genetically valuable offspring with the use of assisted reproductive technologies. However, initiating primary cell cultures from caudal fin biopsies of endangered species can be challenging as standardized protocols have not yet been developed. The objective of this study was to identify culture conditions, including antibiotic supplementation, biopsy size, and culture temperature, suitable for establishing primary cell cultures of ngege (Oreochromis esculentus), a critically endangered African cichlid. Six-millimeter caudal fin biopsies provided sufficient material to develop a primary cell culture when incubated at 25°C using standard fish cell culture medium containing 1× Primocin. Further investigation and application of these culture conditions for other endangered freshwater fishes is necessary.

  18. [Primary culture and morphologic observation of eutopic and ectopic endometrial cells from patients with endometriosis].

    PubMed

    Yu, Chao-Qin; Shi, Shu-Fang; Liu, Yu-Huan; Wang, Rui-Xia; Song, Yan-Hua; Yu, Jin

    2006-03-01

    To explore the method of primary culture for endometriotic cells and to find out the differences in morphological manifestations among endometriotic cells and eutopic endometrial cells sampled from patients with endometriosis and endometriosis-free women. Endometriotic and eutopic endometrial cells were cultured by modified method of primary culture. The endometriotic cell types were observed and differentiated under optical and electron microscopes. The success rates for culture of eutopic endometrial cells from endometriosis-free women and patients with endometriosis were 91.67% and 93.75% respectively. The success rate for culture of endometriotic cells was 75.00%. The size of endometriotic glandular cells was similar to those of eutopic endometrial glandular cells from endometriosis-free women and patients with endometriosis. The chromatin was manifold and the nucleus was augmented in the endometriotic glandular cells. The endometriotic stromal cells were smaller than the eutopic endometrial stromal cells from endometriosis-free women and patients with endometriosis. Many tiny villi and protuberances on plasma membrane could be seen in the endometriotic stromal cells. The success rate for culture of endometriotic cells can be elevated through improving the method of primary culture. The ultrastructures of endometriotic glandular and stromal cells are obviously different from those of eutopic endometrial glandular and stromal cells from endometriosis-free women and patients with endometriosis.

  19. Patient safety culture in primary care: developing a theoretical framework for practical use

    PubMed Central

    Kirk, Susan; Parker, Dianne; Claridge, Tanya; Esmail, Aneez; Marshall, Martin

    2007-01-01

    Objective Great importance has been attached to a culture of safe practice in healthcare organisations, but it has proved difficult to engage frontline staff with this complex concept. The present study aimed to develop and test a framework for making the concept of safety culture meaningful and accessible to managers and frontline staff, and facilitating discussion of ways to improve team/organisational safety culture. Setting Eight primary care trusts and a sample of their associated general practices in north west England. Methods In phase 1 a comprehensive review of the literature and a postal survey of experts helped identify the key dimensions of safety culture in primary care. Semistructured interviews with 30 clinicians and managers explored the application of these dimensions to an established theory of organisational maturity. In phase 2 the face validity and utility of the framework was assessed in 33 interviews and 14 focus groups. Results Nine dimensions were identified through which safety culture is expressed in primary care organisations. Organisational descriptions were developed for how these dimensions might be characterised at five levels of organisational maturity. The resulting framework conceptualises patient safety culture as multidimensional and dynamic, and seems to have a high level of face validity and utility within primary care. It aids clinicians' and managers' understanding of the concept of safety culture and promotes discussion within teams about their safety culture maturity. Conclusions The framework moves the agenda on from rhetoric about the importance of safety culture to a way of understanding why and how the shared values of staff working within a healthcare organisation may be operationalised to create a safe environment for patient care. PMID:17693682

  20. Hydroxylation, conjugation and sulfation of bile acids in primary monolayer cultures of rat hepatocytes

    SciTech Connect

    Princen, H.M.; Meijer, P.

    1988-08-15

    Hydroxylation of lithocholic, chenodeoxycholic, deoxycholic and cholic acids was studied in monolayers of rat hepatocytes cultured for 76 h. The majority of added lithocholic and chenodeoxycholic acids was metabolized to beta-muricholic acid (56-76%). A small part of these bile acids (9%), however, and a considerable amount of deoxycholic and cholic acids (21%) were converted into metabolites more polar than cholic acid in the first culture period. Formation of these compounds decreased during the last day of culture. Bile acids synthesized after addition of (4-/sup 14/C)-cholesterol were almost entirely (97%) sulfated and/or conjugated, predominantly with taurine (54-66%), during culture. Sulfated bile acids were mainly composed of free bile acids. The ability of hepatocytes to sulfurylate bile acids declined with culture age. Thus, rat hepatocytes in primary monolayer culture are capable to sulfurylate bile acids and to hydroxylate trihydroxylated bile acids, suggesting formation of polyhydroxylated metabolites.

  1. The control of complex finger movements by directional information flow between mesial frontocentral areas and the primary motor cortex.

    PubMed

    Boenstrup, M; Feldheim, J; Heise, K; Gerloff, C; Hummel, F C

    2014-09-01

    Complex movements require the interplay of local activation and interareal communication of sensorimotor brain regions. This is reflected in a decrease of task-related spectral power over the sensorimotor cortices and an increase in functional connectivity predominantly in the upper alpha band in the electroencephalogram (EEG). In the present study, directionality of information flow was investigated using EEG recordings to gain better understanding about the network architecture underlying the performance of complex sequential finger movements. This was assessed by means of Granger causality-derived directed transfer function (DTF). As DTF measures the influence one signal exerts on another based on a time lag between them, it allows implications to be drawn on causal relationships. To reveal causal connections between brain regions that are specifically modulated by task complexity, we contrasted the performance of right-handed sequential finger movements of different complexities (simple, scale, complex) that were either pre-learned (memorized) or novel instructed. A complexity-dependent increase in information flow from mesial frontocentral to the left motor cortex and, less pronounced, also to the right motor cortex specifically in the upper alpha range was found. Effective coupling during sequences of high complexity was larger for memorized sequences compared with novel sequences (P = 0.0037). These findings further support the role of mesial frontocentral areas in directing the primary motor cortex in the process of orchestrating complex movements and in particular learned sequences.

  2. Observing how others lift light or heavy objects: time-dependent encoding of grip force in the primary motor cortex.

    PubMed

    Alaerts, Kaat; de Beukelaar, Toon T; Swinnen, Stephan P; Wenderoth, Nicole

    2012-07-01

    During movement observation, corticomotor excitability of the observer's primary motor cortex (M1) is modulated according to the force requirements of the observed action. Here, we explored the time course of observation-induced force encoding. Force-related changes in M1-excitability were assessed by delivering transcranial magnetic stimulations at distinct temporal phases of an observed reach-grasp-lift action. Temporal changes in force-related electromyographic activity were also assessed during active movement execution. In observation conditions in which a heavy object was lifted, M1-excitability was higher compared to conditions in which a light object was lifted. Both during observation and execution, differential force encoding tended to gradually increase from the grasping phase until the late lift phase. Surprisingly, however, during observation, force encoding was already present at the early reach phase: a time point at which no visual cues on the object's weight were available to the observer. As the observer was aware that the same weight condition was presented repeatedly, this finding may indicate that prior predictions concerning the upcoming weight condition are reflected by M1 excitability. Overall, findings may provide indications that the observer's motor system represents motor predictions as well as muscular requirements to infer the observed movement goal.

  3. Effects of high-frequency repetitive transcranial magnetic stimulation of primary motor cortex on laser-evoked potentials in migraine.

    PubMed

    de Tommaso, Marina; Brighina, Filippo; Fierro, Brigida; Francesco, Vito Devito; Santostasi, Roberto; Sciruicchio, Vittorio; Vecchio, Eleonora; Serpino, Claudia; Lamberti, Paolo; Livrea, Paolo

    2010-12-01

    The aim of this study was to examine the effects of high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on subjective pain and evoked responses induced by laser stimulation (LEPs) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter-critical phase, and to compare the effects with those of non-migraine healthy controls. Thirteen migraine patients and 12 sex- and age-matched controls were evaluated. Each rTMS session consisted of 1,800 stimuli at a frequency of 5 Hz and 90% motor threshold intensity. Sham (control) rTMS was performed at the same stimulation position. The vertex LEP amplitude was reduced at the trigeminal and hand levels in the sham-placebo condition and after rTMS to a greater extent in the migraine patients than in healthy controls, while the laser pain rating was unaffected. These results suggest that HF rTMS of motor cortex and the sham procedure can both modulate pain-related evoked responses in migraine patients.

  4. Changes of Brain Connectivity in the Primary Motor Cortex After Subcortical Stroke: A Multimodal Magnetic Resonance Imaging Study.

    PubMed

    Li, Yongxin; Wang, Defeng; Zhang, Heye; Wang, Ya; Wu, Ping; Zhang, Hongwu; Yang, Yang; Huang, Wenhua

    2016-02-01

    The authors investigated the changes in connectivity networks of the bilateral primary motor cortex (M1) of subcortical stroke patients using a multimodal neuroimaging approach with antiplatelet therapy. Nineteen patients were scanned at 2 time points: before and 1 month after the treatment. The authors assessed the resting-state functional connectivity (FC) and probabilistic fiber tracking of left and right M1 of every patient, and then compared these results to the 15 healthy controls. The authors also evaluated the correlations between the neuroimaging results and clinical scores.Compared with the controls, the patients showed a significant decrease of FC in the contralateral motor cortex before treatment, and the disrupted FC was restored after treatment. The fiber tracking results in the controls indicated that the body of the corpus callosum should be the main pathway connecting the M1 and contralateral hemispheres. All patients exhibited reduced probability of structural connectivity within this pathway before treatment and which was restored after treatment. Significant correlations were also found in these patients between the connectivity results and clinical scores, which might imply that the connectivity of M1 can be used to evaluate the motor skills in stroke patients.These findings can help elucidate the neural mechanisms responsible for the brain connectivity recovery after stroke.

  5. Organization Complexity and Primary Care Providers' Perceptions of Quality Improvement Culture Within the Veterans Health Administration.

    PubMed

    Korom-Djakovic, Danijela; Canamucio, Anne; Lempa, Michele; Yano, Elizabeth M; Long, Judith A

    2016-01-01

    This study examined how aspects of quality improvement (QI) culture changed during the introduction of the Veterans Health Administration (VHA) patient-centered medical home initiative and how they were influenced by existing organizational factors, including VHA facility complexity and practice location. A voluntary survey, measuring primary care providers' (PCPs') perspectives on QI culture at their primary care clinics, was administered in 2010 and 2012. Participants were 320 PCPs from hospital- and community-based primary care practices in Pennsylvania, West Virginia, Delaware, New Jersey, New York, and Ohio. PCPs in community-based outpatient clinics reported an improvement in established processes for QI, and communication and cooperation from 2010 to 2012. However, their peers in hospital-based clinics did not report any significant improvements in QI culture. In both years, compared with high-complexity facilities, medium- and low-complexity facilities had better scores on the scales assessing established processes for QI, and communication and cooperation.

  6. Cellular Microenvironment Dictates Androgen Production by Murine Fetal Leydig Cells in Primary Culture1

    PubMed Central

    Carney, Colleen M.; Muszynski, Jessica L.; Strotman, Lindsay N.; Lewis, Samantha R.; O'Connell, Rachel L.; Beebe, David J.; Theberge, Ashleigh B.; Jorgensen, Joan S.

    2014-01-01

    ABSTRACT Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3–5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture. PMID:25143354

  7. Cellular microenvironment dictates androgen production by murine fetal Leydig cells in primary culture.

    PubMed

    Carney, Colleen M; Muszynski, Jessica L; Strotman, Lindsay N; Lewis, Samantha R; O'Connell, Rachel L; Beebe, David J; Theberge, Ashleigh B; Jorgensen, Joan S

    2014-10-01

    Despite the fact that fetal Leydig cells are recognized as the primary source of androgens in male embryos, the mechanisms by which steroidogenesis occurs within the developing testis remain unclear. A genetic approach was used to visualize and isolate fetal Leydig cells from remaining cells within developing mouse testes. Cyp11a1-Cre mice were bred to mT/mG dual reporter mice to target membrane-tagged enhanced green fluorescent protein (GFP) within steroidogenic cells, whereas other cells expressed membrane-tagged tandem-dimer tomato red. Fetal Leydig cell identity was validated using double-labeled immunohistochemistry against GFP and the steroidogenic enzyme 3beta-HSD, and cells were successfully isolated as indicated by qPCR results from sorted cell populations. Because fetal Leydig cells must collaborate with neighboring cells to synthesize testosterone, we hypothesized that the fetal Leydig cell microenvironment defined their capacity for androgen production. Microfluidic culture devices were used to measure androstenedione and testosterone production of fetal Leydig cells that were cultured in cell-cell contact within a mixed population, were isolated but remained in medium contact via compartmentalized co-culture with other testicular cells, or were isolated and cultured alone. Results showed that fetal Leydig cells maintained their identity and steroidogenic activity for 3-5 days in primary culture. Microenvironment dictated proficiency of testosterone production. As expected, fetal Leydig cells produced androstenedione but not testosterone when cultured in isolation. More testosterone accumulated in medium from mixed cultures than from compartmentalized co-cultures initially; however, co-cultures maintained testosterone synthesis for a longer time. These data suggest that a combination of cell-cell contact and soluble factors constitute the ideal microenvironment for fetal Leydig cell activity in primary culture.

  8. Short-term primary culture of epithelial cells derived from human breast tumours.

    PubMed Central

    Speirs, V.; Green, A. R.; Walton, D. S.; Kerin, M. J.; Fox, J. N.; Carleton, P. J.; Desai, S. B.; Atkin, S. L.

    1998-01-01

    As experimental models for breast cancer, most studies rely on established human breast cancer cell lines. However, many of these lines were established over 20 years ago, many from pleural effusions rather than the primary tumour, so the validity of using them as representative models is questionable. This paper describes our experiences, over a 3-year period, in establishing short-term epithelial-cell-enriched preparations from primary breast tumours based on differential centrifugation followed by culture in selective media. Epithelial cells were successfully cultured from 55% of samples, but culture success did not appear to be correlated with tumour histology, stage, grade or node status. Epithelial cell-enriched cultures were immunopositive for broad-spectrum cytokeratin and epithelial membrane antigen (EMA). Positivity for keratin 19 confirmed that the cultures contained tumour-derived cells, which additionally showed significantly higher activity of the reductive pathway of the steroid-converting enzyme 17beta-hydroxysteroid dehydrogenase type I. That the cultures contained tumour and not normal epithelial cells was further substantiated by the complete absence of the calmodulin-like gene NB-1 in tumour-derived cultures; this is only associated with normal breast epithelia. Eighty-five per cent of cultures established from oestrogen receptor (ER)-positive tumours expressed ER in vitro; this was functional in 66% of cultures, although ER-positive phenotype was gradually lost over time. In conclusion, epithelial cells can be isolated and maintained as short-term cultures from primary breast tumours irrespective of histopathological or clinical details, providing a model system with a greater biological and clinical relevance than breast cancer cell lines. Images Figure 1 Figure 2 Figure 5 Figure 7 PMID:9836473

  9. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures

    PubMed Central

    Lepsch, Lucilia B.; Planeta, Cleopatra S.; Scavone, Critoforo

    2015-01-01

    To study cocaine's toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine. PMID:26295051

  10. Primary culture of strial marginal cells of guinea pig cochlea: growth, morphologic features, and characterization.

    PubMed

    Achouche, J; Liu, D S; Tran Ba Huy, P; Huy, P T

    1991-12-01

    To further investigate the cellular mechanisms involved in the formation of endolymph, primary cultures of marginal cells of guinea pig were established. Minute explants obtained by mechanical dissociation of stria vascularis were plated on collagen type I precoated impermeable substrate in serum-free, hormone-supplemented medium. A confluent layer of epithelial-like cells was obtained within 2 weeks. The cultured cells formed domes, demonstrating that they retain some of their transepithelial properties. Polarization was also suggested by electron microscopic observation of apical microvilli and tight junctions. Immunohistochemical methods revealed that the cultured cells coexpressed cytokeratin and vimentin, demonstrating their epithelial origin, although some degree of dedifferentiation occurred. Thus, a primary culture of marginal cells can be established that may be a suitable model for an in-depth investigation of the function of the marginal cells.

  11. Cocaine Causes Apoptotic Death in Rat Mesencephalon and Striatum Primary Cultures.

    PubMed

    Lepsch, Lucilia B; Planeta, Cleopatra S; Scavone, Critoforo

    2015-01-01

    To study cocaine's toxic effects in vitro, we have used primary mesencephalic and striatal cultures from rat embryonic brain. Treatment with cocaine causes a dramatic increase in DNA fragmentation in both primary cultures. The toxicity induced by cocaine was paralleled with a concomitant decrease in the microtubule associated protein 2 (MAP2) and/or neuronal nucleus protein (NeuN) staining. We also observed in both cultures that the cell death caused by cocaine was induced by an apoptotic mechanism, confirmed by TUNEL assay. Therefore, the present paper shows that cocaine causes apoptotic cell death and inhibition of the neurite prolongation in striatal and mesencephalic cell culture. These data suggest that if similar neuronal damage could be produced in the developing human brain, it could account for the qualitative or quantitative defects in neuronal pathways that cause a major handicap in brain function following prenatal exposure to cocaine.

  12. Culturally & Linguistically Sensitive Practices in Motor Skills Intervention for Young Children. Technical Report.

    ERIC Educational Resources Information Center

    Baghwanji, Yash; Santos, Rosa Milagros; Fowler, Susan A.

    This report examines the validity of motor intervention practices that have been described as "quality" practices and the extent to which they are appropriate for all families and children. Misunderstandings and conflicts in the areas of motor skills evaluation and intervention can occur between those providing services and those receiving…

  13. Optimization of NRU assay in primary cultures of Eisenia fetida for metal toxicity assessment.

    PubMed

    Irizar, Amaia; Duarte, Daniel; Guilhermino, Lucia; Marigómez, Ionan; Soto, Manu

    2014-09-01

    Coelomocytes, immunocompetent cells of lumbricids, have received special attention for ecotoxicological studies due to their sensibility to pollutants. Their in vitro responses are commonly quantified after in vivo exposure to real or spiked soils. Alternatively, quantifications of in vitro responses after in vitro exposure are being studied. Within this framework, the present study aimed at optimizing the neutral red uptake (NRU) assay in primary culture of Eisenia fetida coelomocytes for its application in soil toxicity testing. Optimized assay conditions were: earthworm depuration for 24 h before retrieving coelomocytes by electric extrusion; 2 × 10(5) seeded cells/well (200 µl) for the NRU assay and incubation for 1 h with neutral red dye. Supplementation of the culture medium with serum was not compatible with the NRU assay, but coelomocytes could be maintained with high viability for 3 days in a serum-free medium without replenishment. Thus, primary cultures were used for 24 h in vitro toxicity testing after exposure to different concentrations of Cd, Cu, Ni and Pb (ranging from 0.1 to 100 μg/ml). Primary cultures were sensitive to metals, the viability declining in a dose-dependent manner. The toxicity rank was, from high to low, Pb > Ni > Cd > Cu. Therefore, it can be concluded that the NRU assay in coelomocytes in primary cultures provides a sensitive and prompt response after in vitro exposure to metals.

  14. Methods Development for the Isolation and Culture of Primary Corneal Endothelial Cells

    DTIC Science & Technology

    2017-02-01

    USAMRICD‐TR‐17‐02  Methods Development for the Isolation and  Culture of Primary Corneal Endothelial  Cells       Robert L. Haggins Jr...Development for the Isolation and Culture of Primary Corneal Endothelial Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...endothelial cells (CECs). If so, cellular therapy intended to replenish CECs lost to injury and age may represent an effective approach in the

  15. Health system factors affecting communication with pediatricians: gendered work culture in primary care.

    PubMed

    Lynch, Sean

    2011-01-01

    This qualitative study examined the roles that practice setting, education level, and gender may play in social workers' communication satisfaction with pediatricians. Taking an ethnographic approach, the researcher interviewed social workers and pediatricians who worked together to provide mental health services in primary care. The results suggested that gender at the health system level may be an issue and that gendered work culture in primary care was a factor in communication. In particular, reimbursement, an aspect of the gendered work culture, was a substantial communication barrier, and the implications for Medicaid billing are discussed.

  16. Motor cognitive processing speed estimation among the primary schoolchildren by deriving prediction formula: A cross-sectional study

    PubMed Central

    Aranha, Vencita Priyanka; Moitra, Monika; Saxena, Shikha; Narkeesh, Kanimozhi; Arumugam, Narkeesh; Samuel, Asir John

    2017-01-01

    Objectives: Motor cognitive processing speed (MCPS) is often reported in terms of reaction time. In spite of being a significant indicator of function, behavior, and performance, MCPS is rarely used in clinics and schools to identify kids with slowed motor cognitive processing. The reason behind this is the lack of availability of convenient formula to estimate MCPS. Thereby, the aim of this study is to estimate the MCPS in the primary schoolchildren. Materials and Methods: Two hundred and four primary schoolchildren, aged 6–12 years, were recruited by the cluster sampling method for this cross-sectional study. MCPS was estimated by the ruler drop method (RDM). By this method, a metallic stainless steel ruler was suspended vertically such that 5 cm graduation of the lower was aligned between the web space of the child's hand, and the child was asked to catch the moving ruler as quickly as possible, once released from the examiner's hand. Distance the ruler traveled was recorded and converted into time, which is the MCPS. Multiple regression analysis of variables was performed to determine the influence of independent variables on MCPS. Results: Mean MCPS of the entire sample of 204 primary schoolchildren is 230.01 ms ± 26.5 standard deviation (95% confidence interval; 226.4–233.7 ms) that ranged from 162.9 to 321.6 ms. By stepwise regression analysis, we derived the regression equation, MCPS (ms) = 279.625–5.495 × age, with 41.3% (R = 0.413) predictability and 17.1% (R2 = 0.171 and adjusted R2 = 0.166) variability. Conclusion: MCPS prediction formula through RDM in the primary schoolchildren has been established. PMID:28149087

  17. Ipsilateral corticotectal projections from the primary, premotor and supplementary motor cortical areas in adult macaque monkeys: a quantitative anterograde tracing study.

    PubMed

    Fregosi, Michela; Rouiller, Eric M

    2017-09-18

    The corticotectal projection from cortical motor areas is one of several descending pathways involved in the indirect control of spinal motoneurons. In non-human primates, previous studies reported that cortical projections to the superior colliculus (SC) originated from the premotor cortex (PM) and the primary motor cortex, whereas no projection originated from the supplementary motor area (SMA). The aim of the present study was to investigate and compare the properties of corticotectal projections originating from these three cortical motor areas in intact adult macaques (n = 9). The anterograde tracer biotinylated dextran amine was injected into one of these cortical areas in each animal. Individual axonal boutons, both en passant and terminaux, were charted and counted in the different layers of the ipsilateral SC. The data confirmed the presence of strong corticotectal projections from the PM. A new observation was that strong corticotectal projections were also found to originate from the SMA (its proper division). The corticotectal projection from the primary motor cortex was quantitatively less strong than that from either the premotor or SMAs. The corticotectal projection from each motor area was directed mainly to the deep layer of the SC, although its intermediate layer was also a consistent target of fairly dense terminations. The strong corticotectal projections from non-primary motor areas are in position to influence the preparation and planning of voluntary movements. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  18. Short-term effects of unilateral lesion of the primary motor cortex (M1) on ipsilesional hand dexterity in adult macaque monkeys.

    PubMed

    Bashir, Shahid; Kaeser, Mélanie; Wyss, Alexander; Hamadjida, Adjia; Liu, Yu; Bloch, Jocelyne; Brunet, Jean-François; Belhaj-Saif, Abderraouf; Rouiller, Eric M

    2012-01-01

    Although the arrangement of the corticospinal projection in primates is consistent with a more prominent role of the ipsilateral motor cortex on proximal muscles, rather than on distal muscles involved in manual dexterity, the role played by the primary motor cortex on the control of manual dexterity for the ipsilateral hand remains a matter a debate, either in the normal function or after a lesion. We, therefore, tested the impact of permanent unilateral motor cortex lesion on the manual dexterity of the ipsilateral hand in 11 macaque monkeys, within a time window of 60 days post-lesion. For comparison, unilateral reversible pharmacological inactivation of the motor cortex was produced in an additional monkey. Manual dexterity was assessed quantitatively based on three motor parameters derived from two reach and grasp manual tasks. In contrast to the expected dramatic, complete deficit of manual dexterity of the contralesional hand that persists for several weeks, the impact on the manual dexterity of the ipsilesional hand was generally moderate (but statistically significant) and, when present, lasted less than 20 days. Out of the 11 monkeys, only 3 showed a deficit of the ipsilesional hand for 2 of the 3 motor parameters, and 4 animals had a deficit for only one motor parameter. Four monkeys did not show any deficit. The reversible inactivation experiment yielded results consistent with the permanent lesion data. In conclusion, the primary motor cortex exerts a modest role on ipsilateral manual dexterity, most likely in the form of indirect hand postural control.

  19. Establishment of primary cell culture from the temperate symbiotic cnidarian, Anemonia viridis.

    PubMed

    Barnay-Verdier, Stéphanie; Dall'osso, Diane; Joli, Nathalie; Olivré, Juliette; Priouzeau, Fabrice; Zamoum, Thamilla; Merle, Pierre-Laurent; Furla, Paola

    2013-10-01

    The temperate symbiotic sea anemone Anemonia viridis, a member of the Cnidaria phylum, is a relevant experimental model to investigate the molecular and cellular events involved in the preservation or in the rupture of the symbiosis between the animal cells and their symbiotic microalgae, commonly named zooxanthellae. In order to increase research tools for this model, we developed a primary culture from A. viridis animal cells. By adapting enzymatic dissociation protocols, we isolated animal host cells from a whole tentacle in regeneration state. Each plating resulted in a heterogeneous primary culture consisted of free zooxanthellae and many regular, small rounded and adherent cells (of 3-5 μm diameter). Molecular analyses conducted on primary cultures, maintained for 2 weeks, confirmed a specific signature of A. viridis cells. Further serial dilutions and micromanipulation allowed us to obtain homogenous primary cultures of the small rounded cells, corresponding to A. viridis "epithelial-like cells". The maintenance and the propagation over a 4 weeks period of primary cells provide, for in vitro cnidarian studies, a preliminary step for further investigations on cnidarian cellular pathways notably in regard to symbiosis interactions.

  20. Morphology of primary human venous endothelial cell cultures before and after culture medium exchange.

    PubMed

    Krüger-Genge, A; Fuhrmann, R; Jung, F; Franke, R P

    2015-01-01

    The evaluation of the interaction of human, venous endothelial cells (HUVEC) with body foreign materials on the cellular level cannot be performed in vivo, but is investigated in vitro under standard culture conditions. To maintain the vitality, proliferation and morphology of HUVEC seeded on body foreign substrates over days, the cell culture medium is usually exchanged every second day. It is well known, that alterations in the microenvironment of cells bear the risk of influencing cell morphology and function. In the current study the influence of cell culture medium exchange on HUVEC cytoskeletal microfilament structure and function was investigated. HUVEC in the third passage were seeded on extracellular matrix (ECM) - which was secreted from bovine corneal endothelial cells on glass- until functional confluence was reached. The experiment started 11 days after HUVEC seeding with an exchange of the cell culture medium followed by a staining of the actin microfilaments with phalloidin-rhodamin 1.5 and 5 minutes after medium exchange. The microfilaments were documented by use of an Olympus microscope (IMT-2) equipped with a UV lamp and online connected to a TV chain (Sony XC 50 ST/monochrome) implying an OPTIMAS - Image analysis system. Prostacyclin was analysed in the cell culture supernatant. 1.5 min after culture medium exchange in the functionally confluent cultures a slight disturbance of the actin microfilament structure with a broadening of the marginal filament band, a partial disconnection of cell-cell contacts and the appearance of intercellular fenestrations were observed. 5 minutes after medium exchange a redevelopment of the slightly disturbed microfilament structure with a condensation and narrowing of the marginal filament band was seen. 12 h later a further consolidation of the microfilament structure occurred. In addition, a perturbation of the cultured HUVEC occurred after cell culture medium exchange. The prostacyclin concentration in the

  1. COMMUNICATION: On variability and use of rat primary motor cortex responses in behavioral task discrimination

    NASA Astrophysics Data System (ADS)

    Jensen, Winnie; Rousche, Patrick J.

    2006-03-01

    The success of a cortical motor neuroprosthetic system will rely on the system's ability to effectively execute complex motor tasks in a changing environment. Invasive, intra-cortical electrodes have been successfully used to predict joint movement and grip force of a robotic arm/hand with a non-human primate (Chapin J K, Moxon K A, Markowitz R S and Nicolelis M A L 1999 Real-time control of a robotic arm using simultaneously recorded neurons in the motor cortex Nat. Neurosci. 2 664-70). It is well known that cortical encoding occurs with a high degree of cortical plasticity and depends on both the functional and behavioral context. Questions on the expected robustness of future motor prosthesis systems therefore still remain. The objective of the present work was to study the effect of minor changes in functional movement strategies on the M1 encoding. We compared the M1 encoding in freely moving, non-constrained animals that performed two similar behavioral tasks with the same end-goal, and investigated if these behavioral tasks could be discriminated based on the M1 recordings. The rats depressed a response paddle either with a set of restrictive bars ('WB') or without the bars ('WOB') placed in front of the paddle. The WB task required changes in the motor strategy to complete the paddle press and resulted in highly stereotyped movements, whereas in the WOB task the movement strategy was not restricted. Neural population activity was recorded from 16-channel micro-wire arrays and data up to 200 ms before a paddle hit were analyzed off-line. The analysis showed a significant neural firing difference between the two similar WB and WOB tasks, and using principal component analysis it was possible to distinguish between the two tasks with a best classification at 76.6%. While the results are dependent upon a small, randomly sampled neural population, they indicate that information about similar behavioral tasks may be extracted from M1 based on relatively few

  2. Preventive effect of piracetam and vinpocetine on hypoxia-reoxygenation induced injury in primary hippocampal culture.

    PubMed

    Solanki, P; Prasad, D; Muthuraju, S; Sharma, A K; Singh, S B; Ilavzhagan, G

    2011-04-01

    The present study investigates the potential of Piracetam and Vinpocetine (nootropic drugs, known to possess neuroprotective properties) in preventing hypoxia-reoxygenation induced oxidative stress in primary hippocampal cell culture. The hippocampal culture was exposed to hypoxia (95% N(2), 5% CO(2)) for 3h and followed by 1h of reoxygenation (21% O(2) and 5% CO(2)) at 37 °C. The primary hippocampal cultures were supplemented with the optimum dose of Piracetam and Vinpocetine, independently, and the cultures were divided into six groups, viz. Control/Normoxia, Hypoxia, Hypoxia+Piracetam, Hypoxia+Vinpocetine, Normoxia + Piracetam and Normoxia+Vinpocetine. The cell-viability assays and biochemical oxidative stress parameters were evaluated for each of the six groups. Administration of 1mM Piracetam or 500 nM Vinpocetine significantly prevents the culture from hypoxia-reoxygenation injury when determined by Neutral Red assay, LDH release and Acetylcholine esterase activity. Results showed that Piracetam and Vinpocetine supplementation significantly prevented the fall of mitochondrial membrane potential, rise in ROS generation and reduction in antioxidant levels associated with the hypoxia-reoxygenation injury. In conclusion, the present study establishes that both Piracetam and Vinpocetine give neuroprotection against hypoxia-reoxygenation injury in primary hippocampal cell culture. Copyright © 2010 Elsevier Ltd. All rights reserved.

  3. Protein-engineered scaffolds for in vitro 3D culture of primary adult intestinal organoids.

    PubMed

    DiMarco, Rebecca L; Dewi, Ruby E; Bernal, Gabriela; Kuo, Calvin; Heilshorn, Sarah C

    2015-10-15

    Though in vitro culture of primary intestinal organoids has gained significant momentum in recent years, little has been done to investigate the impact of microenvironmental cues provided by the encapsulating matrix on the growth and development of these fragile cultures. In this work, the impact of various in vitro culture parameters on primary adult murine organoid formation and growth are analyzed with a focus on matrix properties and geometric culture configuration. The air-liquid interface culture configuration was found to result in enhanced organoid formation relative to a traditional submerged configuration. Additionally, through use of a recombinantly engineered extracellular matrix (eECM), the effects of biochemical and biomechanical cues were independently studied. Decreasing mechanical stiffness and increasing cell adhesivity were found to increase organoid yield. Tuning of eECM properties was used to obtain organoid formation efficiency values identical to those observed in naturally harvested collagen I matrices but within a stiffer construct with improved ease of physical manipulation. Increased ability to remodel the surrounding matrix through mechanical or enzymatic means was also shown to enhance organoid formation. As the engineering and tunability of recombinant matrices is essentially limitless, continued property optimization may result in further improved matrix performance and may help to identify additional microenvironmental cues that directly impact organoid formation, development, differentiation, and functional behavior. Continued culture of primary organoids in recombinant matrices could therefore prove to be largely advantageous in the field of intestinal tissue engineering for applications in regenerative medicine and in vitro tissue mimics.

  4. Prediction of arm trajectory from the neural activities of the primary motor cortex with modular connectionist architecture.

    PubMed

    Choi, Kyuwan; Hirose, Hideaki; Sakurai, Yoshio; Iijima, Toshio; Koike, Yasuharu

    2009-11-01

    In our previous study [Koike, Y., Hirose, H., Sakurai, Y., Iijima T., (2006). Prediction of arm trajectory from a small number of neuron activities in the primary motor cortex. Neuroscience Research, 55, 146-153], we succeeded in reconstructing muscle activities from the offline combination of single neuron activities recorded in a serial manner in the primary motor cortex of a monkey and in reconstructing the joint angles from the reconstructed muscle activities during a movement condition using an artificial neural network. However, the joint angles during a static condition were not reconstructed. The difficulties of reconstruction under both static and movement conditions mainly arise due to muscle properties such as the velocity-tension relationship and the length-tension relationship. In this study, in order to overcome the limitations due to these muscle properties, we divided an artificial neural network into two networks: one for movement control and the other for posture control. We also trained the gating network to switch between the two neural networks. As a result, the gating network switched the modules properly, and the accuracy of the estimated angles improved compared to the case of using only one artificial neural network.

  5. Low-frequency rTMS inhibitory effects in the primary motor cortex: Insights from TMS-evoked potentials.

    PubMed

    Casula, Elias P; Tarantino, Vincenza; Basso, Demis; Arcara, Giorgio; Marino, Giuliana; Toffolo, Gianna Maria; Rothwell, John C; Bisiacchi, Patrizia S

    2014-09-01

    The neuromodulatory effects of repetitive transcranial magnetic stimulation (rTMS) have been mostly investigated by peripheral motor-evoked potentials (MEPs). New TMS-compatible EEG systems allow a direct investigation of the stimulation effects through the analysis of TMS-evoked potentials (TEPs). We investigated the effects of 1-Hz rTMS over the primary motor cortex (M1) of 15 healthy volunteers on TEP evoked by single pulse TMS over the same area. A second experiment in which rTMS was delivered over the primary visual cortex (V1) of 15 healthy volunteers was conducted to examine the spatial specificity of the effects. Single-pulse TMS evoked four main components: P30, N45, P60 and N100. M1-rTMS resulted in a significant decrease of MEP amplitude and in a significant increase of P60 and N100 amplitude. There was no effect after V1-rTMS. 1-Hz rTMS appears to increase the amount of inhibition following a TMS pulse, as demonstrated by the higher N100 and P60, which are thought to originate from GABAb-mediated inhibitory post-synaptic potentials. Our results confirm the reliability of the TMS-evoked N100 as a marker of cortical inhibition and provide insight into the neuromodulatory effects of 1-Hz rTMS. The present finding could be of relevance for therapeutic and diagnostic purposes.

  6. Increased cerebellar activation after repetitive transcranial magnetic stimulation over the primary motor cortex in patients with multiple system atrophy

    PubMed Central

    Li, Linling; Wu, Tianxia; Hou, Bo; Wu, Shuang; Feng, Feng; Cui, Liying

    2016-01-01

    Background Previous review reported that the high-frequency repetitive transcranial magnetic stimulation (rTMS) over the primary motor area (M1) of Parkinson’s disease (PD) patients could alleviate their symptoms. This study aimed to investigate the effect of rTMS over the left M1 of patients with multiple system atrophy (MSA). Methods Fifteen MSA patients were randomly assigned to receive a 10-session real (EP: group of experimental patients; n=7) or sham (CP: group of control patients; n=8) rTMS stimulation over two weeks. The overall experimental procedure consisted of two functional magnetic resonance imaging (fMRI) sessions, before and after a 10-session rTMS treatment. A complex self-paced sequential tapping task was performed during fMRI scanning. In addition, 18 age and gender matched healthy controls (HC) were enrolled. Subjects from the HC group did not receive any rTMS treatment and they underwent fMRI examination only once. The primary end point was the motor score change of the Unified Multiple System Atrophy Rating Scale (UMSARS-II) measured before and after the 5th and 10th session. Task-related activation was also compared among groups. Results After active rTMS treatment, only patients of EP group significant improvement in UMSARS-II score. Compared to HC, MSA patients showed significant activation over similar brain areas except for the cerebellum. Increased activation was obtained in the bilateral cerebellum after rTMS treatment in the EP group. On the contrary, no increased activation was identified in the CP group. Conclusions Our results highlight rTMS over M1 induced motor improvement in MSA patients that may be associated with increased activation in the cerebellum. PMID:27127756

  7. Efficient and simple approach to in vitro culture of primary epithelial cancer cells

    PubMed Central

    Janik, Karolina; Popeda, Marta; Peciak, Joanna; Rosiak, Kamila; Smolarz, Maciej; Treda, Cezary; Rieske, Piotr; Stoczynska-Fidelus, Ewelina; Ksiazkiewicz, Magdalena

    2016-01-01

    Primary cancer cells constitute a favourable testing platform for in vitro research in oncology field as they reflect tumour state more accurately than the most commonly employed stable cell lines. Unfortunately, due to limited availability of material and difficulties with protocols validation, primary models are rarely implemented into laboratory practice. We have compared protocols for primary cultures, differing in media components and plate coatings. In terms of culture establishment, application of Geltrex® coating demonstrated equal efficiency to feeder layer (83% compared with 72% successfully established breast and 80% compared with 80% prostate tumour specimens), yet it was substantially less complicated and easier to validate. Both Geltrex® coating and tissue-specific primary cell medium were permanently required to successfully maintain primary epithelial prostate cancer cells (PEPCs) in culture. In case of primary epithelial breast cancer cells (PEBCs), collagen I coating enabled to obtain comparable number of passages to Geltrex® coating (P=0.438). Commercial primary cell media demonstrated lower efficiency than tissue-specific ones (PEPCs–5 compared with 8 and PEBCs–6 compared with 9 passages). Interestingly, both analysed tumour types were unsusceptible to induction of culture lifespan extension when transduced with SV40LT, BMI-1 or hEST2 genes, commonly applied as potential immortalizing agents. In conclusion, the approach based on extracellular matrix reconstitution and tissue-specific primary cell media is easy to validate and provides in vitro expansion sufficient for analytical purposes (approximately 8 passages). Therefore, it may facilitate implementation of hardly available experimental models for a variety of analyses. PMID:27803125

  8. Rapid Selection of Mesenchymal Stem and Progenitor Cells in Primary Prostate Stromal Cultures

    PubMed Central

    Brennen, W. Nathaniel; Kisteman, L. Nelleke; Isaacs, John T.

    2016-01-01

    BACKGROUND Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. METHODS Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (>25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. RESULTS MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 μm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. CONCLUSIONS Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when

  9. 9 CFR 3.15 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., Care, Treatment, and Transportation of Dogs and Cats 1 Transportation Standards § 3.15 Primary... transport dogs and cats must be designed, constructed, and maintained in a manner that at all times protects... being transported in it. (c) Each primary enclosure containing dogs or cats must be positioned in the...

  10. 9 CFR 3.15 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., Care, Treatment, and Transportation of Dogs and Cats 1 Transportation Standards § 3.15 Primary... transport dogs and cats must be designed, constructed, and maintained in a manner that at all times protects... being transported in it. (c) Each primary enclosure containing dogs or cats must be positioned in the...

  11. 9 CFR 3.15 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., Care, Treatment, and Transportation of Dogs and Cats 1 Transportation Standards § 3.15 Primary... transport dogs and cats must be designed, constructed, and maintained in a manner that at all times protects... being transported in it. (c) Each primary enclosure containing dogs or cats must be positioned in the...

  12. 9 CFR 3.15 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Care, Treatment, and Transportation of Dogs and Cats 1 Transportation Standards § 3.15 Primary... transport dogs and cats must be designed, constructed, and maintained in a manner that at all times protects... being transported in it. (c) Each primary enclosure containing dogs or cats must be positioned in the...

  13. 9 CFR 3.15 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., Care, Treatment, and Transportation of Dogs and Cats 1 Transportation Standards § 3.15 Primary... transport dogs and cats must be designed, constructed, and maintained in a manner that at all times protects... being transported in it. (c) Each primary enclosure containing dogs or cats must be positioned in the...

  14. 9 CFR 3.88 - Primary conveyances (motor vehicle, rail, air, and marine).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Care, Treatment, and Transportation of Nonhuman Primates 2 Transportation Standards § 3.88 Primary... transport nonhuman primates must be designed, constructed, and maintained in a manner that at all times... being transported in it. (c) Each primary enclosure containing nonhuman primates must be positioned...

  15. Motor Vehicle Crash Fatalities in States With Primary Versus Secondary Seat Belt Laws: A Time-Series Analysis.

    PubMed

    Lee, Lois K; Monuteaux, Michael C; Burghardt, Lindsey C; Fleegler, Eric W; Nigrovic, Lise E; Meehan, William P; Schutzman, Sara A; Mannix, Rebekah

    2015-08-04

    Motor vehicle crashes (MVCs) remain a leading cause of injury-related deaths in the United States. Primary seat belt laws allow vehicle occupants to be ticketed solely for not wearing seat belts, and secondary laws allow ticketing only for failure to wear seat belts in the setting of other violations. To determine the association between MVC fatality rates and primary versus secondary seat belt laws. Retrospective time-series analysis. United States, 2001 to 2010. MVC fatalities in occupants aged 10 years or older identified in the Fatality Analysis Reporting System. Population-based rates of fatal crashes. There were 283 183 MVC fatalities in occupants aged 10 years or older from 2001 to 2010 (overall rate, 13.0 per 100 000 persons). In 2001, the mean fatality rate was 14.6 per 100 000 persons, 16 states had primary seat belt laws, and 33 states had secondary laws. In 2010, the mean fatality rate was 9.7 per 100 000 persons, 30 states had primary seat belt laws, and 19 states had secondary laws. In the multivariate regression model, states with primary seat belt laws had lower MVC fatality rates than states with secondary laws (adjusted incidence rate ratio, 0.83 [95% CI, 0.78 to 0.90]). Only fatalities were analyzed from the database, and the degree of law enforcement could not be ascertained. States with primary seat belt laws had lower rates of MVC fatalities than those with secondary laws. Adoption of primary seat belt laws may offer optimal occupant protection. None.

  16. Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI): lessons from exploration of cultural variations in visual-motor integration performance of preschoolers.

    PubMed

    Lim, C Y; Tan, P C; Koh, C; Koh, E; Guo, H; Yusoff, N D; See, C Q; Tan, T

    2015-03-01

    Visual-motor integration (VMI) is important in children's development because it is associated with the performance of many functional skills. Deficits in VMI have been linked to difficulties in academic performance and functional tasks. Clinical assessment experience of occupational therapists in Singapore suggested that there is a potential difference between the VMI performance of Singaporean and American children. Cross-cultural studies also implied that culture has an influence on a child's VMI performance, as it shapes the activities that a child participates in. The purpose of this study was to (1) explore if there was a difference between the VMI performance of Singaporean and American preschoolers, and (2) determine if there were ethnic differences in the VMI performance of Singaporean preschoolers. The Beery-VMI, which was standardized in America, is commonly used by occupational therapists in Singapore to assess the VMI ability of children. We administered the Beery-VMI (fifth edition) full form test (excluding the supplemental tests) to 385 preschoolers (mean age = 63.3 months) from randomly selected schools in Singapore. We compared the scores of Singaporean preschoolers with those of the American standardization norms using the one-sample t-test. Scores of different ethnic groups among the Singapore population were also compared using a one-way anova, followed by the Bonferroni post-hoc test. Singaporean preschoolers and the standardization sample of American children performed significantly differently in all age groups (P < 0.05). Among the Singapore population, the scores were also significantly different (P < 0.05) between the (i) Chinese and Malay and (ii) Chinese and Indians ethnic groups. Preschoolers from different cultural and ethnic groups had different VMI performance. Certain cultural beliefs and practices may affect VMI performance. Clinicians should exercise caution when using an assessment in communities and cultures outside the ones on

  17. Cabergoline protects dopaminergic neurons against rotenone-induced cell death in primary mesencephalic cell culture.

    PubMed

    Meinel, J; Radad, K; Rausch, W-D; Reichmann, H; Gille, G

    2015-01-01

    In the present study, primary mesencephalic cell cultures prepared from embryonic mouse mesencephala were used to investigate the neuroprotective effect of cabergoline, an ergoline D2 receptor agonist, against the pesticide and neurotoxin rotenone relevant to Parkinson disease (PD). Treatment of cultures with cabergoline alone significantly increased the number of tyrosine hydroxylase immunoreactive (THir) neurons and reduced the release of lactate dehydrogenase (LDH) into the culture medium compared to untreated controls. Against rotenone toxicity, cabergoline significantly rescued degenerating THir neurons, reduced the release of LDH into the culture medium and improved the morphology of surviving THir neurons. The neuroprotective effects afforded by cabergoline were independent of dopaminergic stimulation as blocking of dopamine receptors by the dopamine receptor antagonist sulpiride did not prevent them. Furthermore, rotenone-induced formation of reactive oxygen species (ROS) was significantly reduced by cabergoline. Although cabergoline increased the glutathione (GSH) content in the culture, the protective effect for dopaminergic neurons seemed not to be predominantly mediated by increasing GSH, as depletion of GSH by L-buthionine-(S,R)-sulfoximine (BSO), a GSH biosynthesis inhibitor, did not prevent cabergoline-mediated neuroprotection of THir neurons in rotenone-treated cultures. Moreover, cabergoline significantly increased the ATP/protein ratio in primary mesencephalic cell cultures when added alone or prior to rotenone treatment. These results indicate a neuroprotective effect of cabergoline for dopaminergic neurons against rotenone toxicity. This effect was independent of dopamine receptor stimulation and was at least partially mediated by reducing ROS production and increasing the ATP/protein ratio.

  18. [Application of the cultural competence model in the experience of care in nursing professionals Primary Care].

    PubMed

    Gil Estevan, María Dolores; Solano Ruíz, María Del Carmen

    2017-06-10

    To know the experiences and perceptions of nurses in providing care and health promotion, women belonging to groups at risk of social vulnerability, applying the model of cultural competence Purnell. Phenomenological qualitative study. Department of Health Elda. A total of 22 primary care professional volunteers. Semi-structured interviews and focus groups with recording and content analysis, according to the theory model of cultural competence. Socio-cultural factors influence the relationship between professionals and users of the system. The subtle racism and historical prejudices create uncomfortable situations and mistrust. The language barrier makes it difficult not only communication, but also the monitoring and control of the health-disease process. The physical appearance and stereotypes are determining factors for primary care professionals. Although perceived misuse of health services are also talking about changes. The spiritual aspects of religious beliefs alone are taken into account in the case of Muslim women, not being considered as important in the case of Gypsy women and Romanian women. To provide quality care, consistent and culturally competent, it is necessary to develop training programs for professionals in cultural competence, to know the culture of other, and work without preconceived ideas, and ethnocentric; since the greater the knowledge of the cultural group being served, the better the quality of care provided. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  19. Use of primary cultures of Kenyon cells from bumblebee brains to assess pesticide side effects.

    PubMed

    Wilson, Daniel E; Velarde, Rodrigo A; Fahrbach, Susan E; Mommaerts, Veerle; Smagghe, Guy

    2013-09-01

    Bumblebees are important pollinators in natural and agricultural ecosystems. The latter results in the frequent exposure of bumblebees to pesticides. We report here on a new bioassay that uses primary cultures of neurons derived from adult bumblebee workers to evaluate possible side-effects of the neonicotinoid pesticide imidacloprid. Mushroom bodies (MBs) from the brains of bumblebee workers were dissected and dissociated to produce cultures of Kenyon cells (KCs). Cultured KCs typically extend branched, dendrite-like processes called neurites, with substantial growth evident 24-48 h after culture initiation. Exposure of cultured KCs obtained from newly eclosed adult workers to 2.5 parts per billion (ppb) imidacloprid, an environmentally relevant concentration of pesticide, did not have a detectable effect on neurite outgrowth. By contrast, in cultures prepared from newly eclosed adult bumblebees, inhibitory effects of imidacloprid were evident when the medium contained 25 ppb imidacloprid, and no growth was observed at 2,500 ppb. The KCs of older workers (13-day-old nurses and foragers) appeared to be more sensitive to imidacloprid than newly eclosed adults, as strong effects on KCs obtained from older nurses and foragers were also evident at 2.5 ppb imidacloprid. In conclusion, primary cultures using KCs of bumblebee worker brains offer a tool to assess sublethal effects of neurotoxic pesticides in vitro. Such studies also have the potential to contribute to the understanding of mechanisms of plasticity in the adult bumblebee brain.

  20. Antibiotic Supplements Affect Electrophysiological Properties and Excitability of Rat Hippocampal Pyramidal Neurons in Primary Culture

    PubMed Central

    Bahrami, Farideh; Janahmadi, Mahyar

    2013-01-01

    Introduction: Antibiotic supplements are regularly used in neuronal culture media to control contamination; however, they can interfere with the neuronal excitability and affect electrophysiological properties. Therefore, in this study, the effect of penicillin/streptomycin supplements on the spontaneous electrophysiological activity of hippocampal pyramidal neurons was examined. Methods: Electrophysiological whole-cell patch-clamp recordings from rat hippocampal pyramidal cells in primary culture were performed to investigate the effects of antibiotic supplements on the intrinsic excitability of cultured cells. Results: The present findings indicated that presence of antibiotic supplements (penicillin/streptomycin) in the culture medium altered the intrinsic electrical activity of hippocampal pyramidal neurons in primary culture. These alterations included: 1) depolarized resting membrane potential; 2) a significant enhancement in the after-hyperpolarization amplitude; 3) a significant increase in the area under the action potential and in the decay and rise time of the action potential; 4) a significant broadening of action potential and 5) a significant reduction in the firing frequency. Conclusion: These findings suggest that addition of antibiotic supplements to culture media influences the neuronal excitability and alters the electrophysiological properties of cultured neurons, possibly through changing the ionic conductance underlying neuronal excitability. PMID:23567852

  1. A method for establishing human primary gastric epithelial cell culture from fresh surgical gastric tissues.

    PubMed

    Aziz, Faisal; Yang, Xuesong; Wen, Qingping; Yan, Qiu

    2015-08-01

    At present, biopsy specimens, cancer cell lines and tissues obtained by gastric surgery are used in the study and analysis of gastric cancer, including the molecular mechanisms and proteomics. However, fibroblasts and other tissue components may interfere with these techniques. Therefore, the present study aimed to develop a procedure for the isolation of viable human gastric epithelial cells from gastric surgical tissues. A method was developed to culture human gastric epithelial cells using fresh, surgically excised tissues and was evaluated using immunocytochemistry, periodic acid-Schiff (PAS) staining and cell viability assays. Low cell growth was observed surrounding the gastric tissue on the seventh day of tissue explant culture. Cell growth subsequently increased, and at 12 days post-explant a high number of pure epithelial cells were detected. The gastric cancer cells exhibited rapid growth with a doubling time of 13-52 h, as compared to normal cells, which had a doubling time of 20-53 h. Immunocytochemical analyses of primary gastric cells revealed positive staining for cytokeratin 18 and 19, which indicated that the culture was comprised of pure epithelial cells and contained no fibroblasts. Furthermore, PAS staining demonstrated that the cultured gastric cells produced neutral mucin. Granulin and carbohydrate antigen 724 staining confirmed the purity of gastric cancer and normal cells in culture. This method of cell culture indicated that the gastric cells in primary culture consisted of mucin-secreting gastric epithelial cells, which may be useful for the study of gastric infection with Helicobacter pylori and gastric cancer.

  2. Production of avian influenza virus vaccine using primary cell cultures generated from host organs.

    PubMed

    Babar, Mustafeez Mujtaba; Riaz, Muhammad Suleman; Zaidi, Najam-us-Sahar Sadaf; Afzal, Farhan; Farooq, Muhammad Sabir

    2013-06-01

    The global availability of a therapeutically effective influenza virus vaccine during a pandemic remains a major challenge for the biopharmaceutical industry. Long production time, coupled with decreased supply of embryonated chicken eggs (ECE), significantly affects the conventional vaccine production. Transformed cell lines have attained regulatory approvals for vaccine production. Based on the fact that the avian influenza virus would infect the cells derived from its natural host, the viral growth characteristics were studied on chicken embryo-derived primary cell cultures. The viral propagation was determined on avian origin primary cell cultures, transformed mammalian cell lines, and in ECE. A comparison was made between these systems by utilizing various cell culture-based assays. In-vitro substrate susceptibility and viral infection characteristics were evaluated by performing hemagglutination assay (HA), 50 % tissue culture infectious dose (TCID₅₀) and monitoring of cytopathic effects (CPE) caused by the virus. The primary cell culture developed from chicken embryos showed stable growth characteristics with no contamination. HA, TCID₅₀, and CPE exhibited that these cell systems were permissive to viral infection, yielding 2-10 times higher viral titer as compared to mammalian cell lines. Though the viral output from the ECE was equivalent to the chicken cell culture, the time period for achieving it was decreased to half. Some of the prerequisites of inactivated influenza virus vaccine production include generation of higher vial titer, independence from exogenous sources, and decrease in the production time lines. Based on the tests, it can be concluded that chicken embryo primary cell culture addresses these issues and can serve as a potential alternative for influenza virus vaccine production.

  3. Nurses' perceptions of workplace culture in primary health care in Finland.

    PubMed

    Hahtela, N; Paavilainen, E; McCormack, B; Helminen, M; Slater, P; Suominen, T

    2015-12-01

    This study aimed to describe nurses' perceptions of workplace culture, especially in regard to stress levels, job satisfaction and the practice environment in primary health care. Health care is facing many challenges related to its attractiveness as a place of employment and the maintenance of a sufficient workforce supply. Previous studies report increasing rates of nurse job dissatisfaction and intentions to leave their current positions both in Finland and also globally. Improving workplace culture is thus vital in meeting the challenges related to recruitment and retention. A cross-sectional descriptive design was used to describe nurses' perceptions of workplace culture. Data were collected by questionnaire from 22 units in nine primary healthcare organizations in Finland, and analysed using descriptive and inferential statistics. Most of the respondents indicated that they were not certain whether their workplace culture was either positive or negative. Profession, age and work shift characteristics had an effect on the respondents' perceptions of workplace culture. Younger licensed practical and registered nurses assessed their workplace culture more positively, whereas older registered nurses and those working rotating rosters viewed workplace culture more negatively. The findings suggest that both unit and demographic characteristics affect workplace culture. This survey highlights that a positive workplace culture is one of the key factors in retaining and recruiting nurses, and provides an essential evidence that may be considered by other healthcare organizations. Nurse managers and healthcare leaders need to address workload management and take into account the related variables that affect a unit's workplace culture. © 2015 International Council of Nurses.

  4. Mutation in the RRM2 domain of TDP-43 in Amyotrophic Lateral Sclerosis with rapid progression associated with ubiquitin positive aggregates in cultured motor neurons.

    PubMed

    Maurel, Cindy; Madji-Hounoum, Blandine; Thepault, Rose-Anne; Marouillat, Sylviane; Brulard, Céline; Danel-Brunaud, Véronique; Camdessanche, Jean-Philippe; Blasco, Helene; Corcia, Philippe; Andres, Christian R; Vourc'h, Patrick

    2017-07-13

    Mutations in the TAR-DNA Binding Protein-43 (TDP-43) encoding the TARDBP gene are present in amyotrophic lateral sclerosis (ALS). TDP-43 is the major component of ubiquitin-positive inclusions in motor neurons in ALS patients. We report here a novel heterozygous missense mutation in TARDBP in an ALS patient presenting a rapid form of ALS. This mutation p.N259S is located within the RNA recognition motif 2 (RRM2) in very close proximity with nucleotides in RNA. It is the first time a mutation was reported in this RRM2 domain of TDP-43. Expression of TDP-43(N259S) in neuronal cells NSC-34 and in primary cultures of motor neurons was associated with cytoplasmic TDP-43/ubiquitin positive inclusions. Our findings identified for the first time a mutation in ALS in the RRM2 domain of TDP-43, reinforcing the link between this RNA-binding protein, perturbations in RNA metabolism, disruption in protein homeostasis and ALS.

  5. Subthalamic nucleus neurons are synchronized to primary motor cortex local field potentials in Parkinson’s disease

    PubMed Central

    Shimamoto, Shoichi; Ryapolova-Webb, Elena S.; Ostrem, Jill L.; Galifianakis, Nicholas B.; Miller, Kai J.; Starr, Philip A.

    2013-01-01

    In Parkinson’s disease (PD), striatal dopamine denervation results in a cascade of abnormalities in the single unit activity of downstream basal ganglia nuclei that include increased firing rate, altered firing patterns, and increased oscillatory activity. However, the effects of these abnormalities on cortical function are poorly understood. Here, in humans undergoing deep brain stimulator implantation surgery, we utilize the novel technique of subdural electrocorticography in combination with subthalamic nucleus (STN) single unit recording to study basal ganglia-cortex interactions at the millisecond time scale. We show that in patients with PD, STN spiking is synchronized with primary motor cortex (M1) local field potentials in two distinct patterns: First, STN spikes are phase-synchronized with M1 rhythms in the theta, alpha, or beta (4-30 Hz) bands. Second, STN spikes are synchronized with M1 gamma activity over a broad spectral range (50-200 Hz). The amplitude of STN spike-synchronized gamma activity in M1 is itself rhythmically modulated by the phase of a lower frequency rhythm (phase-amplitude coupling), such that “waves” of phase-synchronized gamma activity precede the occurrence of STN spikes. We show the disease specificity of these phenomena in PD, by comparison with STN-M1 paired recordings performed in a group of patients with a different disorder, primary cranio-cervical dystonia. Our findings support a model of the basal ganglia-thalamocortical loop in PD in which gamma activity in primary motor cortex, modulated by the phase of low frequency rhythms, drives STN unit discharge. PMID:23616531

  6. The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons

    PubMed Central

    Corey, Joseph M.; Gertz, Caitlyn C.; Wang, Bor-Shuen; Birrell, Lisa K.; Johnson, Sara L.; Martin, David C.; Feldman, Eva L.

    2010-01-01

    Aligned electrospun nanofibers direct neurite growth and may prove effective for repair throughout the nervous system. Applying nanofiber scaffolds to different nervous system regions will require prior in vitro testing of scaffold designs with specific neuronal and glial cell types. This would be best accomplished using primary neurons in serum-free media; however, such growth on nanofiber substrates has not yet been achieved. Here we report the development of poly(L-lactic acid) (PLLA) nanofiber substrates that support serum-free growth of primary motor and sensory neurons at low plating densities. In our study, we first compared materials used to anchor fibers to glass to keep cells submerged and maintain fiber alignment. We found that poly(lactic-co-glycolic acid) (PLGA) anchors fibers to glass and is less toxic to primary neurons than bandage and glue used in other studies. We then designed a substrate produced by electrospinning PLLA nanofibers directly on cover slips pre-coated with PLGA. This substrate retains fiber alignment even when the fiber bundle detaches from the cover slip and keeps cells in the same focal plane. To see if increasing wettability improves motor neuron survival, some fibers were plasma etched before cell plating. Survival on etched fibers was reduced at the lower plating density. Finally, the alignment of neurons grown on this substrate was equal to nanofiber alignment and surpassed the alignment of neurites from explants tested in a previous study. This substrate should facilitate investigating the behavior of many neuronal types on electrospun fibers in serum-free conditions. PMID:18396117

  7. The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons.

    PubMed

    Corey, Joseph M; Gertz, Caitlyn C; Wang, Bor-Shuen; Birrell, Lisa K; Johnson, Sara L; Martin, David C; Feldman, Eva L

    2008-07-01

    Aligned electrospun nanofibers direct neurite growth and may prove effective for repair throughout the nervous system. Applying nanofiber scaffolds to different nervous system regions will require prior in vitro testing of scaffold designs with specific neuronal and glial cell types. This would be best accomplished using primary neurons in serum-free media; however, such growth on nanofiber substrates has not yet been achieved. Here we report the development of poly(L-lactic acid) (PLLA) nanofiber substrates that support serum-free growth of primary motor and sensory neurons at low plating densities. In our study, we first compared materials used to anchor fibers to glass to keep cells submerged and maintain fiber alignment. We found that poly(lactic-co-glycolic acid) (PLGA) anchors fibers to glass and is less toxic to primary neurons than bandage and glue used in other studies. We then designed a substrate produced by electrospinning PLLA nanofibers directly on cover slips pre-coated with PLGA. This substrate retains fiber alignment even when the fiber bundle detaches from the cover slip and keeps cells in the same focal plane. To see if increasing wettability improves motor neuron survival, some fibers were plasma etched before cell plating. Survival on etched fibers was reduced at the lower plating density. Finally, the alignment of neurons grown on this substrate was equal to nanofiber alignment and surpassed the alignment of neurites from explants tested in a previous study. This substrate should facilitate investigating the behavior of many neuronal types on electrospun fibers in serum-free conditions.

  8. GABA and Glutamate in Children with Primary Complex Motor Stereotypies: A 1H MRS Study at 7T

    PubMed Central

    Harris, A. D.; Singer, H. S.; Horska, A.; Kline, T.; Ryan, M.; Edden, R. A. E.; Mahone, E. Mark

    2015-01-01

    Background and Purpose Complex motor stereotypies (CMS) are rhythmic, repetitive, fixed, purposeful but purposeless movements that stop with distraction. They can occur in otherwise normal healthy children (primary stereotypies), as well in those with autism spectrum disorders (secondary stereotypies). The underlying neurobiological basis for these movements is unknown, but thought to involve cortical-striatal-thalamo-cortical pathways. In order to further clarify potential neurochemical alterations, GABA, glutamate (Glu), glutamine (Gln), N-acetyl aspartate (NAA) and choline (Cho) levels were measured in four frontostriatal regions, using 1H MRS at 7T. Materials and Methods A total of 18 children with primary CMS and 24 typically developing controls, ages 5-10 years completed MRS at 7T. Single voxel STEAM acquisitions from the anterior cingulate cortex (ACC), premotor cortex (PMC), dorsolateral prefrontal cortex (DLPFC) and striatum were obtained and metabolites were quantified with respect to creatine using LCModel. Results The 7T scan was well tolerated by all participants. Compared to controls, children with CMS had lower levels of GABA ACC (GABA/Cr, p=0.049; GABA/Glu: p=0.051) and striatum (GABA/Cr: p= 0.028; GABA/Glu: p=0.0037), but not the DLPFC or PMC. Glu, Gln, NAA, and Cho levels did not differ between groups in any of the aforementioned regions. Within the CMS group, reduced GABA/Cr in the ACC was significantly associated with greater severity of motor stereotypies (r=-0.59, p= 0.021). Conclusions These results suggest possible GABAergic dysfunction within corticostriatal pathways in children with primary CMS. PMID:26542237

  9. Knowing in Primary Physical Education in the UK: Negotiating Movement Culture

    ERIC Educational Resources Information Center

    Ward, Gavin; Quennerstedt, Mikael

    2015-01-01

    This paper aims to understand how pupils and teachers actions-in-context constitute being-a-pupil and being-a-teacher within a primary school physical education (PE) movement culture. Dewey and Bentley's theory of transaction, which views organism-in-environment-as-a-whole, enables the researcher to explore how actions-in-ongoing activities…

  10. Resource and Production, A Primary Unit in Cultural Geography. Pupil Text and Workbook and Teacher Manual.

    ERIC Educational Resources Information Center

    Imperatore, William

    This is an instructional unit in cultural geography for the primary grades. The major objective of the unit, which is comprised of a Pupil Text/Workbook and Teacher Manual, is to develop the geographic concepts labeled resource and production. Teaching strategies used include the Pestalozzian method of asking leading questions to draw the students…

  11. CHANGES IN GENE EXPRESSION DURING DIFFERENTIATION OF CULTURED HUMAN PRIMARY BRONCHIAL EPITHELIAL CELLS

    EPA Science Inventory

    Primary airway epithelial cell cultures are a useful tool for the in vitro study of normal bronchial cell differentiation and function, airway disease mechanisms, and pathogens and toxin response. Growth of these cells at an air-liquid interface for several days results in the f...

  12. Cationic Amino Acid Based Lipids as Effective Nonviral Gene Delivery Vectors for Primary Cultured Neurons

    PubMed Central

    2013-01-01

    The delivery of specific genes into neurons offers a potent approach for treatment of diseases as well as for the study of neuronal cell biology. Here we investigated the capabilities of cationic amino acid based lipid assemblies to act as nonviral gene delivery vectors in primary cultured neurons. An arginine-based lipid, Arg-C3-Glu2C14, and a lysine-based lipid, Lys-C3-Glu2C14, with two different types of counterion, chloride ion (Cl–) and trifluoroacetic acid (TFA–), were shown to successfully mediate transfection of primary cultured neurons with plasmid DNA encoding green fluorescent protein. Among four types of lipids, we optimized their conditions such as the lipid-to-DNA ratio and the amount of pDNA and conducted a cytotoxicity assay at the same time. Overall, Arg-C3-Glu2C14 with TFA– induced a rate of transfection in primary cultured neurons higher than that of Lys-C3-Glu2C14 using an optimal weight ratio of lipid-to-plasmid DNA of 1. Moreover, it was suggested that Arg-C3-Glu2C14 with TFA– showed the optimized value higher than that of Lipofectamine2000 in experimental conditions. Thus, Arg-C3-Glu2C14 with TFA– is a promising candidate as a reliable transfection reagent for primary cultured neurons with a relatively low cytotoxicity. PMID:24087930

  13. Cultures of Engagement in Challenging Circumstances: Four Lebanese Primary Schools in Urban Beirut

    ERIC Educational Resources Information Center

    Nabhani, Mona; Busher, Hugh; Bahous, Rima

    2012-01-01

    This study of four private primary schools in Beirut, Lebanon, investigated why the children in the schools appeared to out-perform their peers in other schools. The study investigated the cultures that teachers and principals constructed in schools with children and their parents, wondering whether they would exhibit characteristics said to…

  14. Resource and Production, A Primary Unit in Cultural Geography. Pupil Text and Workbook and Teacher Manual.

    ERIC Educational Resources Information Center

    Imperatore, William

    This is an instructional unit in cultural geography for the primary grades. The major objective of the unit, which is comprised of a Pupil Text/Workbook and Teacher Manual, is to develop the geographic concepts labeled resource and production. Teaching strategies used include the Pestalozzian method of asking leading questions to draw the students…

  15. Promoting Cultural Understandings through Song across the Tasman: Pre-Service Primary Teacher Education

    ERIC Educational Resources Information Center

    Joseph, Dawn; Trinick, Robyn

    2016-01-01

    As tertiary music educators across the Tasman we argue that music, particularly song, is an effective medium for teaching and learning about non-western music when preparing generalist primary Pre-Service Teachers (PSTs). Using "voice" as a portable and accessible vehicle to transmit cultural understandings, we draw on the Zimbabwean…

  16. Culturally Relevant Literature: What Matters Most to Primary-Age Urban Learners

    ERIC Educational Resources Information Center

    Cartledge, Gwendolyn; Keesey, Susan; Bennett, Jessica G.; Ramnath, Rajiv; Council, Morris R., III.

    2016-01-01

    The ratings and rationales primary-age urban learners gave culturally relevant reading passages was the focus of this descriptive study. First- and second-grade students each read 30 researcher-developed passages reflecting the students' immediate and historical backgrounds. The students rated the passages and gave a reason for their ratings. A…

  17. Development of Quality Assurance System in Culture and Nation Character Education in Primary Education in Indonesia

    ERIC Educational Resources Information Center

    Susilana, Rudi; Asra

    2013-01-01

    The purpose of national education is to develop skills and build dignified national character and civilization in educating nation life (Act No. 20, 2003). The paper describes a system of quality assurance in culture and character education in primary education. This study employs the six sigma model which consists of the formula DMAIC (Define,…

  18. Promoting Cultural Understandings through Song across the Tasman: Pre-Service Primary Teacher Education

    ERIC Educational Resources Information Center

    Joseph, Dawn; Trinick, Robyn

    2016-01-01

    As tertiary music educators across the Tasman we argue that music, particularly song, is an effective medium for teaching and learning about non-western music when preparing generalist primary Pre-Service Teachers (PSTs). Using "voice" as a portable and accessible vehicle to transmit cultural understandings, we draw on the Zimbabwean…

  19. Knowing in Primary Physical Education in the UK: Negotiating Movement Culture

    ERIC Educational Resources Information Center

    Ward, Gavin; Quennerstedt, Mikael

    2015-01-01

    This paper aims to understand how pupils and teachers actions-in-context constitute being-a-pupil and being-a-teacher within a primary school physical education (PE) movement culture. Dewey and Bentley's theory of transaction, which views organism-in-environment-as-a-whole, enables the researcher to explore how actions-in-ongoing activities…

  20. Culturally Relevant Literature: What Matters Most to Primary-Age Urban Learners

    ERIC Educational Resources Information Center

    Cartledge, Gwendolyn; Keesey, Susan; Bennett, Jessica G.; Ramnath, Rajiv; Council, Morris R., III.

    2016-01-01

    The ratings and rationales primary-age urban learners gave culturally relevant reading passages was the focus of this descriptive study. First- and second-grade students each read 30 researcher-developed passages reflecting the students' immediate and historical backgrounds. The students rated the passages and gave a reason for their ratings. A…

  1. Primary-Grade Students' Knowledge and Thinking about Shelter as a Cultural Universal.

    ERIC Educational Resources Information Center

    Brophy, Jere; Alleman, Janet

    The traditional K-3 social studies curriculum has focused on food, clothing, shelter, communication, transportation, and other cultural universals. A study was designed to provide information with respect to the topic of shelter, and in the process, to assess claims that primary grade students do not need instruction in the topic because they…

  2. CHANGES IN GENE EXPRESSION DURING DIFFERENTIATION OF CULTURED HUMAN PRIMARY BRONCHIAL EPITHELIAL CELLS

    EPA Science Inventory

    Primary airway epithelial cell cultures are a useful tool for the in vitro study of normal bronchial cell differentiation and function, airway disease mechanisms, and pathogens and toxin response. Growth of these cells at an air-liquid interface for several days results in the f...

  3. Reusable Solid Rocket Motor - Accomplishments, Lessons, and a Culture of Success

    NASA Technical Reports Server (NTRS)

    Moore, Dennis R.; Phelps, Willie J.

    2011-01-01

    The Reusable Solid Rocket Motor represents the largest solid rocket motor ever flown and the only human rated solid motor. Each Reusable Solid Rocket Motor (RSRM) provides approximately 3-million lb of thrust to lift the integrated Space Shuttle vehicle from the launch pad. The motors burn out approximately 2 minutes later, separate from the vehicle and are recovered and refurbished. The size of the motor and the need for high reliability were challenges. Thrust shaping, via shaping of the propellant grain, was needed to limit structural loads during ascent. The motor design evolved through several block upgrades to increase performance and to increase safety and reliability. A major redesign occurred after STS-51L with the Redesigned Solid Rocket Motor. Significant improvements in the joint sealing systems were added. Design improvements continued throughout the Program via block changes with a number of innovations including development of low temperature o-ring materials and incorporation of a unique carbon fiber rope thermal barrier material. Recovery of the motors and post flight inspection improved understanding of hardware performance, and led to key design improvements. Because of the multidecade program duration material obsolescence was addressed, and requalification of materials and vendors was sometimes needed. Thermal protection systems and ablatives were used to protect the motor cases and nozzle structures. Significant understanding of design and manufacturing features of the ablatives was developed during the program resulting in optimization of design features and processing parameters. The project advanced technology in eliminating ozone-depleting materials in manufacturing processes and the development of an asbestos-free case insulation. Manufacturing processes for the large motor components were unique and safety in the manufacturing environment was a special concern. Transportation and handling approaches were also needed for the large

  4. Rat Sertoli cells acquire a beta-adrenergic response during primary culture.

    PubMed Central

    Kierszenbaum, A L; Spruill, W A; White, M G; Tres, L L; Perkins, J P

    1985-01-01

    Two-dimensional polyacrylamide gel electrophoresis and the radioligand (-)-[125I]iodopindolol (125I-Pin) have been used to study isoproterenol-dependent protein phosphorylation and beta-adrenergic receptor availability, respectively, in cultured Sertoli cells and freshly isolated seminiferous tubular segments of sexually immature and mature rats. Sertoli cells prepared from sexually immature rats show progressive 125I-Pin binding in primary cultures that correlates with isoproterenol-induced cell shape changes, redistribution of immunoreactive vimentin, and phosphorylation of this intermediate filament protein. The development of 125I-Pin binding to Sertoli cell lysates is blocked by cycloheximide. Seminiferous tubules do not show significant isoproterenol-dependent vimentin phosphorylation nor 125I-Pin binding. However, vimentin phosphorylation can be induced by follicle-stimulating hormone or a cyclic nucleotide analog. This study stresses the need for correlating pharmacological-induced responses observed in Sertoli cell primary cultures with those in the intact seminiferous tubule. Images PMID:2984678

  5. Managing change in the culture of general practice: qualitative case studies in primary care trusts.

    PubMed

    Marshall, Martin N; Mannion, Russell; Nelson, Elizabeth; Davies, Huw T O

    2003-09-13

    To explore the potential tension between the need for managers to produce measurable change and the skills required to produce cultural change, and to investigate how managers of primary care trusts are attempting to deal with this tension. Qualitative case studies using data derived from semistructured interviews and a review of published documents. An established cultural framework was to used to help interpret the findings. Six primary care trusts in England purposefully sampled to represent a range of cultural, structural, geographical, and demographic characteristics. 42 interviews with 39 different senior and middle primary care trust managers conducted over an 18 month period. We found two distinct and polarised styles of management. One group of managers adopts a directive style and challenges the prevailing norms and values of clinicians, an approach characteristically seen in organisations with hierarchical cultures. This group is made up mostly of senior managers who are driven principally by the imperative to deliver a political agenda. Managers in the second group are more inclined to work with the prevailing cultures found in general practice, attempting to facilitate change from within rather than forcing change from outside. This management style is characteristically seen in organisations with a clan-type culture. The approach was manifest mostly by middle managers, who seem to act as buffers between the demands of senior managers and their own perception of the ability and willingness of health professionals to cope with change. The different management approaches can lead to tension and dysfunction between tiers of management. The development of primary care depends on high quality managers who are able to draw on a range of different management skills and styles. Managers are most likely to be effective if they appreciate the merits and drawbacks of their different styles and are willing to work in partnership.

  6. Prolactin mediates neuroprotection against excitotoxicity in primary cell cultures of hippocampal neurons via its receptor.

    PubMed

    Vergara-Castañeda, E; Grattan, D R; Pasantes-Morales, H; Pérez-Domínguez, M; Cabrera-Reyes, E A; Morales, T; Cerbón, M

    2016-04-01

    Recently it has been reported that prolactin (PRL) exerts a neuroprotective effect against excitotoxicity in hippocampus in the rat in vivo models. However, the exact mechanism by which PRL mediates this effect is not completely understood. The aim of our study was to assess whether prolactin exerts neuroprotection against excitotoxicity in an in vitro model using primary cell cultures of hippocampal neurons, and to determine whether this effect is mediated via the prolactin receptor (PRLR). Primary cell cultures of rat hippocampal neurons were used in all experiments, gene expression was evaluated by RT-qPCR, and protein expression was assessed by Western blot analysis and immunocytochemistry. Cell viability was assessed by using the MTT method. The results demonstrated that PRL treatment of neurons from primary cultures did not modify cell viability, but that it exerted a neuroprotective effect, with cells treated with PRL showing a significant increase of viability after glutamate (Glu)--induced excitotoxicity as compared with neurons treated with Glu alone. Cultured neurons expressed mRNA for both PRL and its receptor (PRLR), and both PRL and PRLR expression levels changed after the excitotoxic insult. Interestingly, the PRLR protein was detected as two main isoforms of 100 and 40 kDa as compared with that expressed in hypothalamic cells, which was present only as a 30 kDa variant. On the other hand, PRL was not detected in neuron cultures, either by western blot or by immunohistochemistry. Neuroprotection induced by PRL was significantly blocked by specific oligonucleotides against PRLR, thus suggesting that the PRL role is mediated by its receptor expressed in these neurons. The overall results indicated that PRL induces neuroprotection in neurons from primary cell cultures.

  7. Successful establishment of primary small airway cell cultures in human lung transplantation

    PubMed Central

    2009-01-01

    Background The study of small airway diseases such as post-transplant bronchiolitis obliterans syndrome (BOS) is hampered by the difficulty in assessing peripheral airway function either physiologically or directly. Our aims were to develop robust methods for sampling small airway epithelial cells (SAEC) and to establish submerged SAEC cultures for downstream experimentation. Methods SAEC were obtained at 62 post-transplant bronchoscopies in 26 patients using radiologically guided bronchial brushings. Submerged cell cultures were established and SAEC lineage was confirmed using expression of clara cell secretory protein (CCSP). Results The cell yield for SAEC (0.956 ± 0.063 × 106) was lower than for large airway cells (1.306 ± 0.077 × 106) but did not significantly impact on the culture establishment rate (79.0 ± 5.2% vs. 83.8 ± 4.7% p = 0.49). The presence of BOS significantly compromised culture success (independent of cell yield) for SAEC (odds ratio (95%CI) 0.067 (0.01-0.40)) but not LAEC (0.3 (0.05-1.9)). Established cultures were successfully passaged and expanded. Conclusion Primary SAEC can be successfully obtained from human lung transplant recipients and maintained in culture for downstream experimentation. This technique will facilitate the development of primary in vitro models for BOS and other diseases with a small airway component such as asthma, cystic fibrosis and COPD. PMID:19857270

  8. Circadian Rhythms of PER2::LUC in Individual Primary Mouse Hepatocytes and Cultures

    PubMed Central

    Molyneux, Penny C.; Yu, Jimmy K.; Li, Alexander S.; Leise, Tanya L.; Harrington, Mary E.

    2014-01-01

    Background Hepatocytes, the parenchymal cells of the liver, express core clock genes, such as Period2 and Cryptochrome2, which are involved in the transcriptional/translational feedback loop of the circadian clock. Whether or not the liver is capable of sustaining rhythms independent of a central pacemaker is controversial. Whether and how circadian information may be shared among cells in the liver in order to sustain oscillations is currently unknown. Results In this study we isolated primary hepatocytes from transgenic Per2Luc mice and used bioluminescence as a read-out of the state of the circadian clock. Hepatocytes cultured in a collagen gel sandwich configuration exhibited persistent circadian rhythms for several weeks. The amplitude of the rhythms damped, but medium changes consistently reset the phase and amplitude of the cultures. Cry2−/− Per2Luc cells oscillated robustly and expressed a longer period. Co-culturing with wildtype cells did not significantly shorten the period, indicating that coupling among hepatocytes is insufficient to synchronize cells with significantly differing periods. However, spatial patterns revealed by cellular imaging of wildtype cultures provided evidence of weak local coupling among the hepatocytes. Conclusions Our results with primary hepatocyte cultures demonstrate that cultured hepatocytes are weakly coupled. While this coupling is not sufficient to sustain global synchrony, it does increase local synchrony, which may stabilize the circadian rhythms of peripheral oscillators, such as the liver, against noise in the entraining signals. PMID:24498336

  9. Primary cell cultures from sea urchin ovaries: a new experimental tool.

    PubMed

    Mercurio, Silvia; Di Benedetto, Cristiano; Sugni, Michela; Candia Carnevali, M Daniela

    2014-02-01

    In the present work, primary cell cultures from ovaries of the edible sea urchin Paracentrotus lividus were developed in order to provide a simple and versatile experimental tool for researches in echinoderm reproductive biology. Ovary cell phenotypes were identified and characterized by different microscopic techniques. Although cell cultures could be produced from ovaries at all stages of maturation, the cells appeared healthier and viable, displaying a higher survival rate, when ovaries at early stages of gametogenesis were used. In terms of culture medium, ovarian cells were successfully cultured in modified Leibovitz-15 medium, whereas poor results were obtained in minimum essential medium Eagle and medium 199. Different substrates were tested, but ovarian cells completely adhered only on poly-L-lysine. To improve in vitro conditions and stimulate cell proliferation, different serum-supplements were tested. Fetal calf serum and an originally developed pluteus extract were detrimental to cell survival, apparently accelerating processes of cell death. In contrast, cells cultured with sea urchin egg extract appeared larger and healthier, displaying an increased longevity that allowed maintaining them for up to 1 month. Overall, our study provides new experimental bases and procedures for producing successfully long-term primary cell cultures from sea urchin ovaries offering a good potential to study echinoid oogenesis in a controlled system and to investigate different aspects of echinoderm endocrinology and reproductive biology.

  10. Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes

    SciTech Connect

    Henkens, Tom . E-mail: Tom.Henkens@vub.ac.be; Papeleu, Peggy; Elaut, Greetje; Vinken, Mathieu; Rogiers, Vera; Vanhaecke, Tamara

    2007-01-01

    Histone deacetylase inhibitors (HDI) have been shown to increase differentiation-related gene expression in several tumor-derived cell lines by hyperacetylating core histones. Effects of HDI on primary cultured cells, however, have hardly been investigated. In the present study, the ability of trichostatin A (TSA), a prototype hydroxamate HDI, to counteract the loss of liver-specific functions in primary rat hepatocyte cultures has been investigated. Upon exposure to TSA, it was found that the cell viability of the cultured hepatocytes and their albumin secretion as a function of culture time were increased. TSA-treated hepatocytes also better maintained cytochrome P450 (CYP)-mediated phase I biotransformation capacity, whereas the activity of phase II glutathione S-transferases (GST) was not affected. Western blot and qRT-PCR analysis of CYP1A1, CYP2B1 and CYP3A11 protein and mRNA levels, respectively, further revealed that TSA acts at the transcriptional level. In addition, protein expression levels of the liver-enriched transcription factors (LETFs) hepatic nuclear factor 4 alpha (HNF4{alpha}) and CCAAT/enhancer binding protein alpha (C/EBP{alpha}) were accordingly increased by TSA throughout culture time. In conclusion, these findings indicate that TSA plays a major role in the preservation of the differentiated hepatic phenotype in culture. It is suggested that the effects of TSA on CYP gene expression are mediated via controlling the expression of LETFs.

  11. Fibrin promotes development and function of macaque primary follicles during encapsulated three-dimensional culture.

    PubMed

    Xu, J; Lawson, M S; Yeoman, R R; Molskness, T A; Ting, A Y; Stouffer, R L; Zelinski, M B

    2013-08-01

    Does fibrin introduced into the extracellular matrix affect the growth and maturation of individual primate follicles during encapsulated three-dimensional (3D) culture? While not altering follicle survival, fibrin-alginate (FIBRIN) improves macaque primary, but not secondary, follicle development during encapsulated 3D culture in terms of growth, steroidogenesis, anti-Müllerian hormone (AMH)/vascular endothelial growth factor (VEGF) production and oocyte maturation. Efforts to grow non-human primate ovarian follicles from the secondary to the antral stage during encapsulated 3D culture have been successful. However, the growth and maturation of primary follicles in vitro has not been reported in primates, especially in chemically defined conditions. In vitro follicle maturation was investigated using the rhesus macaque (Macaca mulatta). Ovaries (n = 7 pairs) were obtained during the early follicular phase of the menstrual cycle (cycle day 1-4). Primary (80-120 µm diameter) and secondary (125-225 µm diameter) follicles were isolated mechanically, randomly assigned to experimental groups, encapsulated into alginate (0.25% w/v) or FIBRIN (25 mg/ml fibrinogen-0.25% alginate) and cultured for 13 and 5 weeks, respectively. Individual follicles were cultured in alpha minimum essential medium supplemented with FSH. Follicle survival and growth were assessed by microscopy. Follicles that reached the antral stage were treated with recombinant hCG. Metaphase II (MII) oocytes were inseminated via ICSI. Follicle morphology was evaluated by hematoxylin and eosin (H&E) staining. Immunohistochemistry was performed for cytochrome P450 family 17 subfamily A polypeptide 1 (CYP17A1) and 19 subfamily A polypeptide 1 (CYP19A1). Culture medium was analyzed for estradiol (E2) and progesterone by chemiluminescence, androstenedione (A4) by radioimmunoassay, as well as anti-Müllerian hormone (AMH) and vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay. A

  12. Early oxidative damage in primary cultured trout hepatocytes: a time course study.

    PubMed

    Ferraris, Michela; Radice, Sonia; Catalani, Paolo; Francolini, Maura; Marabini, Laura; Chiesara, Enzo

    2002-09-24

    The aim of this study was to evaluate the influence of the two-step hepatocyte isolation procedure on primary cultured trout (Oncorhynchus mykiss) hepatocytes over time. We characterised the possible changes of a variety of some cellular parameters within the first 24-48 h after seeding. We followed the time dependent changes of these parameters during subsequent culture times in order to see if the cells maintained a differentiated status. Scanning electron microscopy revealed bleb formation and 20% cell damage in freshly isolated hepatocytes. During subsequent culture times the bleb dimension appear to be reduced. Heat shock proteins 70 and 50 (HSP70, HSP50) were induced by hepatocyte isolation. During the first 4 h of culture, the hepatocytes showed a variation in mitochondrial activity, an increase in free radical species (ROS), and a decrease in both glutathione (GSH) content and catalase (CAT) activity; the generation of free radicals led to an increase in the formation of 8-hydroxydeoxyguanosine (8-OHdG) in the DNA. The cells showed detectable ethoxyresorufin-O-deethylase activity after 4 h of culture, which had rapidly increased by the 24th hour. After 24 h, mitochondrial and CAT activity, free radical production, and the content of GSH and 8-OHdG returned to their original levels. P450 activity was retained for at least 48 h after seeding. Our data show that trout hepatocytes suffer significant cell injury as a result of the isolation procedure, but primary cultured cells metabolically recover from this stress after a few hours: they are capable of repairing their damaged surfaces, recovering their antioxidant defences and retaining their ability to repair DNA. Our results also confirm that trout hepatocytes in a primary culture maintain their in vivo-like metabolic activities for 3-8 days.

  13. Final report for measurement of primary particulate matter emissions from light-duty motor vehicles

    SciTech Connect

    Norbeck, J. M.; Durbin, T. D.; Truex, T. J.

    1998-12-31

    This report describes the results of a particulate emissions study conducted at the University of California, Riverside, College of Engineering-Center for Environmental Research and Technology (CE-CERT) from September of 1996 to August of 1997. The goal of this program was to expand the database of particulate emissions measurements from motor vehicles to include larger numbers of representative in-use vehicles. This work was co-sponsored by the Coordinating Research Council (CRC), the South Coast Air Quality Management District (SCAQMD), and the National Renewable Energy Laboratory (NREL) and was part of a larger study of particulate emissions being conducted in several states under sponsorship by CRC. For this work, FTP particulate mass emission rates were determined for gasoline and diesel vehicles, along with the fractions of particulates below 2.5 and 10 microns aerodynamic diameter. A total of 129 gasoline-fueled vehicles and 19 diesel-fueled vehicles were tested as part of the program.

  14. Effect of 30 Hz theta burst transcranial magnetic stimulation on the primary motor cortex in children and adolescents

    PubMed Central

    Pedapati, Ernest V.; Gilbert, Donald L.; Horn, Paul S.; Huddleston, David A.; Laue, Cameron S.; Shahana, Nasrin; Wu, Steve W.

    2015-01-01

    Fourteen healthy children (13.8 ± 2.2 years, range 10–16; M:F = 5:9) received 30 Hz intermittent theta burst transcranial magnetic stimulation (iTBS) with a stimulation intensity of 70% of resting motor threshold (RMT) with a total of 300 (iTBS300) pulses. All volunteers were free of neurologic, psychiatric and serious medical illnesses, not taking any neuropsychiatric medications, and did not have any contraindications to transcranial magnetic stimulation. Changes in the mean amplitudes of motor-evoked potentials from baseline following iTBS were expressed as a ratio and assessed from 1 to 10 min (BLOCK1) and 1–30 min (BLOCK2) using repeated-measures analysis of variance. All 14 subjects completed iTBS300 over the dominant primary motor cortex (M1) without any clinically reported adverse events. ITBS300 produced significant M1 facilitation [F(5, 65) = 3.165, p = 0.01] at BLOCK1 and trend level M1 facilitation at BLOCK2 [F(10, 129) = 1.69, p = 0.089]. Although iTBS300 (stimulation duration of 92 s at 70% RMT) delivered over M1 in typically developed children was well-tolerated and produced on average significant facilitatory changes in cortical excitability, the post-iTBS300 neurophysiologic response was variable in our small sample. ITBS300-induced changes may represent a potential neuroplastic biomarker in healthy children and those with neuro-genetic or neuro-psychiatric disorders. However, a larger sample size is needed to address safety and concerns of response variability. PMID:25762919

  15. Reorganization of the primary motor cortex following lower-limb amputation for vascular disease: a pre-post-amputation comparison.

    PubMed

    Hordacre, Brenton; Bradnam, Lynley V; Crotty, Maria

    2017-08-01

    This study compared bilateral corticomotor and intracortical excitability of the primary motor cortex (M1), pre- and post-unilateral transtibial amputation. Three males aged 45, 55, and 48 years respectively who were scheduled for elective amputation and thirteen (10 male, 3 female) healthy control participants aged 58.9 (SD 9.8) were recruited. Transcranial magnetic stimulation assessed corticomotor and intracortical excitability of M1 bilaterally. Neurophysiological assessments were performed 10 (SD 7) days prior to surgery and again at 10 (SD 3) days following surgery. Data were analyzed descriptively and objectively compared to 95% confidence intervals from control data. Prior to amputation, all three patients demonstrated stronger short-latency intracortical inhibition evoked from M1 ipsilateral to the affected limb and reduced long-latency intracortical inhibition evoked from M1 contralateral to the affected limb compared to control subjects. Following amputation, short-latency intracortical inhibition was reduced in both M1s and long-latency intracortical inhibition was reduced for the ipsilateral M1. Single-pulse motor evoked potential amplitude and motor thresholds were similar pre-to-post amputation. Modulation of intracortical excitability shortly following amputation indicates that the cortical environment may be optimized for reorganization in the acute post-amputation period which might be significant for learning to support prosthetic mobility. Implications for Rehabilitation Amputation of a lower-limb is associated with extensive reorganization at the level of the cortex. Reorganization occurs in the acute post-amputation period implying a favorable cortical environment for recovery. Rehabilitation or brain interventions may target the acute pre-prosthetic post-amputation period to optimize recovery.

  16. Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability.

    PubMed

    Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

    2017-01-01

    Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability.

  17. Timing-dependent modulation of the posterior parietal cortex–primary motor cortex pathway by sensorimotor training

    PubMed Central

    Jin, Seung-Hyun; Joutsen, Atte; Poston, Brach; Aizen, Joshua; Ellenstein, Aviva; Hallett, Mark

    2012-01-01

    Interplay between posterior parietal cortex (PPC) and ipsilateral primary motor cortex (M1) is crucial during execution of movements. The purpose of the study was to determine whether functional PPC–M1 connectivity in humans can be modulated by sensorimotor training. Seventeen participants performed a sensorimotor training task that involved tapping the index finger in synchrony to a rhythmic sequence. To explore differences in training modality, one group (n = 8) learned by visual and the other (n = 9) by auditory stimuli. Transcranial magnetic stimulation (TMS) was used to assess PPC–M1 connectivity before and after training, whereas electroencephalography (EEG) was used to assess PPC–M1 connectivity during training. Facilitation from PPC to M1 was quantified using paired-pulse TMS at conditioning-test intervals of 2, 4, 6, and 8 ms by measuring motor-evoked potentials (MEPs). TMS was applied at baseline and at four time points (0, 30, 60, and 180 min) after training. For EEG, task-related power and coherence were calculated for early and late training phases. The conditioned MEP was facilitated at a 2-ms conditioning-test interval before training. However, facilitation was abolished immediately following training, but returned to baseline at subsequent time points. Regional EEG activity and interregional connectivity between PPC and M1 showed an initial increase during early training followed by a significant decrease in the late phases. The findings indicate that parietal–motor interactions are activated during early sensorimotor training when sensory information has to be integrated into a coherent movement plan. Once the sequence is encoded and movements become automatized, PPC–M1 connectivity returns to baseline. PMID:22442568

  18. Presence and Absence of Muscle Contraction Elicited by Peripheral Nerve Electrical Stimulation Differentially Modulate Primary Motor Cortex Excitability

    PubMed Central

    Sasaki, Ryoki; Kotan, Shinichi; Nakagawa, Masaki; Miyaguchi, Shota; Kojima, Sho; Saito, Kei; Inukai, Yasuto; Onishi, Hideaki

    2017-01-01

    Modulation of cortical excitability by sensory inputs is a critical component of sensorimotor integration. Sensory afferents, including muscle and joint afferents, to somatosensory cortex (S1) modulate primary motor cortex (M1) excitability, but the effects of muscle and joint afferents specifically activated by muscle contraction are unknown. We compared motor evoked potentials (MEPs) following median nerve stimulation (MNS) above and below the contraction threshold based on the persistence of M-waves. Peripheral nerve electrical stimulation (PES) conditions, including right MNS at the wrist at 110% motor threshold (MT; 110% MNS condition), right MNS at the index finger (sensory digit nerve stimulation [DNS]) with stimulus intensity approximately 110% MNS (DNS condition), and right MNS at the wrist at 90% MT (90% MNS condition) were applied. PES was administered in a 4 s ON and 6 s OFF cycle for 20 min at 30 Hz. In Experiment 1 (n = 15), MEPs were recorded from the right abductor pollicis brevis (APB) before (baseline) and after PES. In Experiment 2 (n = 15), M- and F-waves were recorded from the right APB. Stimulation at 110% MNS at the wrist evoking muscle contraction increased MEP amplitudes after PES compared with those at baseline, whereas DNS at the index finger and 90% MNS at the wrist not evoking muscle contraction decreased MEP amplitudes after PES. M- and F-waves, which reflect spinal cord or muscular and neuromuscular junctions, did not change following PES. These results suggest that muscle contraction and concomitant muscle/joint afferent inputs specifically enhance M1 excitability. PMID:28392766

  19. BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome.

    PubMed

    Marsili, L; Suppa, A; Di Stasio, F; Belvisi, D; Upadhyay, N; Berardelli, I; Pasquini, M; Petrucci, S; Ginevrino, M; Fabbrini, G; Cardona, F; Defazio, G; Berardelli, A

    2017-03-01

    Gilles de la Tourette syndrome (GTS) is characterized by motor and vocal tics and often associated with obsessive-compulsive disorder (OCD). Responses to intermittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF polymorphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex-matched healthy subjects. In GTS patients, motor and psychiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS according to BDNF polymorphism (Val/Val vs Met carriers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carriers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met ca