Sample records for abnormal spontaneous activity

  1. Tinnitus Perception and Distress Is Related to Abnormal Spontaneous Brain Activity as Measured by Magnetoencephalography

    PubMed Central

    Weisz, Nathan; Moratti, Stephan; Meinzer, Marcus; Dohrmann, Katalin; Elbert, Thomas

    2005-01-01

    Background The neurophysiological mechanisms underlying tinnitus perception are not well understood. Surprisingly, there have been no group studies comparing abnormalities in ongoing, spontaneous neuronal activity in individuals with and without tinnitus perception. Methods and Findings Here, we show that the spontaneous neuronal activity of a group of individuals with tinnitus (n = 17) is characterised by a marked reduction in alpha (8–12 Hz) power together with an enhancement in delta (1.5–4 Hz) as compared to a normal hearing control group (n = 16). This pattern was especially pronounced for temporal regions. Moreover, correlations with tinnitus-related distress revealed strong associations with this abnormal spontaneous activity pattern, particularly in right temporal and left frontal areas. Overall, effects were stronger for the alpha than for the delta frequency band. A data stream of 5 min, recorded with a whole-head neuromagnetometer under a resting condition, was sufficient to extract the marked differences. Conclusions Despite some limitations, there are arguments that the regional pattern of abnormal spontaneous activity we found could reflect a tinnitus-related cortical network. This finding, which suggests that a neurofeedback approach could reduce the adverse effects of this disturbing condition, could have important implications for the treatment of tinnitus. PMID:15971936

  2. Abnormal Spontaneous Brain Activity in Patients With Anisometropic Amblyopia Using Resting-State Functional Magnetic Resonance Imaging.

    PubMed

    Tang, Angcang; Chen, Taolin; Zhang, Junran; Gong, Qiyong; Liu, Longqian

    2017-09-01

    To explore the abnormality of spontaneous activity in patients with anisometropic amblyopia under resting-state functional magnetic resonance imaging (Rs-fMRI). Twenty-four participants were split into two groups. The anisometropic amblyopia group had 10 patients, all of whom had anisometropic amblyopia of the right eye, and the control group had 14 healthy subjects. All participants underwent Rs-fMRI scanning. Measurement of amplitude of low frequency fluctuations of the brain, which is a measure of the amplitudes of spontaneous brain activity, was used to investigate brain changes between the anisometropic amblyopia and control groups. Compared with an age- and gender-matched control group, the anisometropic amblyopia group showed increased amplitude of low frequency fluctuations of spontaneous brain activity in the left superior temporal gyrus, the left inferior parietal lobe, the left pons, and the right inferior semi-lunar lobe. The anisometropic amblyopia group also showed decreased amplitude of low frequency fluctuations in the bilateral medial frontal gyrus. This study demonstrated abnormal spontaneous brain activities in patients with anisometropic amblyopia under Rs-fMRI, and these abnormalities might contribute to the neuropathological mechanisms of anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(5):303-310.]. Copyright 2017, SLACK Incorporated.

  3. Abnormal spontaneous brain activity is associated with impaired emotion and cognition in hyperthyroidism: A rs-fMRI study.

    PubMed

    Zhi, Mengmeng; Hou, Zhenghua; We, Qiong; Zhang, Yuqun; Li, Ling; Yuan, Yonggui

    2018-06-07

    Hyperthyroid patients undergo emotional and cognitive dysfunction. However, the neurological basis for it remains ambiguous. Amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) were used to investigate abnormal spontaneous activity in hyperthyroidism for the first time. 29 hyperthyroid patients and 29 healthy controls (HC) received 3.0T magnetic resonance imaging (MRI) scans and neuropsychological assessments. Compared with HC, hyperthyroid patients showed decreased ALFF in left medial frontal gyrus (MeFG) and left posterior cingulate cortex (PCC). Hyperthyroidism group exhibited decreased ReHo in left MeFG. Within hyperthyroidism group, ALFF values in left MeFG were positively correlated with Hamilton Anxiety Rating Scale (HARS) Z-scores, but negatively correlated with processing speed Z-scores. Besides, ALFF values in left precuneus had a positive correlation with HARS Z-scores. As a result, abnormal brain spontaneous activity mainly in default mode network (DMN) implicated the neuro-pathological substrate of relevant emotional and cognitive dysfunction in hyperthyroid patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Etiology of spontaneous abortion before and after the demonstration of embryonic cardiac activity in women with recurrent spontaneous abortion.

    PubMed

    Liu, Yukun; Liu, Yinglin; Zhang, Shuning; Chen, Hui; Liu, Meilan; Zhang, Jianping

    2015-05-01

    To analyze the etiologic factors of spontaneous abortion in the first trimester among women with recurrent spontaneous abortion, specifically before and after the demonstration of embryonic cardiac activity. A retrospective analysis included women with recurrent spontaneous abortion admitted to a center in Guangzhou, China, for dilation and curettage after a spontaneous abortion in the first trimester between January 2008 and December 2012. The etiologic factors of spontaneous abortion occurring before versus after the demonstration of cardiac activity were compared. A total of 232 women were included. Among 146 women with demonstrated cardiac activity before spontaneous abortion, 78 (53.4%) had an embryonic karyotype abnormality, 55 (37.7%) had traditional etiologic factors, and 34 (23.3%) had an unidentified cause. Among 86 women without cardiac activity, 41 (47.7%) had an embryonic karyotype abnormality, 28 (32.6%) had traditional etiologic factors, and 26 (30.2%) had an unidentified cause. After exclusion of abortions involving embryonic karyotype abnormalities, there was a higher incidence of APA positivity in the group with embryonic cardiac activity than in the other group (13/68 [19.1%] vs 1/45 [2.2%]; P=0.008) and a lower incidence of subclinical hypothyroidism (8/68 [11.8%] vs 12/45 [26.7%]; P=0.042). The distribution of etiologic factors in spontaneous abortion differs according to whether embryonic cardiac activity is recorded. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  5. [Relationship of abnormal sperm DNA methylation with early spontaneous abortion].

    PubMed

    Pan, Lian-Jun; Ma, Jie-Hua; Zhang, Feng-Lei; Zhao, Dan; Pan, Feng; Zhang, Xing-Yuan

    2016-10-01

    To investigate the relationship between the abnormal sperm DNA methylation level and early spontaneous abortion. We randomly selected 98 males who met the inclusion criteria and whose wives suffered from unexplained abortion or embryo abortion, and included another 46 normal healthy men present for pre-pregnancy check-up as controls. We examined the semen quality and sperm morphology, obtained the sperm DNA fragmentation index (DFI) by modified sperm chromatin dispersion, and measured the sperm DNA methylation level using the methylated DNA quantification kit and the colorimetric method. Compared with the normal controls, the men in the unexplained abortion group showed a significantly lower rate of big-halo sperm ([45.50 ± 26.27] vs [36.49 ± 23.06]%, P = 0.038), a higher rate of abnormal-head sperm ([77.08± 12.21] vs [81.09± 10.89]%, P = 0.049), and a lower level of sperm DNA methylation ([0.47 ± 0.33] vs [0.36 ± 0.26] ng/μl, P = 0.035). The sperm DNA methylation level was positively correlated with the percentage of big-halo sperm (OR=0.546, P<0.01). Multivariate regression analysis manifested that sperm head abnormality was an independent risk factor of early spontaneous abortion or embryo abortion (OR=1.032, P = 0.049), while the high methylation level was protective factor against early spontaneous abortion or embryo abortion (OR=0.244, P = 0.03). The abnormal level of sperm DNA methylation may be one of the important reasons for early spontaneous abortion or embryo abortion.

  6. Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

    PubMed

    Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

    2013-04-01

    We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

  7. Which nerve conduction parameters can predict spontaneous electromyographic activity in carpal tunnel syndrome?

    PubMed

    Chang, Chia-Wei; Lee, Wei-Ju; Liao, Yi-Chu; Chang, Ming-Hong

    2013-11-01

    We investigate electrodiagnostic markers to determine which parameters are the best predictors of spontaneous electromyographic (EMG) activity in carpal tunnel syndrome (CTS). We enrolled 229 patients with clinically proven and nerve conduction study (NCS)-proven CTS, as well as 100 normal control subjects. All subjects were evaluated using electrodiagnostic techniques, including median distal sensory latencies (DSLs), sensory nerve action potentials (SNAPs), distal motor latencies (DMLs), compound muscle action potentials (CMAPs), forearm median nerve conduction velocities (FMCVs) and wrist-palm motor conduction velocities (W-P MCVs). All CTS patients underwent EMG examination of the abductor pollicis brevis (APB) muscle, and the presence or absence of spontaneous EMG activities was recorded. Normal limits were determined by calculating the means ± 2 standard deviations from the control data. Associations between parameters from the NCS and EMG findings were investigated. In patients with clinically diagnosed CTS, abnormal median CMAP amplitudes were the best predictors of spontaneous activity during EMG examination (p<0.001; OR 36.58; 95% CI 15.85-84.43). If the median CMAP amplitude was ≤ 2.1 mV, the rate of occurrence of spontaneous EMG activity was >95% (positive predictive rate >95%). If the median CMAP amplitude was higher than the normal limit (>4.9 mV), the rate of no spontaneous EMG activity was >94% (negative predictive rate >94%). An abnormal SNAP amplitude was the second best predictor of spontaneous EMG activity (p<0.001; OR 4.13; 95% CI 2.16-7.90), and an abnormal FMCV was the third best predictor (p=0.01; OR 2.10; 95% CI 1.20-3.67). No other nerve conduction parameters had significant power to predict spontaneous activity upon EMG examination. The CMAP amplitudes of the APB are the most powerful predictors of the occurrence of spontaneous EMG activity. Low CMAP amplitudes are strongly associated with spontaneous activity, whereas high CMAP

  8. Neurofeedback Tunes Scale-Free Dynamics in Spontaneous Brain Activity.

    PubMed

    Ros, T; Frewen, P; Théberge, J; Michela, A; Kluetsch, R; Mueller, A; Candrian, G; Jetly, R; Vuilleumier, P; Lanius, R A

    2017-10-01

    Brain oscillations exhibit long-range temporal correlations (LRTCs), which reflect the regularity of their fluctuations: low values representing more random (decorrelated) while high values more persistent (correlated) dynamics. LRTCs constitute supporting evidence that the brain operates near criticality, a state where neuronal activities are balanced between order and randomness. Here, healthy adults used closed-loop brain training (neurofeedback, NFB) to reduce the amplitude of alpha oscillations, producing a significant increase in spontaneous LRTCs post-training. This effect was reproduced in patients with post-traumatic stress disorder, where abnormally random dynamics were reversed by NFB, correlating with significant improvements in hyperarousal. Notably, regions manifesting abnormally low LRTCs (i.e., excessive randomness) normalized toward healthy population levels, consistent with theoretical predictions about self-organized criticality. Hence, when exposed to appropriate training, spontaneous cortical activity reveals a residual capacity for "self-tuning" its own temporal complexity, despite manifesting the abnormal dynamics seen in individuals with psychiatric disorder. Lastly, we observed an inverse-U relationship between strength of LRTC and oscillation amplitude, suggesting a breakdown of long-range dependence at high/low synchronization extremes, in line with recent computational models. Together, our findings offer a broader mechanistic framework for motivating research and clinical applications of NFB, encompassing disorders with perturbed LRTCs. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Changes in spontaneous brain activity in early Parkinson's disease.

    PubMed

    Yang, Hong; Zhou, Xiaohong Joe; Zhang, Min-Ming; Zheng, Xu-Ning; Zhao, Yi-Lei; Wang, Jue

    2013-08-09

    Resting state brain activity can provide valuable insights into the pathophysiology of Parkinson's disease (PD). The purpose of the present study was (a) to investigate abnormal spontaneous neuronal activity in early PD patients using resting-state functional MRI (fMRI) with a regional homogeneity (ReHo) method and (b) to demonstrate the potential of using changes in abnormal spontaneous neuronal activity for monitoring the progression of PD during its early stages. Seventeen early PD patients were assessed with the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr disability scale and the Mini-mental State Examination (MMSE) were compared with seventeen gender- and age-matched healthy controls. All subjects underwent MRI scans using a 1.5T General Electric Signa Excite II scanner. The MRI scan protocol included whole-brain volumetric imaging using a 3D inversion recovery prepared (IR-Prep) fast spoiled gradient-echo pulse sequence and 2D multi-slice (22 axial slices covering the whole brain) resting-state fMRI using an echo planar imaging (EPI) sequence. Images were analyzed in SPM5 together with a ReHo algorithm using the in-house software program REST. A corrected threshold of p<0.05 was determined by AlphaSim and used in statistical analysis. Compared with the healthy controls, the early PD group showed significantly increased ReHo in a number of brain regions, including the left cerebellum, left parietal lobe, right middle temporal lobe, right sub-thalamic nucleus areas, right superior frontal gyrus, middle frontal gyrus (MFG), right inferior parietal lobe (IPL), right precuneus lobe, left MFG and left IPL. Additionally, significantly reduced ReHo was also observed in the early PD patients in the following brain regions: the left putamen, left inferior frontal gyrus, right hippocampus, right anterior cingulum, and bilateral lingual gyrus. Moreover, in PD patients, ReHo in the left putamen was negatively correlated with the UPDRS scores (r=-0

  10. Spontaneous Gamma Activity in Schizophrenia.

    PubMed

    Hirano, Yoji; Oribe, Naoya; Kanba, Shigenobu; Onitsuka, Toshiaki; Nestor, Paul G; Spencer, Kevin M

    2015-08-01

    A major goal of translational neuroscience is to identify neural circuit abnormalities in neuropsychiatric disorders that can be studied in animal models to facilitate the development of new treatments. Oscillations in the gamma band (30-100 Hz) of the electroencephalogram have received considerable interest as the basic mechanisms underlying these oscillations are understood, and gamma abnormalities have been found in schizophrenia (SZ). Animal models of SZ based on hypofunction of the N-methyl-d-aspartate receptor (NMDAR) demonstrate increased spontaneous broadband gamma power, but this phenomenon has not been identified clearly in patients with SZ. To examine spontaneous gamma power and its relationship to evoked gamma oscillations in the auditory cortex of patients with SZ. We performed a cross-sectional study including 24 patients with chronic SZ and 24 matched healthy control participants at the Veterans Affairs Boston Healthcare System from January 1, 2009, through December 31, 2012. Electroencephalograms were obtained during auditory steady-state stimulation at multiple frequencies (20, 30, and 40 Hz) and during a resting state in 18 participants in each group. Electroencephalographic activity in the auditory cortex was estimated using dipole source localization. Auditory steady-state response (ASSR) measures included the phase-locking factor and evoked power. Spontaneous gamma power was measured as induced (non-phase-locked) gamma power in the ASSR data and as total gamma power in the resting-state data. The ASSR phase-locking factor was reduced significantly in patients with SZ compared with controls for the 40-Hz stimulation (mean [SD], 0.075 [0.028] vs 0.113 [0.065]; F1,46 = 6.79 [P = .012]) but not the 20- or the 30-Hz stimulation (0.042 [0.038] vs 0.043 [0.034]; F1,46 = 0.006 [P = .938] and 0.084 [0.040] vs 0.098 [0.050]; F1,46 = 1.605 [P = .212], respectively), repeating previous findings. The mean [SD] broadband-induced (30

  11. Altered Spontaneous Brain Activity in Betel Quid Dependence

    PubMed Central

    Liu, Tao; Li, Jian-jun; Zhao, Zhong-yan; Yang, Guo-shuai; Pan, Meng-jie; Li, Chang-qing; Pan, Su-yue; Chen, Feng

    2016-01-01

    Abstract It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate. In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate. The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID

  12. Development of a spontaneously active dorsal root ganglia assay using multiwell multielectrode arrays

    PubMed Central

    Newberry, Kim; Wang, Shuya; Hoque, Nina; Kiss, Laszlo; Ahlijanian, Michael K.; Herrington, James

    2016-01-01

    In vitro phenotypic assays of sensory neuron activity are important tools for identifying potential analgesic compounds. These assays are typically characterized by hyperexcitable and/or abnormally, spontaneously active cells. Whereas manual electrophysiology experiments provide high-resolution biophysical data to characterize both in vitro models and potential therapeutic modalities (e.g., action potential characteristics, the role of specific ion channels, and receptors), these techniques are hampered by their low throughput. We have established a spontaneously active dorsal root ganglia (DRG) platform using multiwell multielectrode arrays (MEAs) that greatly increase the ability to evaluate the effects of multiple compounds and conditions on DRG excitability within the context of a cellular network. We show that spontaneous DRG firing can be attenuated with selective Na+ and Ca2+ channel blockers, as well as enhanced with K+ channel blockers. In addition, spontaneous activity can be augmented with both the transient receptor potential cation channel subfamily V member 1 agonist capsaicin and the peptide bradykinin and completely blocked with neurokinin receptor antagonists. Finally, we validated the use of this assay by demonstrating that commonly used neuropathic pain therapeutics suppress DRG spontaneous activity. Overall, we have optimized primary rat DRG cells on a multiwell MEA platform to generate and characterize spontaneously active cultures that have the potential to be used as an in vitro phenotypic assay to evaluate potential therapeutics in rodent models of pain. PMID:27052585

  13. Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.

    PubMed Central

    Grainick, H R; Williams, S B; McKeown, L P; Rick, M E; Maisonneuve, P; Jenneau, C; Sultan, Y

    1985-01-01

    We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes

  14. Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

    PubMed Central

    Nakao, Kazuhito; Nakazawa, Kazu

    2014-01-01

    In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The “paradoxically” high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception. PMID:25018691

  15. Respiration in vitro: I. Spontaneous activity.

    PubMed

    Hamada, O; Garcia-Rill, E; Skinner, R D

    1992-01-01

    The present report describes respiratory-like activity recorded from intercostal muscles in the neonatal rat in vitro brain stem-spinal cord, rib-attached preparation. In this preparation from 1- to 4-day-old rats, spontaneous rhythmic and synchronized upward movements of the rib cage coincided with the recorded muscle activity. Spontaneous respiratory-like activity showed a frequency in the range of 0.05-0.2 Hz, with single-, double-, and mixed-burst patterns. Spontaneous activity declined over time, but increased in frequency as temperature increased. Multilevel recordings showed a cephalocaudal order of bursting of intercostal muscles. Brain stem transections at the prepontine level did not affect spontaneous frequency, whereas premedullary transections resulted in an increase in spontaneous respiratory frequency. High spinal transections eliminated spontaneous respiratory-like activity. These results suggest that there is a well-organized pontomedullary pattern generator for respiratory-like activity in this preparation, which can be modulated by temperature. The characteristics of these electromyographic (EMG) recordings allow comparison with previous in vitro studies of respiratory-like activity using nerve activity and in vivo studies using EMG activity. These results provide basic information on the spontaneous activity of this preparation as a prelude to the study of the effects of electrical stimulation of the spinal cord to induce respiratory-like activity, as described in the companion article.

  16. Altered Spontaneous Activity in Anisometropic Amblyopia Subjects: Revealed by Resting-State fMRI

    PubMed Central

    Lin, Xiaoming; Ding, Kun; Liu, Yong; Yan, Xiaohe; Song, Shaojie; Jiang, Tianzi

    2012-01-01

    Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo), a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia. PMID:22937041

  17. Traditional karyotyping vs copy number variation sequencing for detection of chromosomal abnormalities associated with spontaneous miscarriage.

    PubMed

    Liu, S; Song, L; Cram, D S; Xiong, L; Wang, K; Wu, R; Liu, J; Deng, K; Jia, B; Zhong, M; Yang, F

    2015-10-01

    To compare the performance of traditional G-banding karyotyping with that of copy number variation sequencing (CNV-Seq) for detection of chromosomal abnormalities associated with miscarriage. Products of conception (POC) were collected from spontaneous miscarriages. Chromosomal abnormalities were detected using high-resolution G-banding karyotyping and CNV sequencing. Quantitative fluorescent polymerase chain reaction analysis of maternal and POC DNA for short tandem repeat (STR) markers was used to both monitor maternal cell contamination and confirm the chromosomal status and sex of the miscarriage tissue. A total of 64 samples of POC, comprising 16 with an abnormal and 48 with a normal karyotype, were selected and coded for analysis by CNV-Seq. CNV-Seq results were concordant for 14 (87.5%) of the 16 gross chromosomal abnormalities identified by karyotyping, including 11 autosomal trisomies and three sex chromosomal aneuploidies (45,X). Of the two discordant results, a 69,XXX polyploidy was missed by CNV-Seq, although supporting STR marker analysis confirmed the triploidy. In contrast, CNV-Seq identified a sample with 45,X karyotype as a 45,X/46,XY mosaic. In the remaining 48 samples of POC with a normal karyotype, CNV-Seq detected a 2.58-Mb 22q deletion associated with DiGeorge syndrome and nine different smaller CNVs of no apparent clinical significance. CNV-Seq used in parallel with STR profiling is a reliable and accurate alternative to karyotyping for identifying chromosome copy number abnormalities associated with spontaneous miscarriage. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

  18. Spontaneous network activity and synaptic development

    PubMed Central

    Kerschensteiner, Daniel

    2014-01-01

    Throughout development, the nervous system produces patterned spontaneous activity. Research over the last two decades has revealed a core group of mechanisms that mediate spontaneous activity in diverse circuits. Many circuits engage several of these mechanisms sequentially to accommodate developmental changes in connectivity. In addition to shared mechanisms, activity propagates through developing circuits and neuronal pathways (i.e. linked circuits in different brain areas) in stereotypic patterns. Increasing evidence suggests that spontaneous network activity shapes synaptic development in vivo. Variations in activity-dependent plasticity may explain how similar mechanisms and patterns of activity can be employed to establish diverse circuits. Here, I will review common mechanisms and patterns of spontaneous activity in emerging neural networks and discuss recent insights into their contribution to synaptic development. PMID:24280071

  19. Spontaneous alterations of regional brain activity in patients with adult generalized anxiety disorder

    PubMed Central

    Xia, Likun; Li, Shumei; Wang, Tianyue; Guo, Yaping; Meng, Lihong; Feng, Yunping; Cui, Yu; Wang, Fan; Ma, Jian; Jiang, Guihua

    2017-01-01

    Objective We aimed to examine how spontaneous brain activity might be related to the pathophysiology of generalized anxiety disorder (GAD). Patients and methods Using resting-state functional MRI, we examined spontaneous regional brain activity in 31 GAD patients (mean age, 36.87±9.16 years) and 36 healthy control participants (mean age, 39.53±8.83 years) matched for age, education, and sex from December 2014 to October 2015. We performed a two-sample t-test on the voxel-based analysis of the regional homogeneity (ReHo) maps. We used Pearson correlation analysis to compare scores from the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, State–Trait Anxiety Scale-Trait Scale, and mean ReHo values. Results We found abnormal spontaneous activity in multiple regions of brain in GAD patients, especially in the sensorimotor cortex and emotional regions. GAD patients showed decreased ReHo values in the right orbital middle frontal gyrus, left anterior cingulate cortex, right middle frontal gyrus, and bilateral supplementary motor areas, with increased ReHo values in the left middle temporal gyrus, left superior temporal gyrus, and right superior occipital gyrus. The ReHo value of the left middle temporal gyrus correlated positively with the Hamilton Anxiety Rating Scale scores. Conclusion These results suggest that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of GAD. PMID:28790831

  20. Altered spontaneous brain activity in Cushing's disease: a resting-state functional MRI study.

    PubMed

    Jiang, Hong; He, Na-Ying; Sun, Yu-Hao; Jian, Fang-Fang; Bian, Liu-Guan; Shen, Jian-Kang; Yan, Fu-Hua; Pan, Si-Jian; Sun, Qing-Fang

    2017-03-01

    Cushing's disease (CD) provides a unique and naturalist model for studying the influence of hypercortisolism on the human brain and the reversibility of these effects after resolution of the condition. This cross-sectional study used resting-state fMRI (rs-fMRI) to investigate the altered spontaneous brain activity in CD patients and the trends for potential reversibility after the resolution of the hypercortisolism. We also aim to determine the relationship of these changes with clinical characteristics and cortisol levels. Active CD patients (n = 18), remitted CD patients (n = 14) and healthy control subjects (n = 22) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Our study resulted in three major findings: (i) active CD patients showed significantly altered spontaneous brain activity in the posterior cingulate cortex (PCC)/precuneus (PCu), occipital lobe (OC)/cerebellum, thalamus, right postcentral gyrus (PoCG) and left prefrontal cortex (PFC); (ii) trends for partial restoration of altered spontaneous brain activity after the resolution hypercortisolism were found in several brain regions; and (iii) active CD patients showed a significant correlation between cortisol levels and ALFF/ReHo values in the PCC/PCu, a small cluster in the OC and the right IPL. This study provides a new approach to investigating brain function abnormalities in patients with CD and enhances our understanding of the effect of hypercortisolism on the human brain. Furthermore, our explorative potential reversibility study of patients with CD may facilitate the development of future longitudinal studies. © 2016 John Wiley & Sons Ltd.

  1. Phorbol ester and spontaneous activity in SHR aorta

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moisey, D.M.; Cox, R.H.

    1986-03-01

    Thoracic aortas (TA) were excised from 6-week old SHR and WKY. 2mm rings were mounted isometrically at optimum preload. Spontaneous rhythmical activity developed in TA from SHR and had a frequency of 3-4/min with varying periods of quiescence between bursts of activity. The spontaneous activity often produced an increase in tension development which was associated with increased frequency of oscillations. Verapamil (10/sup -7/ M) or Ca/sup + +/-free solution added during the contractile phase resulted in an immediate loss of tension and spontaneous activity. Addition of ouabain (10/sup -4/ M) during the contractile phase of spontaneous activity, increased the frequencymore » of oscillations which appeared to fuse into a tetanus. Spontaneous rhythmical activity was infrequently observed in TA from WKY. However, addition of phorbol 12-myristate-13 acetate (TPA), frequently induced spontaneous rhythmic oscillations associated with tension development in TA from WKY. TPA contracted the SHR TA and increased the frequency of oscillations. SHR TA were more sensitive to TPA than WKY. This study demonstrates (1) spontaneous rhythmical activity, independent of agonist stimulation in TA from 6-week old SHR and (2) TPA induced spontaneous oscillatory activity. The mechanism underlying the spontaneous oscillatory activity may involve membrane coupling events and Na-pump difference between SHR and WKY.« less

  2. Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings.

    PubMed

    Liu, Chang; Xue, Zhimin; Palaniyappan, Lena; Zhou, Li; Liu, Haihong; Qi, Chang; Wu, Guowei; Mwansisya, Tumbwene E; Tao, Haojuan; Chen, Xudong; Huang, Xiaojun; Liu, Zhening; Pu, Weidan

    2016-03-01

    Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus. This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Altered spontaneous brain activity in patients with hemifacial spasm: a resting-state functional MRI study.

    PubMed

    Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

    2015-01-01

    Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS.

  4. Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

    PubMed

    Wu, Qiong; Zhang, Xiaocui; Dong, Daifeng; Wang, Xiang; Yao, Shuqiao

    2017-07-01

    Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

  5. Abnormal oxygen homeostasis in the nucleus tractus solitarii of the spontaneously hypertensive rat.

    PubMed

    Hosford, Patrick S; Millar, Julian; Ramage, Andrew G; Marina, Nephtali

    2017-04-01

    What is the central question of this study? Arterial hypertension is associated with impaired neurovascular coupling in the somatosensory cortex. Abnormalities in activity-dependent oxygen consumption in brainstem regions involved in the control of cardiovascular reflexes have not been explored previously. What is the main finding and its importance? Using fast-cyclic voltammetry, we found that changes in local tissue PO2 in the nucleus tractus solitarii induced by electrical stimulation of the vagus nerve are significantly impaired in spontaneously hypertensive rats. This is consistent with previous observations showing that brainstem hypoxia plays an important role in the pathogenesis of arterial hypertension. The effects of arterial hypertension on cerebral blood flow remain poorly understood. Haemodynamic responses within the somatosensory cortex have been shown to be impaired in the spontaneously hypertensive rat (SHR) model. However, it is unknown whether arterial hypertension affects oxygen homeostasis in vital brainstem areas that control cardiovascular reflexes. In this study, we assessed vagus nerve stimulation-induced changes in local tissue PO2 (PtO2) in the caudal nucleus tractus solitarii (cNTS) of SHRs and normotensive Wistar rats. Measurements of PtO2 were performed using a novel application of fast-cyclic voltammetry, which allows higher temporal resolution of O 2 changes than traditional optical fluorescence techniques. Electrical stimulation of the central cut end of the vagus nerve (ESVN) caused profound reductions in arterial blood pressure along with biphasic changes in PtO2 in the cNTS, characterized by a rapid decrease in PtO2 ('initial dip') followed by a post-stimulus overshoot above baseline. The initial dip was found to be significantly smaller in SHRs compared with normotensive Wistar rats even after ganglionic blockade. The post-ESVN overshoot was similar in both groups but was reduced in Wistar rats after ganglionic blockade. In

  6. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

    PubMed

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.

  7. Increased pCREB expression and the spontaneous epileptiform activity in a BCNU-treated rat model of cortical dysplasia.

    PubMed

    Pennacchio, Paolo; Noé, Francesco; Gnatkovsky, Vadym; Moroni, Ramona Frida; Zucca, Ileana; Regondi, Maria Cristina; Inverardi, Francesca; de Curtis, Marco; Frassoni, Carolina

    2015-09-01

    Cortical dysplasias (CDs) represent a wide range of cortical abnormalities that closely correlate with intractable epilepsy. Rats prenatally exposed to 1-3-bis-chloroethyl-nitrosurea (BCNU) represent an injury-based model that reproduces many histopathologic features of human CD. Previous studies reported in vivo hyperexcitability in this model, but in vivo epileptogenicity has not been confirmed. To determine whether cortical and hippocampal lesions lead to epileptiform discharges and/or seizures in the BCNU model, rats at three different ages (3, 5, and 9 months old) were implanted for long-term video electroencephalographic recording. At the end of the recording session, brain tissue was processed for histologic and immunohistochemical investigation including cAMP response element binding protein (CREB) phosphorylation, as a biomarker of epileptogenicity. BCNU-treated rats showed spontaneous epileptiform activity (67%) in the absence of a second seizure-provoking hit. Such activity originated mainly from one hippocampus and propagated to the ipsilateral neocortex. No epileptiform activity was found in age-matched control rats. The histopathologic investigation revealed that all BCNU rats with epileptiform activity showed neocortical and hippocampal abnormalities; the presence and the severity of these lesions did not correlate consistently with the propensity to generate epileptiform discharges. Epileptiform activity was found only in cortical areas of BCNU-treated rats in which a correlation between brain abnormalities and increased pCREB expression was observed. This study demonstrates the in vivo occurrence of spontaneous epileptiform discharges in the BCNU model and shows that increased pCREB expression can be utilized as a reliable biomarker of epileptogenicity. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  8. Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I.

    PubMed

    Walton, K D; Dubois, M; Llinás, R R

    2010-07-01

    Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. The study addresses spontaneous MEG activity from 13 awake, adult patients (2 men, 11 women; age 15-62), with CRPS Type I of one extremity (duration range: 3months to 10years) and from 13 control subjects. All CRPS I patients demonstrated peaks in power spectrum in the delta (<4Hz) and/or theta (4-9Hz) frequency ranges resulting in a characteristically increased spectral power in those ranges when compared to control subjects. The localization of such abnormal activity, implemented using independent component analysis (ICA) of the sensor data, showed delta and/or theta range activity localized to the somatosensory cortex corresponding to the pain localization, and to orbitofrontal-temporal cortices related to the affective pain perception. Indeed, CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  9. Associative memory model with spontaneous neural activity

    NASA Astrophysics Data System (ADS)

    Kurikawa, Tomoki; Kaneko, Kunihiko

    2012-05-01

    We propose a novel associative memory model wherein the neural activity without an input (i.e., spontaneous activity) is modified by an input to generate a target response that is memorized for recall upon the same input. Suitable design of synaptic connections enables the model to memorize input/output (I/O) mappings equaling 70% of the total number of neurons, where the evoked activity distinguishes a target pattern from others. Spontaneous neural activity without an input shows chaotic dynamics but keeps some similarity with evoked activities, as reported in recent experimental studies.

  10. Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

    PubMed

    Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

    2016-11-01

    The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

  11. Benefit of azilsartan on blood pressure elevation around rest-to-active phase in spontaneously hypertensive rats.

    PubMed

    Isegawa, Kengo; Hirooka, Yoshitaka; Kishi, Takuya; Yasukawa, Keiji; Utsumi, Hideo; Sunagawa, Kenji

    2015-01-01

    Abnormal elevation of blood pressure in early morning (rest-to-active phase) is suggested to cause cardiovascular events. We investigated whether azilsartan (AZL), a novel potent angiotensin receptor blocker, suppresses blood pressure elevation from the light-rest to dark-active phase in spontaneously hypertensive rats (SHRs). AZL has a sustained depressor effect around the rest-to-active phase in SHRs to a greater extent than candesartan (CAN), despite their similar depressor effects for over 24 h. AZL did not cause sympathoexcitation. These results suggest that AZL has a more sustained depressor effect than CAN around the rest-to-active phase in SHRs, and might have advantages for early morning hypertension.

  12. Knockdown of sodium channel NaV1.6 blocks mechanical pain and abnormal bursting activity of afferent neurons in inflamed sensory ganglia

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Ye, Ling; Mao, Ju-Xian; Zhang, Jun-Ming

    2013-01-01

    Inflammatory processes in the sensory ganglia contribute to many forms of chronic pain. We previously showed that local inflammation of the lumbar sensory ganglia rapidly leads to prolonged mechanical pain behaviors and high levels of spontaneous bursting activity in myelinated cells. Abnormal spontaneous activity of sensory neurons occurs early in many preclinical pain models, and initiates many other pathological changes, but its molecular basis is not well understood. The sodium channel isoform NaV1.6 can underlie repetitive firing and excitatory persistent and resurgent currents. We used in vivo knockdown of this channel via local injection of siRNA to examine its role in chronic pain following local inflammation of the rat lumbar sensory ganglia. In normal DRG, quantitative PCR showed that cells capable of firing repetitively had significantly higher relative expression of NaV1.6. In inflamed DRG, spontaneously active bursting cells expressed high levels of NaV1.6′ immunoreactivity. In vivo knockdown of NaV1.6 locally in the lumbar DRG at the time of DRG inflammation completely blocked development of pain behaviors and abnormal spontaneous activity, while having only minor effects on unmyelinated C-cells. Current research on isoform-specific sodium channel blockers for chronic pain is largely focused on NaV1.8, because it is present primarily in unmyelinated C fiber nociceptors, or on NaV1.7, because lack of this channel causes congenital indifference to pain. However, the results suggest that NaV1.6 may be a useful therapeutic target for chronic pain, and that some pain conditions may be primarily mediated by myelinated A-fiber sensory neurons. PMID:23622763

  13. Vision Drives Correlated Activity without Patterned Spontaneous Activity in Developing Xenopus Retina

    PubMed Central

    Demas, James A.; Payne, Hannah; Cline, Hollis T.

    2011-01-01

    Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABAA receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement. PMID:21312343

  14. Spontaneous Activity Drives Local Synaptic Plasticity In Vivo.

    PubMed

    Winnubst, Johan; Cheyne, Juliette E; Niculescu, Dragos; Lohmann, Christian

    2015-07-15

    Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 μm) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. New Perspectives on Spontaneous Brain Activity: Dynamic Networks and Energy Matter.

    PubMed

    Tozzi, Arturo; Zare, Marzieh; Benasich, April A

    2016-01-01

    Spontaneous brain activity has received increasing attention as demonstrated by the exponential rise in the number of published article on this topic over the last 30 years. Such "intrinsic" brain activity, generated in the absence of an explicit task, is frequently associated with resting-state or default-mode networks (DMN)s. The focus on characterizing spontaneous brain activity promises to shed new light on questions concerning the structural and functional architecture of the brain and how they are related to "mind". However, many critical questions have yet to be addressed. In this review, we focus on a scarcely explored area, specifically the energetic requirements and constraints of spontaneous activity, taking into account both thermodynamical and informational perspectives. We argue that the "classical" definitions of spontaneous activity do not take into account an important feature, that is, the critical thermodynamic energetic differences between spontaneous and evoked brain activity. Spontaneous brain activity is associated with slower oscillations compared with evoked, task-related activity, hence it exhibits lower levels of enthalpy and "free-energy" (i.e., the energy that can be converted to do work), thus supporting noteworthy thermodynamic energetic differences between spontaneous and evoked brain activity. Increased spike frequency during evoked activity has a significant metabolic cost, consequently, brain functions traditionally associated with spontaneous activity, such as mind wandering, require less energy that other nervous activities. We also review recent empirical observations in neuroscience, in order to capture how spontaneous brain dynamics and mental function can be embedded in a non-linear dynamical framework, which considers nervous activity in terms of phase spaces, particle trajectories, random walks, attractors and/or paths at the edge of the chaos. This takes us from the thermodynamic free-energy, to the realm of "variational

  16. Spontaneous olfactory receptor neuron activity determines follower cell response properties

    PubMed Central

    Joseph, Joby; Dunn, Felice A.; Stopfer, Mark

    2012-01-01

    Noisy or spontaneous activity is common in neural systems and poses a challenge to detecting and discriminating signals. Here we use the locust to answer fundamental questions about noise in the olfactory system: Where does spontaneous activity originate? How is this activity propagated or reduced throughout multiple stages of neural processing? What mechanisms favor the detection of signals despite the presence of spontaneous activity? We found that spontaneous activity long observed in the secondary projection neurons (PNs) originates almost entirely from the primary olfactory receptor neurons (ORNs) rather than from spontaneous circuit interactions in the antennal lobe, and that spontaneous activity in ORNs tonically depolarizes the resting membrane potentials of their target PNs and local neurons (LNs), and indirectly tonically depolarizes tertiary Kenyon cells (KCs). However, because these neurons have different response thresholds, in the absence of odor stimulation, ORNs and PNs display a high spontaneous firing rate but KCs are nearly silent. Finally, we used a simulation of the olfactory network to show that discrimination of signal and noise in the KCs is best when threshold levels are set so that baseline activity in PNs persists. Our results show how the olfactory system benefits from making a signal detection decision after a point of maximal information convergence, e.g., after KCs pool inputs from many PNs. PMID:22357872

  17. Altered Spontaneous Brain Activity in Betel Quid Dependence: A Resting-state Functional Magnetic Resonance Imaging Study.

    PubMed

    Liu, Tao; Li, Jian-Jun; Zhao, Zhong-Yan; Yang, Guo-Shuai; Pan, Meng-Jie; Li, Chang-Qing; Pan, Su-Yue; Chen, Feng

    2016-02-01

    It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration.Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate.In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate.The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals.

  18. The influence of spontaneous activity on stimulus processing in primary visual cortex.

    PubMed

    Schölvinck, M L; Friston, K J; Rees, G

    2012-02-01

    Spontaneous activity in the resting human brain has been studied extensively; however, how such activity affects the local processing of a sensory stimulus is relatively unknown. Here, we examined the impact of spontaneous activity in primary visual cortex on neuronal and behavioural responses to a simple visual stimulus, using functional MRI. Stimulus-evoked responses remained essentially unchanged by spontaneous fluctuations, combining with them in a largely linear fashion (i.e., with little evidence for an interaction). However, interactions between spontaneous fluctuations and stimulus-evoked responses were evident behaviourally; high levels of spontaneous activity tended to be associated with increased stimulus detection at perceptual threshold. Our results extend those found in studies of spontaneous fluctuations in motor cortex and higher order visual areas, and suggest a fundamental role for spontaneous activity in stimulus processing. Copyright © 2011. Published by Elsevier Inc.

  19. Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

    PubMed

    Yuan, Kai; Jin, Chenwang; Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

    2013-01-01

    The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

  20. Research on spontaneous activity in adult anisometropic amblyopia with regional homogeneity

    NASA Astrophysics Data System (ADS)

    Huang, Yufeng; Zhou, Yifeng

    2017-06-01

    Amblyopia usually occurs in early childhood and results in monocular visual impairment. The functional magnetic resonance imaging (fMRI) studies have reflected functional anomaly in amblyopia. In resting-state fMRI study, spontaneous activity changes abnormally in anisometropic amblyopia could be revealed by the regional homogeneity (ReHo). Twenty two adult anisometropic amblyopes and Twenty one normal controls participated in this fMRI study. Two sample T test was carried out to analysis ReHo within the whole brain for the inter groups. Compare with normal group, our study found that the amblyopia’s ReHo mainly increased in the left frontal lobe, while decreased in the left cerebellum, the temporal lobe (left and right), and the left parietal lobe. And the ReHo values in middle and inferior temporal lobe, the prefrontal lobe, frontal lobe (positive) and parietal lobe and medial frontal gyrus (negative) could be correlated with the acuity deficit of amblyopia. The results increased in ReHo may indicate compensatory plasticity in higher vision information process, while the decreased in ReHo may reflect decreased ability in eye movement, spatial sense and visuo-motor coordination. The correlation revealed that the vision deficit may correspond to the spontaneous in certain brain area.

  1. Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity.

    PubMed

    Speer, Colenso M; Sun, Chao; Liets, Lauren C; Stafford, Ben K; Chapman, Barbara; Cheng, Hwai-Jong

    2014-11-07

    Spontaneous retinal activity (SRA) is important during eye-specific segregation within the dorsal lateral geniculate nucleus (dLGN), but the feature(s) of activity critical for retinogeniculate refinement are controversial. Pharmacologically or genetically manipulating cholinergic signaling during SRA perturbs correlated retinal ganglion cell (RGC) spiking and disrupts eye-specific retinofugal refinement in vivo, consistent with an instructive role for SRA during visual system development. Paradoxically, ablating the starburst amacrine cells (SACs) that generate cholinergic spontaneous activity disrupts correlated RGC firing without impacting retinal activity levels or eye-specific segregation in the dLGN. Such experiments suggest that patterned SRA during retinal waves is not critical for eye-specific refinement and instead, normal activity levels are permissive for retinogeniculate development. Here we revisit the effects of ablating the cholinergic network during eye-specific segregation and show that SAC ablation disrupts, but does not eliminate, retinal waves with no concomitant impact on normal eye-specific segregation in the dLGN. We induced SAC ablation in postnatal ferret pups beginning at birth by intraocular injection of a novel immunotoxin selective for the ferret vesicular acetylcholine transporter (Ferret VAChT-Sap). Through dual-patch whole-cell and multi-electrode array recording we found that SAC ablation altered SRA patterns and led to significantly smaller retinal waves compared with controls. Despite these defects, eye-specific segregation was normal. Further, interocular competition for target territory in the dLGN proceeded in cases where SAC ablation was asymmetric in the two eyes. Our data demonstrate normal eye-specific retinogeniculate development despite significant abnormalities in patterned SRA. Comparing our current results with earlier studies suggests that defects in retinal wave size, absolute levels of SRA, correlations between RGC

  2. Spontaneous beating and synchronization of extensile active filament

    NASA Astrophysics Data System (ADS)

    Sarkar, Debarati; Thakur, Snigdha

    2017-04-01

    We simulate a semi-flexible active filament that exhibits spontaneous oscillations on clamping and show self-propulsion when left free. The activity on the filament relies on the nano-dimers distributed at regular intervals along the chain. With an emphasis on the spontaneous beating of a clamped filament, we demonstrate that the two competing forces necessary for oscillation are the elastic forces due to polymer rigidity and the active forces due to chemical activity. In addition, we also study the synchronization of two extensile filaments and the role played by non-local hydrodynamic interactions. We observe a phase lock scenario between the filaments during their synchronous motion.

  3. Attentional bias modification (ABM) training induces spontaneous brain activity changes in young women with subthreshold depression: a randomized controlled trial.

    PubMed

    Li, H; Wei, D; Browning, M; Du, X; Zhang, Q; Qiu, J

    2016-04-01

    Attention bias modification (ABM) training has been suggested to effectively reduce depressive symptoms, and may be useful in the prevention of the illness in individuals with subthreshold symptoms, yet little is known about the spontaneous brain activity changes associated with ABM training. Resting-state functional MRI was used to explore the effects of ABM training on subthreshold depression (SubD) and corresponding spontaneous brain activity changes. Participants were 41 young women with SubD and 26 matched non-depressed controls. Participants with SubD were randomized to receive either ABM or placebo training during 28 sessions across 4 weeks. Non-depressed controls were assessed before training only. Attentional bias, depressive severity, and spontaneous brain activity before and after training were assessed in both training groups. Findings revealed that compared to active control training, ABM training significantly decreased depression symptoms, and increased attention for positive stimuli. Resting-state data found that ABM training significantly reduced amplitude of low-frequency fluctuations (ALFF) of the right anterior insula (AI) and right middle frontal gyrus which showed greater ALFF than non-depressed controls before training; Functional connectivity strength between right AI and the right frontoinsular and right supramarginal gyrus were significantly decreased after training within the ABM group; moreover, the improvement of depression symptoms following ABM significantly correlated with the connectivity strength reductions between right AI and right frontoinsular and right supramarginal gyrus. These results suggest that ABM has the potential to reshape the abnormal patterns of spontaneous brain activity in relevant neural circuits associated with depression.

  4. Mechanisms of morphine enhancement of spontaneous seizure activity.

    PubMed

    Saboory, Ehsan; Derchansky, Miron; Ismaili, Mohammed; Jahromi, Shokrollah S; Brull, Richard; Carlen, Peter L; El Beheiry, Hossam

    2007-12-01

    High-dose opioid therapy can precipitate seizures; however, the mechanism of such a dangerous adverse effect remains poorly understood. The aim of our study was to determine whether the neuroexcitatory activity of high-dose morphine is mediated by selective stimulation of opioid receptors. Mice hippocampi were resected intact and bathed in low magnesium artificial cerebrospinal fluid to induce spontaneous seizure-like events recorded from CA1 neurons. Application of morphine had a biphasic effect on the recorded spontaneous seizure-like events. In a low concentration (10 microM), morphine depressed electrographic seizure activity. Higher morphine concentrations (30 and 100 microM) enhanced seizure activity in an apparent dose-dependent manner. Naloxone, a nonselective opiate antagonist blocked the proconvulsant action of morphine. Selective mu and kappa opiate receptor agonists and antagonists enhanced and suppressed the spontaneous seizure activity, respectively. On the contrary, delta opioid receptor ligands did not have an effect. The proseizure effect of morphine is mediated through selective stimulation of mu and kappa opiate receptors but not the activation of the delta receptor system. The observed dose-dependent mechanism of morphine neuroexcitation underscores careful adjustment and individualized opioid dosing in the clinical setting.

  5. Reflex effects on renal nerve activity characteristics in spontaneously hypertensive rats.

    PubMed

    DiBona, G F; Jones, S Y; Sawin, L L

    1997-11-01

    The effects of arterial and cardiac baroreflex activation on the discharge characteristics of renal sympathetic nerve activity were evaluated in conscious spontaneously hypertensive and Wistar-Kyoto rats. In spontaneously hypertensive rats compared with Wistar-Kyoto rats, (1) arterial baroreflex regulation of renal sympathetic nerve activity was reset to a higher arterial pressure and the gain was decreased and (2) cardiac baroreflex regulation of renal sympathetic nerve activity exhibited a lower gain. With the use of sympathetic peak detection analysis, the inhibition of integrated renal sympathetic nerve activity, which occurred during both increased arterial pressure (arterial baroreflex) and right atrial pressure (cardiac baroreflex), was due to parallel decreases in peak height with little change in peak frequency in both spontaneously hypertensive and Wistar-Kyoto rats. Arterial and cardiac baroreflex inhibition of renal sympathetic nerve activity in Wistar-Kyoto and spontaneously hypertensive rats is due to a parallel reduction in the number of active renal sympathetic nerve fibers.

  6. On the Dynamics of the Spontaneous Activity in Neuronal Networks

    PubMed Central

    Bonifazi, Paolo; Ruaro, Maria Elisabetta; Torre, Vincent

    2007-01-01

    Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABAA receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics. PMID:17502919

  7. Salicylate-induced abnormal activity in the inferior colliculus of rats.

    PubMed

    Chen, G D; Jastreboff, P J

    1995-02-01

    The evaluation of the spontaneous activity of 471 units from the external nucleus of the IC revealed that salicylate induces an increase of the spontaneous activity and the emergence of a bursting type of activity longer than 4 spikes. For sharply tuned units, the affected cells were from the frequency range of 10-16 kHz, which corresponds to the behaviorally measured pitch of salicylate-induced tinnitus in rats. An exogenous calcium supplement, provided under the conditions shown to attenuate the behavioral manifestation of salicylate-induced tinnitus, abolished the modification of the spontaneous activity induced by salicylate. Finally, profound changes of activity were observed for cells not responding to contralateral sound. We propose that the observed long bursts of discharges represent tinnitus-related neuronal activity. The results are consistent with the hypothesis that GABA-mediated disinhibition is involved in the processing of tinnitus-related neuronal activity.

  8. Spontaneous tension haemopneumothorax.

    PubMed

    Patterson, Benjamin Oliver; Itam, Sarah; Probst, Fey

    2008-10-31

    We present a patient with sudden onset progressive shortness of breath and no history of trauma, who rapidly became haemodynamically compromised with a pneumothorax and pleural effusion seen on chest radiograph. He was treated for spontaneous tension pneumothorax but this was soon revealed to be a tension haemopneumothorax. He underwent urgent thoracotomy after persistent bleeding to explore an apical vascular abnormality seen on CT scanning. To our knowledge this is the first such case reported.Aetiology and current approach to spontaneous haemothorax are discussed briefly.

  9. Spontaneous and evoked release are independently regulated at individual active zones.

    PubMed

    Melom, Jan E; Akbergenova, Yulia; Gavornik, Jeffrey P; Littleton, J Troy

    2013-10-30

    Neurotransmitter release from synaptic vesicle fusion is the fundamental mechanism for neuronal communication at synapses. Evoked release following an action potential has been well characterized for its function in activating the postsynaptic cell, but the significance of spontaneous release is less clear. Using transgenic tools to image single synaptic vesicle fusion events at individual release sites (active zones) in Drosophila, we characterized the spatial and temporal dynamics of exocytotic events that occur spontaneously or in response to an action potential. We also analyzed the relationship between these two modes of fusion at single release sites. A majority of active zones participate in both modes of fusion, although release probability is not correlated between the two modes of release and is highly variable across the population. A subset of active zones is specifically dedicated to spontaneous release, indicating a population of postsynaptic receptors is uniquely activated by this mode of vesicle fusion. Imaging synaptic transmission at individual release sites also revealed general rules for spontaneous and evoked release, and indicate that active zones with similar release probability can cluster spatially within individual synaptic boutons. These findings suggest neuronal connections contain two information channels that can be spatially segregated and independently regulated to transmit evoked or spontaneous fusion signals.

  10. Intra-regional and inter-regional abnormalities and cognitive control deficits in young adult smokers.

    PubMed

    Feng, Dan; Yuan, Kai; Li, Yangding; Cai, Chenxi; Yin, Junsen; Bi, Yanzhi; Cheng, Jiadong; Guan, Yanyan; Shi, Sha; Yu, Dahua; Jin, Chenwang; Lu, Xiaoqi; Qin, Wei; Tian, Jie

    2016-06-01

    Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments.

  11. Spontaneous running activity in male rats - Effect of age

    NASA Technical Reports Server (NTRS)

    Mondon, C. E.; Dolkas, C. B.; Sims, C.; Reaven, G. M.

    1985-01-01

    Variations in the intensity and the patterns of spontaneous running activity in wheel cages were studied in male rats aged 7 weeks to one year. Daily running records were obtained for periods of 12 mo, and 24-hour recordings were made for selected runners in order to study variations in running activity during the day. The data indicate that for rats running over two miles/day, the maximum running intensity can be divided into two groups: a group of high achievers running 8 miles/day; and a group of moderate achievers running 4.8 miles/day. For both groups spontaneous activity reached a maximum after 4-5 weeks. An hourly pattern of running activity during the day was identified in rats of increasing age who averaged 9.0, 4.5, 2.6, and 1.2 miles/day, respectively. Progressive losses were observed in both the speed and the duration of spontaneous running as the rats increased in age, with the intensity of exercise falling below 2 miles/day after 7-8 months of age.

  12. Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature.

    PubMed

    Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

    2012-09-01

    Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K(+) channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1(V408A/+)). Here, we investigated the neuromuscular transmission of Kv1.1(V408A/+) ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve-muscle from Kv1.1(+/+) and Kv1.1(V408A/+) mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca(2+) signals that occurred abnormally only in preparations dissected from Kv1.1(V408A/+) mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca(2+) homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K(+) channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during

  13. Kv1.1 knock-in ataxic mice exhibit spontaneous myokymic activity exacerbated by fatigue, ischemia and low temperature

    PubMed Central

    Brunetti, Orazio; Imbrici, Paola; Botti, Fabio Massimo; Pettorossi, Vito Enrico; D'Adamo, Maria Cristina; Valentino, Mario; Zammit, Christian; Mora, Marina; Gibertini, Sara; Di Giovanni, Giuseppe; Muscat, Richard; Pessia, Mauro

    2012-01-01

    Episodic ataxia type 1 (EA1) is an autosomal dominant neurological disorder characterized by myokymia and attacks of ataxic gait often precipitated by stress. Several genetic mutations have been identified in the Shaker-like K+ channel Kv1.1 (KCNA1) of EA1 individuals, including V408A, which result in remarkable channel dysfunction. By inserting the heterozygous V408A, mutation in one Kv1.1 allele, a mouse model of EA1 has been generated (Kv1.1V408A/+). Here, we investigated the neuromuscular transmission of Kv1.1V408A/+ ataxic mice and their susceptibility to physiologically relevant stressors. By using in vivo preparations of lateral gastrocnemius (LG) nerve–muscle from Kv1.1+/+ and Kv1.1V408A/+ mice, we show that the mutant animals exhibit spontaneous myokymic discharges consisting of repeated singlets, duplets or multiplets, despite motor nerve axotomy. Two-photon laser scanning microscopy from the motor nerve, ex vivo, revealed spontaneous Ca2 + signals that occurred abnormally only in preparations dissected from Kv1.1V408A/+ mice. Spontaneous bursting activity, as well as that evoked by sciatic nerve stimulation, was exacerbated by muscle fatigue, ischemia and low temperatures. These stressors also increased the amplitude of compound muscle action potential. Such abnormal neuromuscular transmission did not alter fiber type composition, neuromuscular junction and vascularization of LG muscle, analyzed by light and electron microscopy. Taken together these findings provide direct evidence that identifies the motor nerve as an important generator of myokymic activity, that dysfunction of Kv1.1 channels alters Ca2 + homeostasis in motor axons, and also strongly suggest that muscle fatigue contributes more than PNS fatigue to exacerbate the myokymia/neuromyotonia phenotype. More broadly, this study points out that juxtaparanodal K+ channels composed of Kv1.1 subunits exert an important role in dampening the excitability of motor nerve axons during fatigue or

  14. A BDNF loop-domain mimetic acutely reverses spontaneous apneas and respiratory abnormalities during behavioral arousal in a mouse model of Rett syndrome

    PubMed Central

    Kron, Miriam; Lang, Min; Adams, Ian T.; Sceniak, Michael; Longo, Frank; Katz, David M.

    2014-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) are thought to contribute to the pathophysiology of Rett syndrome (RTT), a severe neurodevelopmental disorder caused by loss-of-function mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). In Mecp2 mutant mice, BDNF deficits have been associated with breathing abnormalities, a core feature of RTT, as well as with synaptic hyperexcitability within the brainstem respiratory network. Application of BDNF can reverse hyperexcitability in acute brainstem slices from Mecp2-null mice, suggesting that therapies targeting BDNF or its receptor, TrkB, could be effective at acute reversal of respiratory abnormalities in RTT. Therefore, we examined the ability of LM22A-4, a small-molecule BDNF loop-domain mimetic and TrkB partial agonist, to modulate synaptic excitability within respiratory cell groups in the brainstem nucleus tractus solitarius (nTS) and to acutely reverse abnormalities in breathing at rest and during behavioral arousal in Mecp2 mutants. Patch-clamp recordings in Mecp2-null brainstem slices demonstrated that LM22A-4 decreases excitability at primary afferent synapses in the nTS by reducing the amplitude of evoked excitatory postsynaptic currents and the frequency of spontaneous and miniature excitatory postsynaptic currents. In vivo, acute treatment of Mecp2-null and -heterozygous mutants with LM22A-4 completely eliminated spontaneous apneas in resting animals, without sedation. Moreover, we demonstrate that respiratory dysregulation during behavioral arousal, a feature of human RTT, is also reversed in Mecp2 mutants by acute treatment with LM22A-4. Together, these data support the hypothesis that reduced BDNF signaling and respiratory dysfunction in RTT are linked, and establish the proof-of-concept that treatment with a small-molecule structural mimetic of a BDNF loop domain and a TrkB partial agonist can acutely reverse abnormal breathing at rest and in response to behavioral arousal

  15. Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland.

    PubMed

    Chakrabarty, Basu; Dey, Anupa; Lam, Michelle; Ventura, Sabatino; Exintaris, Betty

    2015-06-01

    To examine the effects of the α1A -adrenoceptor antagonist, tamsulosin, on spontaneous contractile and electrical activity in the guinea-pig prostate gland. The effects of tamsulosin (0.1 and 0.3 nM) were investigated in adult and ageing male guinea pig prostate glands using conventional tension recording and electrophysiological intracellular microelectrode recording techniques. Tamsulosin reduced spontaneous activity, and had different age-dependent effects on adult and ageing guinea pigs at different concentrations. 0.1 nM tamsulosin caused a significantly greater reduction of spontaneous contractile and electrical activity in ageing guinea pigs in comparison to adult guinea pigs. In contrast, 0.3 nM tamsulosin had a significantly greater reduction of spontaneous contractile and electrical activity in adult guinea pigs in comparison to ageing guinea pigs. This study demonstrates that tamsulosin can modulate spontaneous myogenic stromal contractility and the underlying spontaneous electrical activity; tamsulosin does not block spontaneous activity. This reduction in spontaneous activity suggests that downstream cellular mechanisms underlying smooth muscle tone are being targeted, and these may represent novel therapeutic targets to better treat benign prostatic hyperplasia. © 2014 Wiley Periodicals, Inc.

  16. The emergence of spontaneous activity in neuronal cultures

    NASA Astrophysics Data System (ADS)

    Orlandi, J. G.; Alvarez-Lacalle, E.; Teller, S.; Soriano, J.; Casademunt, J.

    2013-01-01

    In vitro neuronal networks of dissociated hippocampal or cortical tissues are one of the most attractive model systems for the physics and neuroscience communities. Cultured neurons grow and mature, develop axons and dendrites, and quickly connect to their neighbors to establish a spontaneously active network within a week. The resulting neuronal network is characterized by a combination of excitatory and inhibitory neurons coupled through synaptic connections that interact in a highly nonlinear manner. The nonlinear behavior emerges from the dynamics of both the neurons' spiking activity and synaptic transmission, together with biological noise. These ingredients give rise to a rich repertoire of phenomena that are still poorly understood, including the emergence and maintenance of periodic spontaneous activity, avalanches, propagation of fronts and synchronization. In this work we present an overview on the rich activity of cultured neuronal networks, and detail the minimal theoretical considerations needed to describe experimental observations.

  17. Noise-induced effects on multicellular biopacemaker spontaneous activity: Differences between weak and strong pacemaker cells

    NASA Astrophysics Data System (ADS)

    Aghighi, Alireza; Comtois, Philippe

    2017-09-01

    Self-organization of spontaneous activity of a network of active elements is important to the general theory of reaction-diffusion systems as well as for pacemaking activity to initiate beating of the heart. Monolayer cultures of neonatal rat ventricular myocytes, consisting of resting and pacemaker cells, exhibit spontaneous activation of their electrical activity. Similarly, one proposed approach to the development of biopacemakers as an alternative to electronic pacemakers for cardiac therapy is based on heterogeneous cardiac cells with resting and spontaneously beating phenotypes. However, the combined effect of pacemaker characteristics, density, and spatial distribution of the pacemaker cells on spontaneous activity is unknown. Using a simple stochastic pattern formation algorithm, we previously showed a clear nonlinear dependency of spontaneous activity (occurrence and amplitude of spontaneous period) on the spatial patterns of pacemaker cells. In this study, we show that this behavior is dependent on the pacemaker cell characteristics, with weaker pacemaker cells requiring higher density and larger clusters to sustain multicellular activity. These multicellular structures also demonstrated an increased sensitivity to voltage noise that favored spontaneous activity at lower density while increasing temporal variation in the period of activity. This information will help researchers overcome the current limitations of biopacemakers.

  18. Spontaneous cortical activity alternates between motifs defined by regional axonal projections

    PubMed Central

    Mohajerani, Majid H.; Chan, Allen W.; Mohsenvand, Mostafa; LeDue, Jeffrey; Liu, Rui; McVea, David A.; Boyd, Jamie D.; Wang, Yu Tian; Reimers, Mark; Murphy, Timothy H.

    2014-01-01

    In lightly anaesthetized or awake adult mice using millisecond timescale voltage sensitive dye imaging, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing including vision, audition, and touch. Similar cortical networks were found with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality specific sources such as primary sensory areas, and a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area, and a secondary anterior medial sink within the cingulate/secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range mono-synaptic connections between cortical regions. Maps of intracortical mono-synaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity. PMID:23974708

  19. Tansig activation function (of MLP network) for cardiac abnormality detection

    NASA Astrophysics Data System (ADS)

    Adnan, Ja'afar; Daud, Nik Ghazali Nik; Ishak, Mohd Taufiq; Rizman, Zairi Ismael; Rahman, Muhammad Izzuddin Abd

    2018-02-01

    Heart abnormality often occurs regardless of gender, age and races. This problem sometimes does not show any symptoms and it can cause a sudden death to the patient. In general, heart abnormality is the irregular electrical activity of the heart. This paper attempts to develop a program that can detect heart abnormality activity through implementation of Multilayer Perceptron (MLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP network by using several training algorithms with Tansig activation function.

  20. Spectral changes in spontaneous MEG activity across the lifespan

    NASA Astrophysics Data System (ADS)

    Gómez, Carlos; Pérez-Macías, Jose M.; Poza, Jesús; Fernández, Alberto; Hornero, Roberto

    2013-12-01

    Objective. The aim of this study is to explore the spectral patterns of spontaneous magnetoencephalography (MEG) activity across the lifespan. Approach. Relative power (RP) in six frequency bands (delta, theta, alpha, beta-1, beta-2 and gamma) was calculated in a sample of 220 healthy subjects with ages ranging from 7 to 84 years. Main results. A significant RP decrease in low-frequency bands (i.e. delta and theta) and a significant increase in high bands (mainly beta-1 and beta-2) were found from childhood to adolescence. This trend was observed until the sixth decade of life, though only slight changes were found. Additionally, healthy aging was characterized by a power increase in low-frequency bands. Our results show that spectral changes across the lifespan may follow a quadratic relationship in delta, theta, alpha, beta-2 and gamma bands with peak ages being reached around the fifth or sixth decade of life. Significance. Our findings provide original insights into the definition of the ‘normal’ behavior of age-related MEG spectral patterns. Furthermore, our study can be useful for the forthcoming MEG research focused on the description of the abnormalities of different brain diseases in comparison to cognitive decline in normal aging.

  1. Effect of hyperthyroidism on spontaneous physical activity and energy expenditure in rats.

    PubMed

    Levine, James A; Nygren, Jonas; Short, Kevin R; Nair, K Sreekumaran

    2003-01-01

    Thyroid hormone excess is associated with increased energy expenditure. The contributions of increases in spontaneous physical activity and nonexercise activity thermogenesis (NEAT) to this effect have not been defined. To address the hypothesis that hyperthyroidism is associated with increased spontaneous physical activity and NEAT, we rendered rats hyperthyroid by using continuous infusion of high-dose triiodothyronine for 14 days and measured the effects on physical activity and NEAT. On day 14, in the hyperthyroid group the mean +/- SD triiodothyronine concentration was 755 +/- 137 (range 574-919) ng/dl and in the control group 59 +/- 0.5 (58-59) ng/dl. Over the 14-day treatment period, mean spontaneous physical activity increased in the hyperthyroid rats from 24 +/- 7 to 36 +/- 6 activity units (AU)/min; P < 0.001 but did not increase in the controls (23 +/- 7 vs. 22 +/- 4 AU/min). Also, over the 14-day period, daily NEAT increased in the hyperthyroid rats from 8.1 +/- 2.8 to 19.7 +/- 5.0 kcal/day (P < 0.001) but did not increase in the controls (8.7 +/- 3.5 cf 9.4 +/- 1.7 kcal/day; not significant). In conclusion, hyperthyroidism is associated with increased spontaneous physical activity and NEAT.

  2. Presbycusis Disrupts Spontaneous Activity Revealed by Resting-State Functional MRI

    PubMed Central

    Chen, Yu-Chen; Chen, Huiyou; Jiang, Liang; Bo, Fan; Xu, Jin-Jing; Mao, Cun-Nan; Salvi, Richard; Yin, Xindao; Lu, Guangming; Gu, Jian-Ping

    2018-01-01

    Purpose: Presbycusis, age-related hearing loss, is believed to involve neural changes in the central nervous system, which is associated with an increased risk of cognitive impairment. The goal of this study was to determine if presbycusis disrupted spontaneous neural activity in specific brain areas involved in auditory processing, attention and cognitive function using resting-state functional magnetic resonance imaging (fMRI) approach. Methods: Hearing and resting-state fMRI measurements were obtained from 22 presbycusis patients and 23 age-, sex- and education-matched healthy controls. To identify changes in spontaneous neural activity associated with age-related hearing loss, we compared the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of fMRI signals in presbycusis patients vs. controls and then determined if these changes were linked to clinical measures of presbycusis. Results: Compared with healthy controls, presbycusis patients manifested decreased spontaneous activity mainly in the superior temporal gyrus (STG), parahippocampal gyrus (PHG), precuneus and inferior parietal lobule (IPL) as well as increased neural activity in the middle frontal gyrus (MFG), cuneus and postcentral gyrus (PoCG). A significant negative correlation was observed between ALFF/ReHo activity in the STG and average hearing thresholds in presbycusis patients. Increased ALFF/ReHo activity in the MFG was positively correlated with impaired Trail-Making Test B (TMT-B) scores, indicative of impaired cognitive function involving the frontal lobe. Conclusions: Presbycusis patients have disrupted spontaneous neural activity reflected by ALFF and ReHo measurements in several brain regions; these changes are associated with specific cognitive performance and speech/language processing. These findings mainly emphasize the crucial role of aberrant resting-state ALFF/ReHo patterns in presbycusis patients and will lead to a better understanding of the

  3. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities.

    PubMed

    McNally, James M; McCarley, Robert W

    2016-05-01

    We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention.

  4. Gamma band oscillations: a key to understanding schizophrenia symptoms and neural circuit abnormalities

    PubMed Central

    McNally, James M.; McCarley, Robert W.

    2016-01-01

    Purpose of review We review our current understanding of abnormal γ band oscillations in schizophrenia, their association with symptoms and the underlying cortical circuit abnormality, with a particular focus on the role of fast-spiking parvalbumin gamma-aminobutyric acid (GABA) neurons in the disease state. Recent findings Clinical electrophysiological studies of schizophrenia patients and pharmacological models of the disorder show an increase in spontaneous γ band activity (not stimulus-evoked) measures. These findings provide a crucial link between preclinical and clinical work examining the role of γ band activity in schizophrenia. MRI-based experiments measuring cortical GABA provides evidence supporting impaired GABAergic neurotransmission in schizophrenia patients, which is correlated with γ band activity level. Several studies suggest that stimulation of the cortical circuitry, directly or via subcortical structures, has the potential to modulate cortical γ activity, and improve cognitive function. Summary Abnormal γ band activity is observed in patients with schizophrenia and disease models in animals, and is suggested to underlie the psychosis and cognitive/perceptual deficits. Convergent evidence from both clinical and preclinical studies suggest the central factor in γ band abnormalities is impaired GABAergic neurotransmission, particularly in a subclass of neurons which express parvalbumin. Rescue of γ band abnormalities presents an intriguing option for therapeutic intervention. PMID:26900672

  5. Sensory memory for odors is encoded in spontaneous correlated activity between olfactory glomeruli.

    PubMed

    Galán, Roberto F; Weidert, Marcel; Menzel, Randolf; Herz, Andreas V M; Galizia, C Giovanni

    2006-01-01

    Sensory memory is a short-lived persistence of a sensory stimulus in the nervous system, such as iconic memory in the visual system. However, little is known about the mechanisms underlying olfactory sensory memory. We have therefore analyzed the effect of odor stimuli on the first odor-processing network in the honeybee brain, the antennal lobe, which corresponds to the vertebrate olfactory bulb. We stained output neurons with a calcium-sensitive dye and measured across-glomerular patterns of spontaneous activity before and after a stimulus. Such a single-odor presentation changed the relative timing of spontaneous activity across glomeruli in accordance with Hebb's theory of learning. Moreover, during the first few minutes after odor presentation, correlations between the spontaneous activity fluctuations suffice to reconstruct the stimulus. As spontaneous activity is ubiquitous in the brain, modifiable fluctuations could provide an ideal substrate for Hebbian reverberations and sensory memory in other neural systems.

  6. Investigation of the activation of the temporalis and masseter muscles in voluntary and spontaneous smile production.

    PubMed

    Steele, Jessica E; Woodcock, Ian R; Murphy, Adrian D; Ryan, Monique M; Penington, Tony J; Coombs, Christopher J

    2018-07-01

    Masticatory muscles or their nerve supply are options for facial reanimation surgery, but their ability to create spontaneous smile has been questioned. This study assessed the percentage of healthy adults who activate the temporalis and masseter muscles during voluntary and spontaneous smile. Healthy volunteer adults underwent electromyography (EMG) studies of the temporalis and masseter muscles during voluntary and spontaneous smile. Responses were repeated three times and recorded as negative, weakly positive, or strongly positive according to the activity observed. The best response was used for analysis. Thirty healthy adults (median age: 34 years, range: 25-69 years) participated. Overall, 92% of the masseter muscles were activated during voluntary smile (22% strong, 70% weak). Seventy-seven percent of the masseter muscles were activated in spontaneous smile (12% strong, 65% weak). The temporalis muscle was activated in 62% of responses in voluntary smile (15% strong, 47% weak) and in 45% of responses in spontaneous smile (13% strong, 32% weak). No significant difference was found for males vs females or closed vs open mouth smiles. There was no significant difference in responses between voluntary and spontaneous smiles for the temporalis and masseter muscles, and their use in voluntary smile did not predict activity in spontaneous smile. Our study has shown that masseter and temporalis are active in a high proportion of healthy adults during voluntary and spontaneous smiles. Further work is required to determine the relationship between preoperative donor muscle activation and postoperative spontaneous smile, and whether masticatory muscle activity can be upregulated with appropriate training. Copyright © 2018. Published by Elsevier Ltd.

  7. Treatment of abnormal vaginal flora in early pregnancy with clindamycin for the prevention of spontaneous preterm birth: a systematic review and metaanalysis

    PubMed Central

    Lamont, Ronald F.; Nhan-Chang, Chia-Ling; Sobel, Jack D.; Workowski, Kimberly; Conde-Agudelo, Agustin; Romero, Roberto

    2011-01-01

    The purpose of this study was to determine whether the administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation reduces the risk of preterm birth and late miscarriage. We conducted a systematic review and metaanalysis of randomized controlled trials of the early administration of clindamycin to women with abnormal vaginal flora at <22 weeks of gestation. Five trials that comprised 2346 women were included. Clindamycin that was administered at <22 weeks of gestation was associated with a significantly reduced risk of preterm birth at <37 weeks of gestation and late miscarriage. There were no overall differences in the risk of preterm birth at <33 weeks of gestation, low birthweight, very low birthweight, admission to neonatal intensive care unit, stillbirth, peripartum infection, and adverse effects. Clindamycin in early pregnancy in women with abnormal vaginal flora reduces the risk of spontaneous preterm birth at <37 weeks of gestation and late miscarriage. There is evidence to justify further randomized controlled trials of clindamycin for the prevention of preterm birth. However, a deeper understanding of the vaginal microbiome, mucosal immunity, and the biology of bacterial vaginosis will be needed to inform the design of such trials. PMID:22071048

  8. Endocrine dysfunction and recurrent spontaneous abortion: An overview

    PubMed Central

    Kaur, Ramandeep; Gupta, Kapil

    2016-01-01

    Miscarriage is the spontaneous loss of a fetus before it is viable, occurring at a rate of 15–20%. Recurrent spontaneous abortion (RSA) or habitual miscarriage is defined as repeated occurrence of 3 or more miscarriages before 20th week of gestation accounting for the most common complication of early pregnancy in humans. Various etiological factors responsible for recurrent miscarriage are anatomical, genetical, endocrinological, immunological, and infectious. The endocrinological abnormalities may be polycystic ovarian syndrome, hyperprolactinemia, luteal phase defect, thyroid dysfunction, diabetes, or hyperandrogenism contributing to recurrent pregnancy loss. In the present article, the role of endocrinological disorders in patients with RSA has been reviewed. The article search was done using electronic databases, Google scholarly articles, and PubMed based on different key words. We have further combined the searches and made grouping as per various endocrine abnormalities, which might be responsible to cause spontaneous loss of fetus. PMID:27127734

  9. dSir2 mediates the increased spontaneous physical activity in flies on calorie restriction.

    PubMed

    Parashar, Vijay; Rogina, Blanka

    2009-06-22

    Calorie restriction (CR) is the most effective way to increase life span and delay the onset of age-related symptoms in animals. We have previously reported that CR affects a variety of physiological phenotypes in flies and results in dramatic behavioral, physical and demographic changes. Here we show effects of low and high calorie levels on the spontaneous physical activity of flies. Wild type flies maintained on a low calorie diet exhibit higher spontaneous activity compared to flies on higher calorie diets. This increase is dependent on the presence of Sir2 since a low calorie diet does not increase the activity of dSir2 null flies. Similarly, increasing dSir2 activity by feeding flies resveratrol, a CR mimetic, increases spontaneous physical activity of flies on high caloric food. In Drosophila, spontaneous physical activity therefore closely mimics life span in its dependence on Sir2.

  10. Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs.

    PubMed

    Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

    2014-11-14

    To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity.

  11. Numerically abnormal chromosome constitutions in humans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  12. Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats.

    PubMed

    Kaegi, Sibille; Schwab, Martin E; Dietz, Volker; Fouad, Karim

    2002-07-01

    This investigation was designed to study the spontaneous functional recovery of adult rats with incomplete spinal cord injury (SCI) at thoracic level during a time course of 2 weeks. Daily testing sessions included open field locomotor examination and electromyographic (EMG) recordings from a knee extensor (vastus lateralis, VL) and an ankle flexor muscle (tibialis anterior, TA) in the hindlimbs of treadmill walking rats. The BBB score (a locomotor score named after Basso et al., 1995, J. Neurotrauma, 12, 1-21) and various measures from EMG recordings were analysed (i.e. step cycle duration, rhythmicity of limb movements, flexor and extensor burst duration, EMG amplitude, root-mean-square, activity overlap between flexor and extensor muscles and hindlimb coupling). Directly after SCI, a marked drop in locomotor ability occurred in all rats with subsequent partial recovery over 14 days. The recovery was most pronounced during the first week. Significant changes were noted in the recovery of almost all analysed EMG measures. Within the 14 days of recovery, many of these measures approached control levels. Persistent abnormalities included a prolonged flexor burst and increased activity overlap between flexor and extensor muscles. Activity overlap between flexor and extensor muscles might be directly caused by altered descending input or by maladaptation of central pattern generating networks and/or sensory feedback.

  13. Measuring frequency of spontaneous swallowing.

    PubMed

    Afkari, Sohail

    2007-12-01

    A new multi-sensory non-invasive portable system capable of detecting spontaneous swallowing in a patient population has been developed. Swallowing signals are recorded via Electromyogram (voltage potentials generated by throat muscles), an accelerometer (laryngeal elevations) and a microphone (cervical auscultation) affixed to the neck at the coniotomy region. Simultaneous signal comparison of all three modalities provides a vastly more reliable measure of swallowing frequency by rejecting artefacts associated with speech, body movement, coughing and background intereferences. The operational accuracy of the system was validated by a hand-held manual counter on a healthy subject undertaking everyday activities. Preliminary results showed a recorded mean spontaneous swallowing frequency of 1.32 swallows/minute and a slighly higher mean voluntary swallowing frequency of 1.52 swallows/minute with the intake of 100 ml of water. The device was able to detect 94.3% of dry swallows correctly, with each sensor responding differently to various noise interferences. The proposed system has potential to provide additional diagnostic information in clinical research of possible physiological problems associated with an abnormal swallowing frequency across a range of medical fields.

  14. Abnormal Reward System Activation in Mania

    PubMed Central

    Abler, Birgit; Greenhouse, Ian; Ongur, Dost; Walter, Henrik; Heckers, Stephan

    2008-01-01

    Transmission of reward signals is a function of dopamine, a neurotransmitter known to be involved in the mechanism of psychosis. Using functional magnetic resonance imaging (fMRI), we investigated how expectation and receipt of monetary rewards modulate brain activation in patients with bipolar mania and schizophrenia. We studied 12 acutely manic patients with a history of bipolar disorder, 12 patients with a current episode of schizoaffective disorder or schizophrenia and 12 healthy subjects. All patients were treated with dopamine antagonists at the time of the study. Subjects performed a delayed incentive paradigm with monetary reward in the scanner that allowed for investigating effects of expectation, receipt, and omission of rewards. Patients with schizophrenia and healthy control subjects showed the expected activation of dopaminergic brain areas, that is, ventral tegmentum activation upon expectation of monetary rewards and nucleus accumbens activation during receipt vs omission of rewards. In manic patients, however, we did not find a similar pattern of brain activation and the differential signal in the nucleus accumbens upon receipt vs omission of rewards was significantly lower compared to the healthy control subjects. Our findings provide evidence for abnormal function of the dopamine system during receipt or omission of expected rewards in bipolar disorder. These deficits in prediction error processing in acute mania may help to explain symptoms of disinhibition and abnormal goal pursuit regulation. PMID:17987058

  15. Mechanism of gastrointestinal abnormal motor activity induced by cisplatin in conscious dogs

    PubMed Central

    Ando, Hiroyuki; Mochiki, Erito; Ohno, Tetsuro; Yanai, Mitsuhiro; Toyomasu, Yoshitaka; Ogata, Kyoichi; Tabe, Yuichi; Aihara, Ryuusuke; Nakabayashi, Toshihiro; Asao, Takayuki; Kuwano, Hiroyuki

    2014-01-01

    AIM: To investigate whether 5-hydroxytryptamine (serotonin; 5-HT) is involved in mediating abnormal motor activity in dogs after cisplatin administration. METHODS: After the dogs had been given a 2-wk recovery period, all of them were administered cisplatin, and the motor activity was recorded using strain gauge force transducers. Blood and intestinal fluid samples were collected to measure 5-HT for 24 h. To determine whether 5-HT in plasma or that in intestinal fluids is more closely related to abnormal motor activity we injected 5-HT into the bloodstream and the intestinal tract of the dogs. RESULTS: Cisplatin given intravenously produced abnormal motor activity that lasted up to 5 h. From 3 to 4 h after cisplatin administration, normal intact dogs exhibited retropropagation of motor activity accompanied by emesis. The concentration of 5-HT in plasma reached the peak at 4 h, and that in intestinal fluids reached the peak at 3 h. In normal intact dogs with resection of the vagus nerve that were administered kytril, cisplatin given intravenously did not produce abnormal motor activity. Intestinal serotonin administration did not produce abnormal motor activity, but intravenous serotonin administration did. CONCLUSION: After the intravenous administration of cisplatin, abnormal motor activity was produced in the involved vagus nerve and in the involved serotonergic neurons via another pathway. This study was the first to determine the relationship between 5-HT and emesis-induced motor activity. PMID:25400453

  16. Spontaneous Division and Motility in Active Nematic Droplets

    NASA Astrophysics Data System (ADS)

    Giomi, Luca; DeSimone, Antonio

    2014-04-01

    We investigate the mechanics of an active droplet endowed with internal nematic order and surrounded by an isotropic Newtonian fluid. Using numerical simulations we demonstrate that, due to the interplay between the active stresses and the defective geometry of the nematic director, this system exhibits two of the fundamental functions of living cells: spontaneous division and motility, by means of self-generated hydrodynamic flows. These behaviors can be selectively activated by controlling a single physical parameter, namely, an active variant of the capillary number.

  17. Neuronal activity related to spontaneous and capsaicin-induced rhythmical jaw movements in the rat.

    PubMed

    Ohta, M; Sasamoto, K; Kobayashi, J

    1998-02-01

    Intraoral capsaicin induced rhythmical jaw movements (RJM) in anesthetized rats. Neurons in the trigeminal spinal nucleus caudalis or the cortico-peduncular (CP) axons were extracellularly recorded. Capsaicin excited dose-dependently most caudalis neurons, which were activated by stimulation of the oral cavity and/or the tooth pulp and activated during spontaneous or induced RJM. Ten of 55 CP axons were antidromically activated by stimulation of the contralateral trigeminal motor nucleus. All antidromic and 29 other CP axons discharged prior to the spontaneous RJM, but most of them did not during capsaicin-induced RJM. These neuronal activities possibly initiate spontaneous RJM although the activities of caudalis neurons are necessary for capsicin-induced RJM.

  18. Diabetes attenuates urothelial modulation of detrusor contractility and spontaneous activity.

    PubMed

    Wang, Yi; Tar, Moses T; Fu, Shibo; Melman, Arnold; Davies, Kelvin P

    2014-10-01

    To investigate the effect of diabetes on urothelial modulation of bladder contractility. Bladder strips (urothelium intact or denuded) were prepared from 8-week-old streptozotocin-induced diabetic (n = 19) and non-diabetic control rats (n = 10). The effect of modulators of MaxiK (iberiotoxin and tetraethylammonium) and Kv7 (XE991 and retigabine) potassium channel activity were investigated for their effects on both carbachol-induced force generation and spontaneous contractile activity. In bladder strips from non-diabetic animals, the presence of the urothelium resulted in marked sensitivity to carbachol-induced force generation by modulators of MaxiK and Kv7 channel activity, whereas in the diabetic animal urothelial sensitivity to these agents was significantly diminished. Urothelial-intact bladder strips from non-diabetic animals were more sensitive to modulators of Kv7 activity in reducing the amplitude of spontaneous phasic contractions than urothelial-denuded bladder strips, whereas in diabetic animals the presence or absence of the urothelium did not alter the sensitivity to modulators of Kv7 activity. Spontaneous activity in the presence of tetraethylammonium was not affected by the urothelium in bladder strips from either diabetic or non-diabetic animals. The presence of the urothelium in bladders from non-diabetic animals modulates the activity of potassium blockers to affect bladder contractility, whereas in the diabetic bladder this effect is attenuated. These findings could help to explain the lack of success of pharmaceutical treatments targeting potassium channels to treat bladder pathology in patients with diseases imparing urothelial function. © 2014 The Japanese Urological Association.

  19. Abnormal folate metabolism as a risk factor for first-trimester spontaneous abortion.

    PubMed

    Hoffman, Michael L; Scoccia, Bert; Kurczynski, Thaddeus W; Shulman, Lee P; Gao, Weihua

    2008-03-01

    To assess the potential role of folic acid in early pregnancy loss by measuring homocysteine (hcy) levels in healthy, pregnant women who present with a current first-trimester miscarriage. This was a cross-sectional analysis comprising 13 patients aged 18-31 years old who had a scheduled dilatation and curettage for a first-trimester miscarriage. The controls were 15 patients of similar maternal age presenting for a first-trimester prenatal care visit. Following completion of a 21-item, structured questionnaire, patients were excluded from the study if they had any known risk factors for a first-trimester miscarriage. The remaining patients provided blood samples for measurement of homocysteine and red blood cell folate. Cases and controls were compared using a standard 2-sample t test. In order to detect a clinically relevant 2.3 micromol/L difference in homocysteine levels, 11 cases and 8 controls were needed. The mean hcy level in cases (5.8 umolmol/L) vs. controls (5.7 micromol/L) was not significantly different (p = 0.83), and all individual values fell within the normal range expected in pregnant women. Red blood cell folate levels (cases=586 ng/mL, controls=611 ng/mL) were also not significantly different (p = 0.72), and no cases of folate deficiency were detected. Maternal age (cases=26, controls=25) and gestational age (cases = 8.8 weeks, controls = 8.4 weeks) were similar between the 2 groups. In this community-based pilot study, abnormal folate metabolism was not an apparent risk factor for spontaneous first-trimester pregnancy loss.

  20. Synchronization of Spontaneous Active Motility of Hair Cell Bundles

    PubMed Central

    Zhang, Tracy-Ying; Ji, Seung; Bozovic, Dolores

    2015-01-01

    Hair cells of the inner ear exhibit an active process, believed to be crucial for achieving the sensitivity of auditory and vestibular detection. One of the manifestations of the active process is the occurrence of spontaneous hair bundle oscillations in vitro. Hair bundles are coupled by overlying membranes in vivo; hence, explaining the potential role of innate bundle motility in the generation of otoacoustic emissions requires an understanding of the effects of coupling on the active bundle dynamics. We used microbeads to connect small groups of hair cell bundles, using in vitro preparations that maintain their innate oscillations. Our experiments demonstrate robust synchronization of spontaneous oscillations, with either 1:1 or multi-mode phase-locking. The frequency of synchronized oscillation was found to be near the mean of the innate frequencies of individual bundles. Coupling also led to an improved regularity of entrained oscillations, demonstrated by an increase in the quality factor. PMID:26540409

  1. Altered spontaneous brain activity pattern in patients with late monocular blindness in middle-age using amplitude of low-frequency fluctuation: a resting-state functional MRI study.

    PubMed

    Li, Qing; Huang, Xin; Ye, Lei; Wei, Rong; Zhang, Ying; Zhong, Yu-Lin; Jiang, Nan; Shao, Yi

    2016-01-01

    Previous reports have demonstrated significant brain activity changes in bilateral blindness, whereas brain activity changes in late monocular blindness (MB) at rest are not well studied. Our study aimed to investigate spontaneous brain activity in patients with late middle-aged MB using the amplitude of low-frequency fluctuation (ALFF) method and their relationship with clinical features. A total of 32 patients with MB (25 males and 7 females) and 32 healthy control (HC) subjects (25 males and 7 females), similar in age, sex, and education, were recruited for the study. All subjects were performed with resting-state functional magnetic resonance imaging scanning. The ALFF method was applied to evaluate spontaneous brain activity. The relationships between the ALFF signal values in different brain regions and clinical features in MB patients were investigated using correlation analysis. Compared with HCs, the MB patients had marked lower ALFF values in the left cerebellum anterior lobe, right parahippocampal gyrus, right cuneus, left precentral gyrus, and left paracentral lobule, but higher ALFF values in the right middle frontal gyrus, left middle frontal gyrus, and left supramarginal gyrus. However, there was no linear correlation between the mean ALFF signal values in brain regions and clinical manifestations in MB patients. There were abnormal spontaneous activities in many brain regions including vision and vision-related regions, which might indicate the neuropathologic mechanisms of vision loss in the MB patients. Meanwhile, these brain activity changes might be used as a useful clinical indicator for MB.

  2. Increasing Spontaneous Retinal Activity before Eye Opening Accelerates the Development of Geniculate Receptive Fields

    PubMed Central

    Davis, Zachary W.; Chapman, Barbara

    2015-01-01

    Visually evoked activity is necessary for the normal development of the visual system. However, little is known about the capacity for patterned spontaneous activity to drive the maturation of receptive fields before visual experience. Retinal waves provide instructive retinotopic information for the anatomical organization of the visual thalamus. To determine whether retinal waves also drive the maturation of functional responses, we increased the frequency of retinal waves pharmacologically in the ferret (Mustela putorius furo) during a period of retinogeniculate development before eye opening. The development of geniculate receptive fields after receiving these increased neural activities was measured using single-unit electrophysiology. We found that increased retinal waves accelerate the developmental reduction of geniculate receptive field sizes. This reduction is due to a decrease in receptive field center size rather than an increase in inhibitory surround strength. This work reveals an instructive role for patterned spontaneous activity in guiding the functional development of neural circuits. SIGNIFICANCE STATEMENT Patterned spontaneous neural activity that occurs during development is known to be necessary for the proper formation of neural circuits. However, it is unknown whether the spontaneous activity alone is sufficient to drive the maturation of the functional properties of neurons. Our work demonstrates for the first time an acceleration in the maturation of neural function as a consequence of driving patterned spontaneous activity during development. This work has implications for our understanding of how neural circuits can be modified actively to improve function prematurely or to recover from injury with guided interventions of patterned neural activity. PMID:26511250

  3. Discharges of aortic and carotid sinus baroreceptors during spontaneous motor activity and pharmacologically evoked pressor interventions.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

    2014-07-01

    Our laboratory has demonstrated that the cardiomotor component of aortic baroreflex is temporarily inhibited at the onset of spontaneous motor activity in decerebrate cats, without altering carotid sinus baroreflex. A reason for this dissociation may be attributed to a difference in the responses between aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity. The stimulus-response curves of AoNA and CsNA against mean arterial blood pressure (MAP) were compared between the pressor interventions evoked by spontaneous motor activity and by intravenous administration of phenylephrine or norepinephrine, in which the responses in heart rate (HR) were opposite (i.e., tachycardia vs. baroreflex bradycardia), despite the identical increase in MAP of 34-40 mmHg. In parallel to the pressor response, mean AoNA and CsNA increased similarly by 78-81 and by 88 % of the baseline control, respectively, irrespective of whether the pressor response was evoked by spontaneous motor activity or by a pharmacological intervention. The slope of the stimulus-response curve of the mean AoNA became greater (P < 0.05) during spontaneous motor activity as compared to the pharmacological intervention. On the other hand, the stimulus-response curve of the mean CsNA and its slope were equal (P > 0.05) between the two pressor interventions. Furthermore, the slopes of the stimulus-response curves of both diastolic AoNA and CsNA (defined as the minimal value within a beat) exhibited a greater increase during spontaneous motor activity. All differences in the slopes of the stimulus-response curves were abolished by restraining HR at the intrinsic cardiac frequency. In conclusion, mean mass activities of both aortic and carotid sinus baroreceptors are able to encode the beat-by-beat changes in MAP not only at rest but also during spontaneous motor activity and spontaneous motor activity-related reduction of aortic baroreceptor activity is denied

  4. Aberrant Hyperconnectivity in the Motor System at Rest Is Linked to Motor Abnormalities in Schizophrenia Spectrum Disorders.

    PubMed

    Walther, Sebastian; Stegmayer, Katharina; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Viher, Petra V

    2017-09-01

    Motor abnormalities are frequently observed in schizophrenia and structural alterations of the motor system have been reported. The association of aberrant motor network function, however, has not been tested. We hypothesized that abnormal functional connectivity would be related to the degree of motor abnormalities in schizophrenia. In 90 subjects (46 patients) we obtained resting stated functional magnetic resonance imaging (fMRI) for 8 minutes 40 seconds at 3T. Participants further completed a motor battery on the scanning day. Regions of interest (ROI) were cortical motor areas, basal ganglia, thalamus and motor cerebellum. We computed ROI-to-ROI functional connectivity. Principal component analyses of motor behavioral data produced 4 factors (primary motor, catatonia and dyskinesia, coordination, and spontaneous motor activity). Motor factors were correlated with connectivity values. Schizophrenia was characterized by hyperconnectivity in 3 main areas: motor cortices to thalamus, motor cortices to cerebellum, and prefrontal cortex to the subthalamic nucleus. In patients, thalamocortical hyperconnectivity was linked to catatonia and dyskinesia, whereas aberrant connectivity between rostral anterior cingulate and caudate was linked to the primary motor factor. Likewise, connectivity between motor cortex and cerebellum correlated with spontaneous motor activity. Therefore, altered functional connectivity suggests a specific intrinsic and tonic neural abnormality in the motor system in schizophrenia. Furthermore, altered neural activity at rest was linked to motor abnormalities on the behavioral level. Thus, aberrant resting state connectivity may indicate a system out of balance, which produces characteristic behavioral alterations. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Computational Account of Spontaneous Activity as a Signature of Predictive Coding

    PubMed Central

    Koren, Veronika

    2017-01-01

    Spontaneous activity is commonly observed in a variety of cortical states. Experimental evidence suggested that neural assemblies undergo slow oscillations with Up ad Down states even when the network is isolated from the rest of the brain. Here we show that these spontaneous events can be generated by the recurrent connections within the network and understood as signatures of neural circuits that are correcting their internal representation. A noiseless spiking neural network can represent its input signals most accurately when excitatory and inhibitory currents are as strong and as tightly balanced as possible. However, in the presence of realistic neural noise and synaptic delays, this may result in prohibitively large spike counts. An optimal working regime can be found by considering terms that control firing rates in the objective function from which the network is derived and then minimizing simultaneously the coding error and the cost of neural activity. In biological terms, this is equivalent to tuning neural thresholds and after-spike hyperpolarization. In suboptimal working regimes, we observe spontaneous activity even in the absence of feed-forward inputs. In an all-to-all randomly connected network, the entire population is involved in Up states. In spatially organized networks with local connectivity, Up states spread through local connections between neurons of similar selectivity and take the form of a traveling wave. Up states are observed for a wide range of parameters and have similar statistical properties in both active and quiescent state. In the optimal working regime, Up states are vanishing, leaving place to asynchronous activity, suggesting that this working regime is a signature of maximally efficient coding. Although they result in a massive increase in the firing activity, the read-out of spontaneous Up states is in fact orthogonal to the stimulus representation, therefore interfering minimally with the network function. PMID:28114353

  6. Spontaneous cortical activity is transiently poised close to criticality

    PubMed Central

    Monier, Cyril; Kumar, Arvind; Deco, Gustavo; Frégnac, Yves

    2017-01-01

    Brain activity displays a large repertoire of dynamics across the sleep-wake cycle and even during anesthesia. It was suggested that criticality could serve as a unifying principle underlying the diversity of dynamics. This view has been supported by the observation of spontaneous bursts of cortical activity with scale-invariant sizes and durations, known as neuronal avalanches, in recordings of mesoscopic cortical signals. However, the existence of neuronal avalanches in spiking activity has been equivocal with studies reporting both its presence and absence. Here, we show that signs of criticality in spiking activity can change between synchronized and desynchronized cortical states. We analyzed the spontaneous activity in the primary visual cortex of the anesthetized cat and the awake monkey, and found that neuronal avalanches and thermodynamic indicators of criticality strongly depend on collective synchrony among neurons, LFP fluctuations, and behavioral state. We found that synchronized states are associated to criticality, large dynamical repertoire and prolonged epochs of eye closure, while desynchronized states are associated to sub-criticality, reduced dynamical repertoire, and eyes open conditions. Our results show that criticality in cortical dynamics is not stationary, but fluctuates during anesthesia and between different vigilance states. PMID:28542191

  7. Spontaneous cortical activity is transiently poised close to criticality.

    PubMed

    Hahn, Gerald; Ponce-Alvarez, Adrian; Monier, Cyril; Benvenuti, Giacomo; Kumar, Arvind; Chavane, Frédéric; Deco, Gustavo; Frégnac, Yves

    2017-05-01

    Brain activity displays a large repertoire of dynamics across the sleep-wake cycle and even during anesthesia. It was suggested that criticality could serve as a unifying principle underlying the diversity of dynamics. This view has been supported by the observation of spontaneous bursts of cortical activity with scale-invariant sizes and durations, known as neuronal avalanches, in recordings of mesoscopic cortical signals. However, the existence of neuronal avalanches in spiking activity has been equivocal with studies reporting both its presence and absence. Here, we show that signs of criticality in spiking activity can change between synchronized and desynchronized cortical states. We analyzed the spontaneous activity in the primary visual cortex of the anesthetized cat and the awake monkey, and found that neuronal avalanches and thermodynamic indicators of criticality strongly depend on collective synchrony among neurons, LFP fluctuations, and behavioral state. We found that synchronized states are associated to criticality, large dynamical repertoire and prolonged epochs of eye closure, while desynchronized states are associated to sub-criticality, reduced dynamical repertoire, and eyes open conditions. Our results show that criticality in cortical dynamics is not stationary, but fluctuates during anesthesia and between different vigilance states.

  8. [Risk factors in the living environment of early spontaneous abortion pregnant women].

    PubMed

    Liu, Xin-yan; Bian, Xu-ming; Han, Jing-xiu; Cao, Zhao-jin; Fan, Guang-sheng; Zhang, Chao; Zhang, Wen-li; Zhang, Shu-zhen; Sun, Xiao-guang

    2007-10-01

    To study the relationship between early spontaneous abortion and living environment, and explore the risk factors of spontaneous abortion. We conducted analysis based on the interview of 200 spontaneous abortion cases and the matched control (age +/- 2 years) by using multifactor Logistic regression analysis. The proportions of watching TV > or =10 hours/week, operating computer > or =45 hours/week, using copycat, microwave oven and mobile phone, electromagnetism equipment near the dwell or work place, e. g. switch room < or =50 m and launching tower < or =500 m in the cases are significantly higher than those in the controls in single factor analysis (all P < 0.05). After adjusted the effect of other risk factors by multifactor analysis, using microwave oven and mobile phone, contacting abnormal smell of fitment material > or =3 months, having emotional stress during the first term of pregnancy and spontaneous abortion history were significantly associated with risk of spontaneous abortion. The odds ratios of these risk factors were 2.23 and 4.63, respectively. Using microwave oven and mobile phone, contacting abnormal smell of fitment material > or =3 months, having emotional stress during the first term of pregnancy, and spontaneous abortion history are risk factors of early spontaneous abortion.

  9. Different responses of spontaneous and stimulus-related alpha activity to ambient luminance changes.

    PubMed

    Benedetto, Alessandro; Lozano-Soldevilla, Diego; VanRullen, Rufin

    2017-12-04

    Alpha oscillations are particularly important in determining our percepts and have been implicated in fundamental brain functions. Oscillatory activity can be spontaneous or stimulus-related. Furthermore, stimulus-related responses can be phase- or non-phase-locked to the stimulus. Non-phase-locked (induced) activity can be identified as the average amplitude changes in response to a stimulation, while phase-locked activity can be measured via reverse-correlation techniques (echo function). However, the mechanisms and the functional roles of these oscillations are far from clear. Here, we investigated the effect of ambient luminance changes, known to dramatically modulate neural oscillations, on spontaneous and stimulus-related alpha. We investigated the effect of ambient luminance on EEG alpha during spontaneous human brain activity at rest (experiment 1) and during visual stimulation (experiment 2). Results show that spontaneous alpha amplitude increased by decreasing ambient luminance, while alpha frequency remained unaffected. In the second experiment, we found that under low-luminance viewing, the stimulus-related alpha amplitude was lower, and its frequency was slightly faster. These effects were evident in the phase-locked part of the alpha response (echo function), but weaker or absent in the induced (non-phase-locked) alpha responses. Finally, we explored the possible behavioural correlates of these modulations in a monocular critical flicker frequency task (experiment 3), finding that dark adaptation in the left eye decreased the temporal threshold of the right eye. Overall, we found that ambient luminance changes impact differently on spontaneous and stimulus-related alpha expression. We suggest that stimulus-related alpha activity is crucial in determining human temporal segmentation abilities. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  10. Oscillatory brain activity in spontaneous and induced sleep stages in flies.

    PubMed

    Yap, Melvyn H W; Grabowska, Martyna J; Rohrscheib, Chelsie; Jeans, Rhiannon; Troup, Michael; Paulk, Angelique C; van Alphen, Bart; Shaw, Paul J; van Swinderen, Bruno

    2017-11-28

    Sleep is a dynamic process comprising multiple stages, each associated with distinct electrophysiological properties and potentially serving different functions. While these phenomena are well described in vertebrates, it is unclear if invertebrates have distinct sleep stages. We perform local field potential (LFP) recordings on flies spontaneously sleeping, and compare their brain activity to flies induced to sleep using either genetic activation of sleep-promoting circuitry or the GABA A agonist Gaboxadol. We find a transitional sleep stage associated with a 7-10 Hz oscillation in the central brain during spontaneous sleep. Oscillatory activity is also evident when we acutely activate sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila. In contrast, sleep following Gaboxadol exposure is characterized by low-amplitude LFPs, during which dFB-induced effects are suppressed. Sleep in flies thus appears to involve at least two distinct stages: increased oscillatory activity, particularly during sleep induction, followed by desynchronized or decreased brain activity.

  11. What are the origins and relevance of spontaneous bladder contractions? ICI-RS 2017.

    PubMed

    Drake, Marcus J; Fry, Christopher H; Hashitani, Hikaru; Kirschner-Hermanns, Ruth; Rahnama'i, Mohammad S; Speich, John E; Tomoe, Hikaru; Kanai, Anthony J; McCloskey, Karen D

    2018-01-23

    Storage phase bladder activity is a counter-intuitive observation of spontaneous contractions. They are potentially an intrinsic feature of the smooth muscle, but interstitial cells in the mucosa and the detrusor itself, as well as other muscular elements in the mucosa may substantially influence them. They are identified in several models explaining lower urinary tract dysfunction. A consensus meeting at the International Consultation on Incontinence Research Society (ICI-RS) 2017 congress considered the origins and relevance of spontaneous bladder contractions by debating which cell type(s) modulate bladder spontaneous activity, whether the methodologies are sufficiently robust, and implications for healthy and abnormal lower urinary tract function. The identified research priorities reflect a wide range of unknown aspects. Cellular contributions to spontaneous contractions in detrusor smooth muscle are still uncertain. Accordingly, insight into the cellular physiology of the bladder wall, particularly smooth muscle cells, interstitial cells, and urothelium, remains important. Upstream influences, such as innervation, endocrine, and paracrine factors, are particularly important. The cellular interactions represent the key understanding to derive the integrative physiology of organ function, notably the nature of signalling between mucosa and detrusor layers. Indeed, it is still not clear to what extent spontaneous contractions generated in isolated preparations mirror their normal and pathological counterparts in the intact bladder. Improved models of how spontaneous contractions influence pressure generation and sensory nerve function are also needed. Deriving approaches to robust evaluation of spontaneous contractions and their influences for experimental and clinical use could yield considerable progress in functional urology. © 2018 Wiley Periodicals, Inc.

  12. Altered spontaneous brain activity pattern in patients with late monocular blindness in middle-age using amplitude of low-frequency fluctuation: a resting-state functional MRI study

    PubMed Central

    Li, Qing; Huang, Xin; Ye, Lei; Wei, Rong; Zhang, Ying; Zhong, Yu-Lin; Jiang, Nan; Shao, Yi

    2016-01-01

    Objective Previous reports have demonstrated significant brain activity changes in bilateral blindness, whereas brain activity changes in late monocular blindness (MB) at rest are not well studied. Our study aimed to investigate spontaneous brain activity in patients with late middle-aged MB using the amplitude of low-frequency fluctuation (ALFF) method and their relationship with clinical features. Methods A total of 32 patients with MB (25 males and 7 females) and 32 healthy control (HC) subjects (25 males and 7 females), similar in age, sex, and education, were recruited for the study. All subjects were performed with resting-state functional magnetic resonance imaging scanning. The ALFF method was applied to evaluate spontaneous brain activity. The relationships between the ALFF signal values in different brain regions and clinical features in MB patients were investigated using correlation analysis. Results Compared with HCs, the MB patients had marked lower ALFF values in the left cerebellum anterior lobe, right parahippocampal gyrus, right cuneus, left precentral gyrus, and left paracentral lobule, but higher ALFF values in the right middle frontal gyrus, left middle frontal gyrus, and left supramarginal gyrus. However, there was no linear correlation between the mean ALFF signal values in brain regions and clinical manifestations in MB patients. Conclusion There were abnormal spontaneous activities in many brain regions including vision and vision-related regions, which might indicate the neuropathologic mechanisms of vision loss in the MB patients. Meanwhile, these brain activity changes might be used as a useful clinical indicator for MB. PMID:27980398

  13. Light/dark phase-dependent spontaneous activity is maintained in dopamine-deficient mice.

    PubMed

    Fujita, Masayo; Hagino, Yoko; Takeda, Taishi; Kasai, Shinya; Tanaka, Miho; Takamatsu, Yukio; Kobayashi, Kazuto; Ikeda, Kazutaka

    2017-10-16

    Dopamine is important for motor control and involved in the regulation of circadian rhythm. We previously found that dopamine-deficient (DD) mice became hyperactive in a novel environment 72 h after the last injection of L-3,4-dihydroxyphenylalanine (L-DOPA) when dopamine was almost completely depleted. DD mice did not initially exhibit hyperactivity in their home cages, but the animals exhibited hyperactivity several hours after the last L-DOPA injection. The regulation of motor activity in a novel environment and in home cages may be different. A previous study reported that DD mice became active again approximately 24 h after the last L-DOPA injection. One speculation was that light/dark phase-dependent spontaneous activity might be maintained despite dopamine deficiency. The present study investigated whether spontaneous home cage activity is maintained in DD mice 24-43 h and 72-91 h after the last L-DOPA injection. Spontaneous activity was almost completely suppressed during the light phase of the light/dark cycle in DD mice 24 and 72 h after the last L-DOPA injection. After the dark phase began, DD mice became active 24 and 72 h after the last L-DOPA injection. DD mice exhibited a similar amount of locomotor activity as wildtype mice 24 h after the last L-DOPA injection. Although DD mice presented a decrease in activity 72 h after the last L-DOPA injection, they maintained dark phase-stimulated locomotor activation. Despite low levels of dopamine in DD mice, they exhibited feeding behavior that was similar to wildtype mice. Although grooming and rearing behavior significantly decreased, DD mice retained their ability to perform these activities. Haloperidol treatment significantly suppressed all of these behaviors in wildtype mice but not in DD mice. These results indicate that DD mice maintain some aspects of light/dark phase-dependent spontaneous activity despite dopamine depletion, suggesting that compensatory dopamine-independent mechanisms might

  14. A gravimetric method for the measurement of total spontaneous activity in rats.

    PubMed

    Biesiadecki, B J; Brand, P H; Koch, L G; Britton, S L

    1999-10-01

    Currently available methods for the measurement of spontaneous activity of laboratory animals require expensive, specialized equipment and may not be suitable for use in low light conditions with nocturnal species. We developed a gravimetric method that uses common laboratory equipment to quantify the total spontaneous activity of rats and is suitable for use in the dark. The rat in its home cage is placed on a top-loading electronic balance interfaced to a computer. Movements are recorded by the balance as changes in weight and transmitted to the computer at 10 Hz. Data are analyzed on-line to derive the absolute value of the difference in weight between consecutive samples, and the one-second average of the absolute values is calculated. The averages are written to file for off-line analysis and summed over the desired observation period to provide a measure of total spontaneous activity. The results of in vitro experiments demonstrated that: 1) recorded weight changes were not influenced by position of the weight on the bottom of the cage, 2) values recorded from a series of weight changes were not significantly different from the calculated values, 3) the constantly decreasing force exerted by a swinging pendulum placed on the balance was accurately recorded, 4) the measurement of activity was not influenced by the evaporation of a fluid such as urine, and 5) the method can detect differences in the activity of sleeping and waking rats over a 10-min period, as well as during 4-hr intervals recorded during active (night-time) and inactive (daytime) periods. These results demonstrate that this method provides an inexpensive, accurate, and noninvasive method to quantitate the spontaneous activity of small animals.

  15. Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque

    PubMed Central

    Fukushima, Makoto; Saunders, Richard C.; Leopold, David A.; Mishkin, Mortimer; Averbeck, Bruno B.

    2012-01-01

    Summary In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here we used chronic micro-electrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. PMID:22681693

  16. Large-scale cortical correlation structure of spontaneous oscillatory activity

    PubMed Central

    Hipp, Joerg F.; Hawellek, David J.; Corbetta, Maurizio; Siegel, Markus; Engel, Andreas K.

    2013-01-01

    Little is known about the brain-wide correlation of electrophysiological signals. Here we show that spontaneous oscillatory neuronal activity exhibits frequency-specific spatial correlation structure in the human brain. We developed an analysis approach that discounts spurious correlation of signal power caused by the limited spatial resolution of electrophysiological measures. We applied this approach to source estimates of spontaneous neuronal activity reconstructed from magnetoencephalography (MEG). Overall, correlation of power across cortical regions was strongest in the alpha to beta frequency range (8–32 Hz) and correlation patterns depended on the underlying oscillation frequency. Global hubs resided in the medial temporal lobe in the theta frequency range (4–6 Hz), in lateral parietal areas in the alpha to beta frequency range (8–23 Hz), and in sensorimotor areas for higher frequencies (32–45 Hz). Our data suggest that interactions in various large-scale cortical networks may be reflected in frequency specific power-envelope correlations. PMID:22561454

  17. [Nonoperative management of spontaneous splenic rupture in infectious mononucleosis].

    PubMed

    Szczepanik, Andrzej B; Gajda, Sławomir; Szczepanik, Anna M; Misiak, Andrzej

    2011-04-01

    Spontaneous splenic rupture is a rare complication of infectious mononucleosis observed in 0.1-0.5% of patients with this condition. Mandatory mode of management in hemodynamically stable patients is nonoperative treatment. We report the case of a 19-year old man with splenic rupture, during the course of serological and hematological confirmed infectious mononucleosis, with no history of trauma. Parenchymal and subcapsular splenic hematomas and presence of blood in vesico-rectal recess was demonstrated. Circulatory and respiratory findings and blood cell count were stable. Nonoperative management was instituted which comprised monitoring of valid vital signs, serial USG and tomography scans and vital activity limitation. Imaging radiological investigations demonstrated disappearance of observed abnormalities on post admission day 20. The patient was discharged from the hospital in good general condition. Nonoperative management can be a safe alternative to splenectomy in hemodynamically stable patient with spontaneous rupture of the spleen.

  18. Reproduction of overall spontaneous pain pattern by manual stimulation of active myofascial trigger points in fibromyalgia patients

    PubMed Central

    2011-01-01

    Introduction It has previously been reported that local and referred pain from active myofascial trigger points (MTPs) in the neck and shoulder region contribute to fibromyalgia (FM) pain and that the pain pattern induced from active MTPs can reproduce parts of the spontaneous clinical FM pain pattern. The current study investigated whether the overall spontaneous FM pain pattern can be reproduced by local and referred pain from active MTPs located in different muscles. Methods A spontaneous pain pattern in FM was recorded in 30 FM patients and 30 healthy subjects served as controls. Local and referred pain patterns induced from active (patients) and latent (controls) MTPs were recorded following manual stimulation. The existence of MTPs was confirmed by intramuscular electromyographical registration of spontaneous electrical activity. Results Local and referred pain areas induced from key active MTPs in FM were larger than pain areas from latent MTPs in healthy controls (P < 0.001), but were similar to the overall spontaneous FM pain area in FM (P > 0.05). The induced pain area was positively associated with current spontaneous pain intensity in FM (P < 0.01). The locations of key active MTPs in FM patients were found to have latent MTPs in healthy subjects. The muscles containing key active MTPs in FM are often observed in the muscles of extensor digitorum, trapezius, infraspinatus in the upper part of the body and of quadratus lumborum, gluteus medius in the lower part of the body. Conclusions The overall spontaneous FM pain pattern can be reproduced by mechanical stimulation of active MTPs located in different muscles, suggesting that fibromyalgia pain is largely composed of pain arising from muscle pain and spasm. Targeting active MTPs and related perpetuating factors may be an important strategy in FM pain control. Trial registration ISRCTN ISRCTN43167547. PMID:21426569

  19. Spontaneous Reduction in Abnormal Myocardial Uptake of Fluorine-18 Fluorodeoxygluose in a Patient with Cardiac Sarcoidosis.

    PubMed

    Terasaki, Fumio; Fujita, Shu-Ichi; Kanzaki, Yumiko; Hirose, Yoshinobu; Ishizaka, Nobukazu

    2018-05-30

    Fluorine-18 fluorodeoxygluose ( 18 F-FDG) positron emission tomography (PET) is a useful tool for evaluating disease activity in sarcoidosis including cardiac involvement. A 67-year-old patient who developed atrioventricular block requiring permanent pacemaker implantation was diagnosed with cardiac sarcoidosis. The patient did not undergo steroid or immunosuppressive therapy but underwent serial 18 F-FDG PET examination, which showed spontaneous reduction in the myocardial FDG uptake, indicating the remission of immune-inflammatory activity. Although the global systolic function remained preserved, thinning of the septal wall emerged during the clinical course of follow-up, which is characteristic for cardiac sarcoidosis.

  20. Spontaneous high-gamma band activity reflects functional organization of auditory cortex in the awake macaque.

    PubMed

    Fukushima, Makoto; Saunders, Richard C; Leopold, David A; Mishkin, Mortimer; Averbeck, Bruno B

    2012-06-07

    In the absence of sensory stimuli, spontaneous activity in the brain has been shown to exhibit organization at multiple spatiotemporal scales. In the macaque auditory cortex, responses to acoustic stimuli are tonotopically organized within multiple, adjacent frequency maps aligned in a caudorostral direction on the supratemporal plane (STP) of the lateral sulcus. Here, we used chronic microelectrocorticography to investigate the correspondence between sensory maps and spontaneous neural fluctuations in the auditory cortex. We first mapped tonotopic organization across 96 electrodes spanning approximately two centimeters along the primary and higher auditory cortex. In separate sessions, we then observed that spontaneous activity at the same sites exhibited spatial covariation that reflected the tonotopic map of the STP. This observation demonstrates a close relationship between functional organization and spontaneous neural activity in the sensory cortex of the awake monkey. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Spontaneous default network activity reflects behavioral variability independent of mind-wandering.

    PubMed

    Kucyi, Aaron; Esterman, Michael; Riley, Clay S; Valera, Eve M

    2016-11-29

    The brain's default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain-behavior-experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report.

  2. Spontaneous default network activity reflects behavioral variability independent of mind-wandering

    PubMed Central

    Kucyi, Aaron; Esterman, Michael; Riley, Clay S.; Valera, Eve M.

    2016-01-01

    The brain’s default mode network (DMN) is highly active during wakeful rest when people are not overtly engaged with a sensory stimulus or externally oriented task. In multiple contexts, increased spontaneous DMN activity has been associated with self-reported episodes of mind-wandering, or thoughts that are unrelated to the present sensory environment. Mind-wandering characterizes much of waking life and is often associated with error-prone, variable behavior. However, increased spontaneous DMN activity has also been reliably associated with stable, rather than variable, behavior. We aimed to address this seeming contradiction and to test the hypothesis that single measures of attentional states, either based on self-report or on behavior, are alone insufficient to account for DMN activity fluctuations. Thus, we simultaneously measured varying levels of self-reported mind-wandering, behavioral variability, and brain activity with fMRI during a unique continuous performance task optimized for detecting attentional fluctuations. We found that even though mind-wandering co-occurred with increased behavioral variability, highest DMN signal levels were best explained by intense mind-wandering combined with stable behavior simultaneously, compared with considering either single factor alone. These brain–behavior–experience relationships were highly consistent within known DMN subsystems and across DMN subregions. In contrast, such relationships were absent or in the opposite direction for other attention-relevant networks (salience, dorsal attention, and frontoparietal control networks). Our results suggest that the cognitive processes that spontaneous DMN activity specifically reflects are only partially related to mind-wandering and include also attentional state fluctuations that are not captured by self-report. PMID:27856733

  3. [Cellular mechanism of the generation of spontaneous activity in gastric muscle].

    PubMed

    Nakamura, Eri; Kito, Yoshihiko; Fukuta, Hiroyasu; Yanai, Yoshimasa; Hashitani, Hikaru; Yamamoto, Yoshimichi; Suzuki, Hikaru

    2004-03-01

    In gastric smooth muscles, interstitial cells of Cajal (ICC) might be the pacemaker cells of spontaneous activities since ICC are rich in mitochondria and are connected with smooth muscle cells via gap junctions. Several types of ICC are distributed widely in the stomach wall. A group of ICC distributed in the myenteric layer (ICC-MY) were the pacemaker cells of gastrointestinal smooth muscles. Pacemaker potentials were generated in ICC-MY, and the potentials were conducted to circular smooth muscles to trigger slow waves and also conducted to longitudinal muscles to form follower potentials. In circular muscle preparations, interstitial cells distributed within muscle bundles (ICC-IM) produced unitary potentials, which were conducted to circular muscles to form slow potentials by summation. In mutant mice lacking inositol trisphosphate (IP(3)) receptor, slow waves were absent in gastric smooth muscles. The generation of spontaneous activity was impaired by the inhibition of Ca(2+)-release from internal stores through IP(3) receptors, inhibition of mitochondrial Ca(2+)-handling with proton pump inhibitors, and inhibition of ATP-sensitive K(+)-channels at the mitochondrial inner membrane. These results suggested that mitochondrial Ca(2+)-handling causes the generation of spontaneous activity in pacemaker cells. Possible involvement of protein kinase C (PKC) in the Ca(2+) signaling system was also suggested.

  4. Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

    PubMed

    Peinado, Alejandro; Abrams, Charles K

    2015-01-01

    Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying

  5. Endobronchial angiofibroma in the aberrant tracheal bronchus presenting as spontaneous pneumomediastinum.

    PubMed

    Kim, Kyung Soo; Moon, Young Kyu; Jeon, Hyun Woo; Park, Chan Beom; Ahn, Myeong Im; Lee, Kyo Young; Park, Jae Kil

    2015-07-22

    Spontaneous pneumomediastinum is a self-limiting benign disease but abnormal bronchial lesions can be rarely found incidentally, and in selected cases will require surgical resection. A 38-year-old man presented with a spontaneous pneumomediastinum. Chest computed tomography revealed an incidental linear endobronchial tumour in the aberrant tracheal bronchus. The tumour was removed surgically and diagnosed with a rare benign tumour of endobronchial angiofibroma. We report a rare case of endobronchial angiofibroma in the aberrant tracheal bronchus which was detected during the evaluation of a spontaneous pneumomediastinum.

  6. Visual experience sculpts whole-cortex spontaneous infraslow activity patterns through an Arc-dependent mechanism

    PubMed Central

    Kraft, Andrew W.; Mitra, Anish; Bauer, Adam Q.; Raichle, Marcus E.; Culver, Joseph P.; Lee, Jin-Moo

    2017-01-01

    Decades of work in experimental animals has established the importance of visual experience during critical periods for the development of normal sensory-evoked responses in the visual cortex. However, much less is known concerning the impact of early visual experience on the systems-level organization of spontaneous activity. Human resting-state fMRI has revealed that infraslow fluctuations in spontaneous activity are organized into stereotyped spatiotemporal patterns across the entire brain. Furthermore, the organization of spontaneous infraslow activity (ISA) is plastic in that it can be modulated by learning and experience, suggesting heightened sensitivity to change during critical periods. Here we used wide-field optical intrinsic signal imaging in mice to examine whole-cortex spontaneous ISA patterns. Using monocular or binocular visual deprivation, we examined the effects of critical period visual experience on the development of ISA correlation and latency patterns within and across cortical resting-state networks. Visual modification with monocular lid suturing reduced correlation between left and right cortices (homotopic correlation) within the visual network, but had little effect on internetwork correlation. In contrast, visual deprivation with binocular lid suturing resulted in increased visual homotopic correlation and increased anti-correlation between the visual network and several extravisual networks, suggesting cross-modal plasticity. These network-level changes were markedly attenuated in mice with genetic deletion of Arc, a gene known to be critical for activity-dependent synaptic plasticity. Taken together, our results suggest that critical period visual experience induces global changes in spontaneous ISA relationships, both within the visual network and across networks, through an Arc-dependent mechanism. PMID:29087327

  7. Spontaneous, synchronous electrical activity in neonatal mouse cortical neurones

    PubMed Central

    Corlew, Rebekah; Bosma, Martha M; Moody, William J

    2004-01-01

    Spontaneous [Ca2+]i transients were measured in the mouse neocortex from embryonic day 16 (E16) to postnatal day 6 (P6). On the day of birth (P0), cortical neurones generated widespread, highly synchronous [Ca2+]i transients over large areas. On average, 52% of neurones participated in these transients, and in 20% of slices, an average of 80% participated. These transients were blocked by TTX and nifedipine, indicating that they resulted from Ca2+ influx during electrical activity, and occurred at a mean frequency of 0.91 min−1. The occurrence of this activity was highly centred at P0: at E16 and P2 an average of only 15% and 24% of neurones, respectively, participated in synchronous transients, and they occurred at much lower frequencies at both E16 and P2 than at P0. The overall frequency of [Ca2+]i transients in individual cells did not change between E16 and P2, just the degree of their synchronicity. The onset of this spontaneous, synchronous activity correlated with a large increase in Na+ current density that occurred just before P0, and its cessation with a large decrease in resting resistance that occurred just after P2. This widespread, synchronous activity may serve a variety of functions in the neonatal nervous system. PMID:15297578

  8. Nitric oxide signaling pathways involved in the inhibition of spontaneous activity in the guinea pig prostate.

    PubMed

    Dey, Anupa; Lang, Richard J; Exintaris, Betty

    2012-06-01

    We investigated nitric oxide mediated inhibition of spontaneous activity recorded in young and aging guinea pig prostates. Conventional intracellular microelectrode and tension recording techniques were used. The nitric oxide donor sodium nitroprusside (10 μM) abolished spontaneous contractions and slow wave activity in 5 young and 5 aging prostates. Upon adding the nitric oxide synthase inhibitor L-NAME (10 μM) the frequency of spontaneous contractile and electrical activity was significantly increased in each age group. This increase was significantly larger in 4 to 8 preparations of younger vs aging prostates (about 40% to 50% vs about 10% to 20%, 2-way ANOVA p<0.01). Other measured parameters, including the duration, amplitude and membrane potential of spontaneous electrical and contractile activity, were not altered from control values. The guanylate cyclase inhibitor ODQ (10 μM) significantly increased the frequency of spontaneous activity by 10% to 30% in 6 young guinea pig prostates (Student paired t test p<0.05). However, it had no effect on aging prostates. The cGMP analogue 8-Br-GMP (1 μM) and the PDE5 inhibitor dipyridamole (1 μM) significantly decreased the frequency of contractile activity by about 70% in 4 to 9 young and older prostates (Student paired t test p<0.05). The decrease in the response to L-NAME in spontaneous contractile and slow wave activity in aging prostate tissue compared to that in young prostates suggests that with age there is a decrease in nitric oxide production. This may further explain the increase in prostatic smooth muscle tone observed in age related prostate specific conditions, such as benign prostatic hyperplasia. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Spontaneous activity in default-mode network predicts ascription of self-relatedness to stimuli.

    PubMed

    Qin, Pengmin; Grimm, Simone; Duncan, Niall W; Fan, Yan; Huang, Zirui; Lane, Timothy; Weng, Xuchu; Bajbouj, Malek; Northoff, Georg

    2016-04-01

    Spontaneous activity levels prior to stimulus presentation can determine how that stimulus will be perceived. It has also been proposed that such spontaneous activity, particularly in the default-mode network (DMN), is involved in self-related processing. We therefore hypothesised that pre-stimulus activity levels in the DMN predict whether a stimulus is judged as self-related or not. Participants were presented in the MRI scanner with a white noise stimulus that they were instructed contained their name or another. They then had to respond with which name they thought they heard. Regions where there was an activity level difference between self and other response trials 2 s prior to the stimulus being presented were identified. Pre-stimulus activity levels were higher in the right temporoparietal junction, the right temporal pole and the left superior temporal gyrus in trials where the participant responded that they heard their own name than trials where they responded that they heard another. Pre-stimulus spontaneous activity levels in particular brain regions, largely overlapping with the DMN, predict the subsequent judgement of stimuli as self-related. This extends our current knowledge of self-related processing and its apparent relationship with intrinsic brain activity in what can be termed a rest-self overlap. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  10. Dopamine Attenuates Ketamine-Induced Neuronal Apoptosis in the Developing Rat Retina Independent of Early Synchronized Spontaneous Network Activity.

    PubMed

    Dong, Jing; Gao, Lingqi; Han, Junde; Zhang, Junjie; Zheng, Jijian

    2017-07-01

    Deprivation of spontaneous rhythmic electrical activity in early development by anesthesia administration, among other interventions, induces neuronal apoptosis. However, it is unclear whether enhancement of neuronal electrical activity attenuates neuronal apoptosis in either normal development or after anesthesia exposure. The present study investigated the effects of dopamine, an enhancer of spontaneous rhythmic electrical activity, on ketamine-induced neuronal apoptosis in the developing rat retina. TUNEL and immunohistochemical assays indicated that ketamine time- and dose-dependently aggravated physiological and ketamine-induced apoptosis and inhibited early-synchronized spontaneous network activity. Dopamine administration reversed ketamine-induced neuronal apoptosis, but did not reverse the inhibitory effects of ketamine on early synchronized spontaneous network activity despite enhancing it in controls. Blockade of D1, D2, and A2A receptors and inhibition of cAMP/PKA signaling partially antagonized the protective effect of dopamine against ketamine-induced apoptosis. Together, these data indicate that dopamine attenuates ketamine-induced neuronal apoptosis in the developing rat retina by activating the D1, D2, and A2A receptors, and upregulating cAMP/PKA signaling, rather than through modulation of early synchronized spontaneous network activity.

  11. Relative Contributions of Specific Activity Histories and Spontaneous Processes to Size Remodeling of Glutamatergic Synapses

    PubMed Central

    Dvorkin, Roman; Ziv, Noam E.

    2016-01-01

    The idea that synaptic properties are defined by specific pre- and postsynaptic activity histories is one of the oldest and most influential tenets of contemporary neuroscience. Recent studies also indicate, however, that synaptic properties often change spontaneously, even in the absence of specific activity patterns or any activity whatsoever. What, then, are the relative contributions of activity history-dependent and activity history-independent processes to changes synapses undergo? To compare the relative contributions of these processes, we imaged, in spontaneously active networks of cortical neurons, glutamatergic synapses formed between the same axons and neurons or dendrites under the assumption that their similar activity histories should result in similar size changes over timescales of days. The size covariance of such commonly innervated (CI) synapses was then compared to that of synapses formed by different axons (non-CI synapses) that differed in their activity histories. We found that the size covariance of CI synapses was greater than that of non-CI synapses; yet overall size covariance of CI synapses was rather modest. Moreover, momentary and time-averaged sizes of CI synapses correlated rather poorly, in perfect agreement with published electron microscopy-based measurements of mouse cortex synapses. A conservative estimate suggested that ~40% of the observed size remodeling was attributable to specific activity histories, whereas ~10% and ~50% were attributable to cell-wide and spontaneous, synapse-autonomous processes, respectively. These findings demonstrate that histories of naturally occurring activity patterns can direct glutamatergic synapse remodeling but also suggest that the contributions of spontaneous, possibly stochastic, processes are at least as great. PMID:27776122

  12. Abnormal patterns of displacement activities: a review and reinterpretation.

    PubMed

    Anselme, Patrick

    2008-09-01

    A series of important theoretical contributions flourished in the years 1950-1970 about displacement activities -- those 'out-of-context' actions expressed by organisms in stressful situations. Nothing really new has appeared thereafter. Although the models address different issues, such as causal factors of displacement, it appears obvious that they do not provide a unified (coherent) approach; they often explain the same phenomena using very different means and turn out to be contradictory on several points. In addition, some problems currently remain unsolved, especially concerning the fact that displacement activities exhibit 'abnormalities' of expression in comparison with the same activities performed in usual context. Each model is here described and criticized in order to evaluate its explanatory power and allow the identification of specific limits. A new, integrative model -- the Anticipatory Dynamics Model (or ADM) -- then attempts to overcome the failures of previous models. The ADM suggests that abnormal patterns of displacement activities result from attentional interference caused by a thwarting experience or conflicting motivations. At least one theoretical prediction of the ADM can be differentiated from that of any other model.

  13. Chromosomal abnormalities as a cause of recurrent abortions in Egypt

    PubMed Central

    El-Dahtory, Faeza Abdel Mogib

    2011-01-01

    BACKGROUND: In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural. MATERIAL AND METHODS: Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University. RESULTS: We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical. CONCLUSION: Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion. PMID:22090718

  14. A morphologic study of unfertilized oocytes and abnormal embryos in human in vitro fertilization.

    PubMed

    Bałakier, H; Casper, R F

    1991-04-01

    The morphology of human, unfertilized oocytes and abnormal embryos cultured in vitro for 48-72 hr was examined in an attempt to learn more about oocyte maturation and reproductive failure in in vitro fertilization (IVF). About 21% of the unfertilized oocytes were totally degenerated. The majority (56%) of the remaining oocytes was arrested at the metaphase II stage. They contained coherent chromosomal plates and had extruded the first polar body with nuclear material. About 13% of oocytes underwent spontaneous activation. In most of these cases the second polar body was retained and many subnuclei or one big nucleus was formed. Five percent of metaphase II oocytes penetrated by sperm were not activated, likely as a result of oocyte immaturity. The developmental ability of abnormal embryos was poor. Several one-cell-stage zygotes were arrested at the pronuclear stage or at mitosis of the first mitotic division. Polyspermic embryos, especially those which contained four or more pronuclei, did not divide or formed uneven, multinucleated blastomeres. However, some triploid and tetraploid embryos often appeared normal morphologically despite their lethal chromosomal abnormalities.

  15. Modifications of spontaneous oculomotor activity in microgravitational conditions

    NASA Astrophysics Data System (ADS)

    Kornilova, L. N.; Goncharenko, A. M.; Polyakov, V. V.; Grigorova, V.; Manev, A.

    Investigations on spontaneous oculomotor activity were carried out prior to and after (five cosmonauts) and during space flight (two cosmonauts) on the 3rd, 5th and 164th days of the space flight. Recording of oculomotor activity was carried out by electrooculography on automated data acquisition and processing system "Zora" based on personal computers. During the space flight and after it all the cosmonauts with the eyes closed or open and dark-goggled showed an essential increase of the movements' amplitude when removing the eyes into the extreme positions especially in a vertical direction, occurrence of correcting saccadic movements (or nystagmus), an increase in time of fixing reactions.

  16. Time course of EEG background activity level before spontaneous awakening in infants.

    PubMed

    Zampi, Chiara; Fagioli, Igino; Salzarulo, Piero

    2002-12-01

    This research aimed to investigate the time course of the cortical activity level preceding spontaneous awakening as a function of age and state. Two groups of infants (1-4 and 9-14 weeks of age) were continuously monitored by polygraphic recording and behavioural observation during the night. The electroencephalographic (EEG) activity recorded by the C3-O1 lead was analysed through an automatic analysis method which provides, for each 30-s epoch, a single measure, time domain based, of the EEG synchronization. The EEG parameter values were computed in the 6 min preceding each awakening out of non-rapid eye movement (NREM) sleep and out of rapid eye movement (REM) sleep. The EEG background activity level did not change in the minutes preceding awakening out of REM sleep. Awakening out of NREM sleep was preceded by a change of EEG activity level in the direction of higher activation with different time course according to the age. Both REM and NREM sleep results suggest that a high level of EEG activity is a prerequisite for the occurrence of a spontaneous awakening.

  17. Congenital abnormalities of the inferior vena cava presenting clinically in adolescent males.

    PubMed

    Halparin, Jessica; Monagle, Paul; Newall, Fiona

    2015-04-01

    Congenital anatomic abnormality of the inferior vena cava (IVC) is an important risk factor for the development of spontaneous proximal lower extremity deep vein thrombosis (DVT) in young adults. The incidence of DVT associated with congenital IVC anomalies in paediatric populations has not been described, and the implications of IVC anomalies for treatment and outcomes of DVT are unknown. This study reports a series of five adolescent males with spontaneous lower extremity DVTs and underlying congenital IVC abnormalities. Cases were identified by searching the institutional database of patients treated with anticoagulation for venous thromboembolism at a tertiary children's hospital. The demographics, clinical presentations, imaging findings, treatment courses, and outcomes are described. All cases occurred in males, and accounted for approximately twenty percent of adolescent males presenting with DVT. IVC abnormality is likely an under-recognized risk factor for DVT in this age group, and detailed vascular imaging should be pursued in adolescents with spontaneous proximal lower extremity DVT when initial ultrasonography does not delineate the proximal clot extent. Management requires individual risk-benefit assessment in the context of providing developmentally appropriate care. Further research is required to establish long-term outcomes and determine optimal treatment strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Spontaneous activity of cochlear hair cells triggered by fluid secretion mechanism in adjacent support cells

    PubMed Central

    Wang, Han Chin; Lin, Chun-Chieh; Cheung, Rocky; Zhang-Hooks, YingXin; Agarwal, Amit; Ellis-Davies, Graham; Rock, Jason; Bergles, Dwight E.

    2015-01-01

    Summary Spontaneous electrical activity of neurons in developing sensory systems promotes their maturation and proper connectivity. In the auditory system, spontaneous activity of cochlear inner hair cells (IHCs) is initiated by the release of ATP from glia-like inner supporting cells (ISCs), facilitating maturation of central pathways before hearing onset. Here, we find that ATP stimulates purinergic autoreceptors in ISCs, triggering Cl− efflux and osmotic cell shrinkage by opening TMEM16A Ca2+-activated Cl− channels. Release of Cl− from ISCs also forces K+ efflux, causing transient depolarization of IHCs near ATP release sites. Genetic deletion of TMEM16A markedly reduces the spontaneous activity of IHCs and spiral ganglion neurons in the developing cochlea, and prevents ATP-dependent shrinkage of supporting cells. These results indicate that support cells in the developing cochlea have adapted a pathway used for fluid secretion in other organs to induce periodic excitation of hair cells. PMID:26627734

  19. Abnormal Neural Activation to Faces in the Parents of Children with Autism

    PubMed Central

    Yucel, G. H.; Belger, A.; Bizzell, J.; Parlier, M.; Adolphs, R.; Piven, J.

    2015-01-01

    Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the “Broad Autism Phenotype ” (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality (“BAP+”). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

  20. Abnormalities of thalamic activation and cognition in schizophrenia.

    PubMed

    Andrews, Jessica; Wang, Lei; Csernansky, John G; Gado, Mokhtar H; Barch, Deanna M

    2006-03-01

    Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.

  1. An update in recurrent spontaneous abortion.

    PubMed

    Pandey, Manoj Kumar; Rani, Reena; Agrawal, Suraksha

    2005-07-01

    Recurrent spontaneous abortion (RSA) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The etiology of recurrent spontaneous abortion is often unclear and may be multifactorial, with much controversy regarding diagnosis and treatment. Reasonably accepted etiologic causes include, genetics, anatomical, endocrine, placental anomalies, hormonal problems, infection, smoking and alcohol consumption, exposure to environmental factors, psychological trauma and stressful life event, certain coagulation and immunoregulatory protein defects. Detection of an abnormality in any of these areas may result into specific therapeutic measures, with varying degrees of success. However, the majority of cases of RSA remains unexplained and is found to be associated with certain autoimmune (APA, ANA, ACA, ATA, AECA) and alloimmune (APCA, Ab2, MLR-Bf) antibodies that may play major role in the immunologic failure of pregnancy and may lead to abortion. Alteration in the expression of HLA-G molecules, T-helper-1 (Th-1) pattern of cytokines and natural killer (NK) cells activity may also induce abortion. Various forms of treatment like antithrombotic therapies such as aspirin and heparin, intravenous immunoglobulin (IVIg) therapy, immunotherapy with paternal lymphocytes and vitamin D3 therapy are effective mode of treatment for unexplained cause of fetal loss in women with RSA.

  2. Effects of imatinib mesylate on the spontaneous activity generated by the guinea-pig prostate.

    PubMed

    Lam, Michelle; Dey, Anupa; Lang, Richard J; Exintaris, Betty

    2013-08-01

    What's known on the subject? and what does the study add?: Several studies have examined the functional role of tyrosine kinase receptors in the generation of spontaneous activity in various segments of the gastrointestinal and urogenital tracts through the application of its inhibitor, imatinib mesylate (Glivec®), but results are fairly inconsistent. This is the first study detailing the effects of imatinib mesylate on the spontaneous activity in the young and ageing prostate gland. As spontaneous electrical activity underlies the spontaneous rhythmic prostatic contractions that occur at rest, elucidating the mechanisms involved in the regulation of the spontaneous electrical activity and the resultant phasic contractions could conceivably lead to the identification of better targets and the development of more specific therapeutic agents to treat prostate conditions. To investigate the effect of imatinib mesylate, a tyrosine kinase receptor inhibitor, in the generation of spontaneous electrical and contractile activity in the young and ageing guinea-pig prostate. Standard tension and intracellular recording were used to measure spontaneous contractions and slow waves, respectively from the guinea-pig prostate at varying concentrations of imatinib mesylate (1-50 μm). Imatinib mesylate (1-10 μm), did not significantly affect slow waves recorded in the prostate of both age groups but at 50 μm, the amplitude of slow waves from the ageing guinea-pig prostate was significantly reduced (P < 0.05, n = 5). In contrast, the amplitude of contractions across all concentrations in the young guinea-pig prostate was reduced to between 35% and 41% of control, while the frequency was reduced to 15.7% at 1 μm (n = 7), 49.8% at 5 μm (n = 10), 46.2% at 10 μm (n = 7) and 53.1% at 50 μm (n = 5). Similarly, imatinib mesylate attenuated the amplitude and slowed the frequency of contractions in ageing guinea-pigs to 5.15% and 3.3% at 1 μm (n = 6); 21.1% and 20.8% at 5 μm (n = 8

  3. Neuroelectrical Decomposition of Spontaneous Brain Activity Measured with Functional Magnetic Resonance Imaging

    PubMed Central

    Liu, Zhongming; de Zwart, Jacco A.; Chang, Catie; Duan, Qi; van Gelderen, Peter; Duyn, Jeff H.

    2014-01-01

    Spontaneous activity in the human brain occurs in complex spatiotemporal patterns that may reflect functionally specialized neural networks. Here, we propose a subspace analysis method to elucidate large-scale networks by the joint analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data. The new approach is based on the notion that the neuroelectrical activity underlying the fMRI signal may have EEG spectral features that report on regional neuronal dynamics and interregional interactions. Applying this approach to resting healthy adults, we indeed found characteristic spectral signatures in the EEG correlates of spontaneous fMRI signals at individual brain regions as well as the temporal synchronization among widely distributed regions. These spectral signatures not only allowed us to parcel the brain into clusters that resembled the brain's established functional subdivision, but also offered important clues for disentangling the involvement of individual regions in fMRI network activity. PMID:23796947

  4. Central command differentially affects aortic and carotid sinus baroreflexes at the onset of spontaneous motor activity.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Idesako, Mitsuhiro; Ishida, Tomoko; Endo, Kana; Liang, Nan

    2013-12-01

    Our laboratory has recently demonstrated that central command provides selective inhibition of the cardiomotor component of aortic (AOR) baroreflex during exercise, preserving carotid sinus (CS) baroreflex. To further explore the differential effects of central command on the arterial baroreflexes, we surgically separated the AOR and CS baroreflex systems, to identify the input-output relationship of each baroreflex system using brief occlusion of the abdominal aorta in decerebrate cats. Baroreflex sensitivity for heart rate (HR) was estimated from the baroreflex ratio between the pressor and bradycardia responses during aortic occlusion and from the slope of the baroreflex curve between the changes in mean arterial blood pressure (ΔMAP) and ΔHR. Spontaneous motor activity accompanied the abrupt increases in HR and MAP. When aortic occlusion was given at the onset of spontaneous motor activity, the baroreflex ratio was blunted to 11-25% of the preexercise value in either intact or AOR baroreflex. The slope of the ΔMAP-ΔHR curve was similarly attenuated at the onset of spontaneous motor activity to 11-18% of the slope during the preexercise period. In contrast, in the CS baroreflex, the baroreflex ratio and curve slope were not significantly (P>0.05) altered by spontaneous motor activity. An upward shift of the baroreflex curve appeared at the onset of spontaneous motor activity, irrespective of the intact, AOR, and CS baroreflex conditions. Taken together, it is concluded that central command provides selective inhibition for the cardiomotor limb of the aortic baroreflex at the onset of exercise, which in turn contributes to an instantaneous increase in HR. © 2013.

  5. Prolonged exposure to a low-dose of bisphenol A increases spontaneous motor activity in adult male rats.

    PubMed

    Nojima, Kazuo; Takata, Tomoyo; Masuno, Hiroshi

    2013-07-01

    We investigated the effects of bisphenol A (BPA), an environmental endocrine-disrupting chemical, on spontaneous motor activity in adult male rats. The rats were implanted intraperitoneally with mini-osmotic pumps containing either BPA (50 μg/kg body weight per day) in sesame oil (BPA-treated group) or sesame oil only (vehicle-treated group). Spontaneous motor activity during a 24-h period was measured over 5 days from day 9 to day 13 after implantation using an animal movement analysis system. Spontaneous motor activity during the last 2 h of the dark phase and during the first 1-h of the light phase was increased in the BPA-treated group. Total spontaneous motor activity during the 12-h light phase, but not the 12-h dark phase, was higher in the BPA-treated group than in the vehicle-treated group. These findings suggest that BPA may induce hyperactivity in adult male rats during the 12-h light phase, especially during the 2 h immediately preceding sleep-onset and 1 h immediately following sleep-onset.

  6. Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.

    PubMed

    Berkes, Pietro; Orbán, Gergo; Lengyel, Máté; Fiser, József

    2011-01-07

    The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.

  7. Abnormal Neural Activation to Faces in the Parents of Children with Autism.

    PubMed

    Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

    2015-12-01

    Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Differential Modulation of Spontaneous and Evoked Thalamocortical Network Activity by Acetylcholine Level In Vitro

    PubMed Central

    Wester, Jason C.

    2013-01-01

    Different levels of cholinergic neuromodulatory tone have been hypothesized to set the state of cortical circuits either to one dominated by local cortical recurrent activity (low ACh) or to one dependent on thalamic input (high ACh). High ACh levels depress intracortical but facilitate thalamocortical synapses, whereas low levels potentiate intracortical synapses. Furthermore, recent work has implicated the thalamus in controlling cortical network state during waking and attention, when ACh levels are highest. To test this hypothesis, we used rat thalamocortical slices maintained in medium to generate spontaneous up- and down-states and applied different ACh concentrations to slices in which thalamocortical connections were either maintained or severed. The effects on spontaneous and evoked up-states were measured using voltage-sensitive dye imaging, intracellular recordings, local field potentials, and single/multiunit activity. We found that high ACh can increase the frequency of spontaneous up-states, but reduces their duration in slices with intact thalamocortical connections. Strikingly, when thalamic connections are severed, high ACh instead greatly reduces or abolishes spontaneous up-states. Furthermore, high ACh reduces the spatial propagation, velocity, and depolarization amplitude of evoked up-states. In contrast, low ACh dramatically increases up-state frequency regardless of the presence or absence of intact thalamocortical connections and does not reduce the duration, spatial propagation, or velocity of evoked up-states. Therefore, our data support the hypothesis that strong cholinergic modulation increases the influence, and thus the signal-to-noise ratio, of afferent input over local cortical activity and that lower cholinergic tone enhances recurrent cortical activity regardless of thalamic input. PMID:24198382

  9. Modulation of synaptic transmission from segmental afferents by spontaneous activity of dorsal horn spinal neurones in the cat.

    PubMed

    Manjarrez, E; Rojas-Piloni, J G; Jimenez, I; Rudomin, P

    2000-12-01

    We examined, in the anaesthetised cat, the influence of the neuronal ensembles producing spontaneous negative cord dorsum potentials (nCDPs) on segmental pathways mediating primary afferent depolarisation (PAD) of cutaneous and group I muscle afferents and on Ia monosynaptic activation of spinal motoneurones. The intraspinal distribution of the field potentials associated with the spontaneous nCDPs indicated that the neuronal ensembles involved in the generation of these potentials were located in the dorsal horn of lumbar segments, in the same region of termination of low-threshold cutaneous afferents. During the occurrence of spontaneous nCDPs, transmission from low-threshold cutaneous afferents to second order neurones in laminae III-VI, as well as transmission along pathways mediating PAD of cutaneous and Ib afferents, was facilitated. PAD of Ia afferents was instead inhibited. Monosynaptic reflexes of flexors and extensors were facilitated during the spontaneous nCDPs. The magnitude of the facilitation was proportional to the amplitude of the 'conditioning' spontaneous nCDPs. This led to a high positive correlation between amplitude fluctuations of spontaneous nCDPs and fluctuations of monosynaptic reflexes. Stimulation of low-threshold cutaneous afferents transiently reduced the probability of occurrence of spontaneous nCDPs as well as the fluctuations of monosynaptic reflexes. It is concluded that the spontaneous nCDPs were produced by the activation of a population of dorsal horn neurones that shared the same functional pathways and involved the same set of neurones as those responding monosynaptically to stimulation of large cutaneous afferents. The spontaneous activity of these neurones was probably the main cause of the fluctuations of the monosynaptic reflexes observed under anaesthesia and could provide a dynamic linkage between segmental sensory and motor pathways.

  10. Central command does not suppress baroreflex control of cardiac sympathetic nerve activity at the onset of spontaneous motor activity in the decerebrate cat.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Asahara, Ryota; Idesako, Mitsuhiro

    2016-10-01

    Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in animals. We have examined whether baroreflex control of cardiac sympathetic nerve activity (CSNA) and/or cardiovagal baroreflex sensitivity are altered at the onset of spontaneously occurring motor behavior, which was monitored with tibial nerve activity in paralyzed, decerebrate cats. CSNA exhibited a peak increase (126 ± 17%) immediately after exercise onset, followed by increases in HR and mean arterial pressure (MAP). With development of the pressor response, CSNA and HR decreased near baseline, although spontaneous motor activity was not terminated. Atropine methyl nitrate (0.1-0.2 mg/kg iv) with little central influence delayed the initial increase in HR but did not alter the response magnitudes of HR and CSNA, while atropine augmented the pressor response. The baroreflex-induced decreases in CSNA and HR elicited by brief occlusion of the abdominal aorta were challenged at the onset of spontaneous motor activity. Spontaneous motor activity blunted the baroreflex reduction in HR by aortic occlusion but did not alter the baroreflex inhibition of CSNA. Similarly, atropine abolished the baroreflex reduction in HR but did not influence the baroreflex inhibition of CSNA. Thus it is likely that central command increases CSNA and decreases cardiac vagal outflow at the onset of spontaneous motor activity while preserving baroreflex control of CSNA. Accordingly, central command must attenuate cardiovagal baroreflex sensitivity against an excess rise in MAP as estimated from the effect of muscarinic blockade. Copyright © 2016 the American Physiological Society.

  11. Lymphocytes from wasted mice express enhanced spontaneous and {gamma}-ray-induced apoptosis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woloschak, G.E.; Chang-Liu, Chin-Mei; Chung, Jen

    1993-09-01

    Mice bearing the autosomal recessive mutation wasted (wst/wst) display a disease pattern including faulty repair of DNA damage in lymphocytes after radiation exposure, neurologic abnormalities, and immunodeficiency. Many of the features of this mouse model have suggested a premature or increased spontaneous frequency of apoptosis in thymocytes; past work has shown an inability to establish cultured T cell lines, an abnormally high death rate of stimulated T cells in culture, and an increased sensitivity of T cells to the killing effects of ionizing radiations in wst/wst mice relative to controls. The experiments reported here were designed to examine splenic andmore » thymic lymphocytes from wasted and control mice for signs of early apoptosis. Our results revealed enhanced expression of Rp-8 mRNA (associated with apoptosis) in thymic lymphocytes and reduced expression in splenic lymphocytes of wst/wst mice relative to controls; expression of Rp-2 and Td-30 mRNA (induced during apoptosis) were not detectable in spleen or thymus. Higher spontaneous DNA fragmentation was observed in wasted mice than in controls; however, {gamma}-ray-induced DNA fragmentation peaked at a lower dose and occurred to a greater extent in wasted mice relative to controls. These results provide evidence for high spontaneous and {gamma}-ray-induced apoptosis in T cells of wasted mice as a mechanism underlying the observed lymphocyte and DNA repair abnormalities.« less

  12. A novel framework for intelligent surveillance system based on abnormal human activity detection in academic environments.

    PubMed

    Al-Nawashi, Malek; Al-Hazaimeh, Obaida M; Saraee, Mohamad

    2017-01-01

    Abnormal activity detection plays a crucial role in surveillance applications, and a surveillance system that can perform robustly in an academic environment has become an urgent need. In this paper, we propose a novel framework for an automatic real-time video-based surveillance system which can simultaneously perform the tracking, semantic scene learning, and abnormality detection in an academic environment. To develop our system, we have divided the work into three phases: preprocessing phase, abnormal human activity detection phase, and content-based image retrieval phase. For motion object detection, we used the temporal-differencing algorithm and then located the motions region using the Gaussian function. Furthermore, the shape model based on OMEGA equation was used as a filter for the detected objects (i.e., human and non-human). For object activities analysis, we evaluated and analyzed the human activities of the detected objects. We classified the human activities into two groups: normal activities and abnormal activities based on the support vector machine. The machine then provides an automatic warning in case of abnormal human activities. It also embeds a method to retrieve the detected object from the database for object recognition and identification using content-based image retrieval. Finally, a software-based simulation using MATLAB was performed and the results of the conducted experiments showed an excellent surveillance system that can simultaneously perform the tracking, semantic scene learning, and abnormality detection in an academic environment with no human intervention.

  13. Effects of imatinib mesylate on spontaneous electrical and mechanical activity in smooth muscle of the guinea-pig stomach

    PubMed Central

    Hashitani, H; Hayase, M; Suzuki, H

    2008-01-01

    Background and purpose: Effects of imatinib mesylate, a Kit receptor tyrosine kinase inhibitor, on spontaneous activity of interstitial cells of Cajal (ICC) and smooth muscles in the stomach were investigated. Experimental approach: Effects of imatinib on spontaneous electrical and mechanical activity were investigated by measuring changes in the membrane potential and tension recorded from smooth muscles of the guinea-pig stomach. Its effects on spontaneous changes in intracellular concentration of Ca2+ ([Ca2+]i) (Ca2+ transients) were also examined in fura-2-loaded preparations. Key results: Imatinib (1–10 μM) suppressed spontaneous contractions and Ca2+ transients. Simultaneous recordings of electrical and mechanical activity demonstrated that imatinib (1 μM) reduced the amplitude of spontaneous contractions without suppressing corresponding slow waves. In the presence of nifedipine (1 μM), imatinib (10 μM) reduced the duration of slow waves and follower potentials in the antrum and accelerated their generation, but had little affect on their amplitude. In contrast, imatinib reduced the amplitude of antral slow potentials and slow waves in the corpus. Conclusions and implications: Imatinib may suppress spontaneous contractions of gastric smooth muscles by inhibiting pathways that increase [Ca2+]i in smooth muscles rather than by specifically inhibiting the activity of ICC. A high concentration of imatinib (10 μM) reduced the duration of slow waves or follower potentials in the antrum, which reflect activity of ICC distributed in the myenteric layers (ICC-MY), and suppressed antral slow potentials or corporal slow waves, which reflect activity of ICC within the muscle bundles (ICC-IM), presumably by inhibiting intracellular Ca2+ handling. PMID:18414381

  14. Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland

    PubMed Central

    Dey, Anupa; Kusljic, Snezana; Lang, Richard J; Exintaris, Betty

    2010-01-01

    BACKGROUND AND PURPOSE To investigate the role of connexin 43 in the maintenance of spontaneous activity in prostate tissue from young and old guinea pigs. EXPERIMENTAL APPROACH Conventional intracellular microelectrode and tension recording techniques, coupled with Western blot analysis and immunohistochemistry for connexin 43 (CX43) were used. The effects of three gap junction uncouplers, 18β glycyrrhetinic acid (10 µM, 40 µM), carbenoxolone (10 µM, 50 µM) and octanol (0.5 mM, 1 mM), were studied in cells displaying slow wave activity and on spontaneously contracting tissue from prostate glands of young (2–5 months) and old (9–16 months) guinea pigs. KEY RESULTS 18β Glycyrrhetinic acid (40 µM), carbenoxolone (50 µM) or octanol (0.5 mM) abolished slow wave activity in prostate tissue from young and old guinea pigs and depolarized membrane potential by approximately 5 mV. These treatments also abolished all contractions in both sets of prostate tissue. These effects were reversed upon washout. Western blot analysis and CX43 immunohistochemistry showed that there was no age-related difference in the expression and distribution of CX43 in prostate tissues. CONCLUSION AND IMPLICATIONS When gap junctional communication via CX43 was disrupted, spontaneous activity was abolished at a cellular and whole tissue level; CX43 is therefore essential for the maintenance of spontaneous slow wave activity and subsequent contractile activity in the guinea pig prostate gland. PMID:20735413

  15. Where’s the Noise? Key Features of Spontaneous Activity and Neural Variability Arise through Learning in a Deterministic Network

    PubMed Central

    Hartmann, Christoph; Lazar, Andreea; Nessler, Bernhard; Triesch, Jochen

    2015-01-01

    Even in the absence of sensory stimulation the brain is spontaneously active. This background “noise” seems to be the dominant cause of the notoriously high trial-to-trial variability of neural recordings. Recent experimental observations have extended our knowledge of trial-to-trial variability and spontaneous activity in several directions: 1. Trial-to-trial variability systematically decreases following the onset of a sensory stimulus or the start of a motor act. 2. Spontaneous activity states in sensory cortex outline the region of evoked sensory responses. 3. Across development, spontaneous activity aligns itself with typical evoked activity patterns. 4. The spontaneous brain activity prior to the presentation of an ambiguous stimulus predicts how the stimulus will be interpreted. At present it is unclear how these observations relate to each other and how they arise in cortical circuits. Here we demonstrate that all of these phenomena can be accounted for by a deterministic self-organizing recurrent neural network model (SORN), which learns a predictive model of its sensory environment. The SORN comprises recurrently coupled populations of excitatory and inhibitory threshold units and learns via a combination of spike-timing dependent plasticity (STDP) and homeostatic plasticity mechanisms. Similar to balanced network architectures, units in the network show irregular activity and variable responses to inputs. Additionally, however, the SORN exhibits sequence learning abilities matching recent findings from visual cortex and the network’s spontaneous activity reproduces the experimental findings mentioned above. Intriguingly, the network’s behaviour is reminiscent of sampling-based probabilistic inference, suggesting that correlates of sampling-based inference can develop from the interaction of STDP and homeostasis in deterministic networks. We conclude that key observations on spontaneous brain activity and the variability of neural responses can be

  16. Introduction of a method for quantitative evaluation of spontaneous motor activity development with age in infants.

    PubMed

    Disselhorst-Klug, Catherine; Heinze, Franziska; Breitbach-Faller, Nico; Schmitz-Rode, Thomas; Rau, Günter

    2012-04-01

    Coordination between perception and action is required to interact with the environment successfully. This is already trained by very young infants who perform spontaneous movements to learn how their body interacts with the environment. The strategies used by the infants for this purpose change with age. Therefore, very early progresses in action control made by the infants can be investigated by monitoring the development of spontaneous motor activity. In this paper, an objective method is introduced, which allows the quantitative evaluation of the development of spontaneous motor activity in newborns. The introduced methodology is based on the acquisition of spontaneous movement trajectories of the feet by 3D movement analysis and subsequent calculation of specific movement parameters from them. With these movement-based parameters, it was possible to provide an objective description of age-dependent developmental steps in healthy newborns younger than 6 months. Furthermore, it has been shown that pathologies like infantile cerebral palsy influence development of motor activity significantly. Since the introduced methodology is objective and quantitative, it is suitable to monitor how newborns train their cognitive processes, which will enable them to cope with their environment by motor interaction.

  17. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  18. Regional homogeneity of spontaneous brain activity in adult patients with obsessive-compulsive disorder before and after cognitive behavioural therapy.

    PubMed

    Yang, Xiang-Yun; Sun, Jing; Luo, Jia; Zhong, Zhao-Xi; Li, Ping; Yao, Shu-Min; Xiong, Hong-Fang; Huang, Fang-Fang; Li, Zhan-Jiang

    2015-12-01

    Cognitive behavioural therapy (CBT) is an effective treatment for obsessive-compulsive disorder (OCD). Several neuroimaging studies have explored alterations of brain function in OCD patients as they performed tasks after CBT. However, the effects of CBT on the neural activityin OCD during rest remain unknown. Therefore, we investigated changes in regional homogeneity (ReHo) in OCD patients before and after CBT. Twenty-two OCD patients and 22 well-matched healthy controls participated in the resting-state functional magnetic resonance imaging scans. We compared differences in ReHo between the OCD and control groups before treatment and investigated the changes of ReHo in 17 OCD patients who responded to CBT. Compared to healthy controls, OCD patients exhibited higher ReHo in the right orbitofrontal cortex (OFC), bilateral middle frontal cortex, right precuneus, left cerebellum, and vermis, as well as lower ReHo in the bilateral caudate, right calcarine, right posterior cingulate cortex, and right middle temporal cortex. Along with the clinical improvement in OCD patients after CBT, we found decreased ReHo in the right OFC, bilateral middle frontal cortex, left cerebellum and vermis, and increased ReHo in the left caudate. Improvement of OCD symptoms was significantly correlated with the changed ReHo in the right OFC and left cerebellum. Although these findings are preliminary and need to be replicated in larger samples, they indicate the presence of abnormal spontaneous brain activity of the prefrontal-striatal-cerebellar circuit in OCD patients, and provide evidence that CBT can selectively modulate the spontaneous brain activity of this circuit in OCD patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Spontaneous brain activity predicts learning ability of foreign sounds.

    PubMed

    Ventura-Campos, Noelia; Sanjuán, Ana; González, Julio; Palomar-García, María-Ángeles; Rodríguez-Pujadas, Aina; Sebastián-Gallés, Núria; Deco, Gustavo; Ávila, César

    2013-05-29

    Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental-retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined.

  20. Localization of spontaneous magnetoencephalographic activity of neonates and fetuses using independent component and Hilbert phase analysis.

    PubMed

    Vairavan, Srinivasan; Eswaran, Hari; Preissl, Hubert; Wilson, James D; Haddad, Naim; Lowery, Curtis L; Govindan, Rathinaswamy B

    2010-01-01

    The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values.

  1. Bidirectional global spontaneous network activity precedes the canonical unidirectional circuit organization in the developing hippocampus.

    PubMed

    Shi, Yulin; Ikrar, Taruna; Olivas, Nicholas D; Xu, Xiangmin

    2014-06-15

    Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  2. fMRI amygdala activation during a spontaneous panic attack in a patient with panic disorder.

    PubMed

    Pfleiderer, Bettina; Zinkirciran, Sariye; Arolt, Volker; Heindel, Walter; Deckert, Juergen; Domschke, Katharina

    2007-01-01

    Previous studies on neuronal activation correlates of panic attacks were mostly based on challenge tests, sensory-related stimulation or fear conditioning in healthy subjects. In the present study, we report on a female patient with panic disorder experiencing a spontaneous panic attack under an auditory habituation paradigm in the last stimulation block with sine tones captured with fMRI at 3T. The panic attack was associated with a significantly increased activity in the right amygdala. This is the first report on neuronal activation correlates of a spontaneous panic attack in a patient with panic disorder as measured by fMRI, which lends further support to a pivotal role of the amygdala in the pathogenesis of the disease.

  3. Outcomes of Nulliparous Women with Spontaneous Labor Onset Admitted to Hospitals in Pre-active versus Active Labor

    PubMed Central

    NEAL, Jeremy L.; LAMP, Jane M.; BUCK, Jacalyn S.; LOWE, Nancy K.; GILLESPIE, Shannon L.; RYAN, Sharon L.

    2014-01-01

    Introduction The timing of when a woman is admitted to the hospital for labor care following spontaneous contraction onset may be among the most important decisions that labor attendants make as it can influence care patterns and birth outcomes. The aims of this study were to estimate the percentage of low-risk, nulliparous women at term who are admitted to labor units prior to active labor and to evaluate the effects of the timing of admission (i.e., pre-active versus active labor) on labor interventions and mode of birth. Methods Obstetrics data from low-risk, nulliparous women with spontaneous labor onset at term gestation (N = 216) were merged from two prospective studies conducted at three large, Midwestern hospitals. Baseline characteristics, labor interventions, and outcomes were compared between groups using Fisher’s exact and Mann-Whitney U tests, as appropriate. Likelihoods for oxytocin augmentation, amniotomy, and cesarean delivery were assessed by logistic regression. Results Of the sample of 216 low-risk nulliparous women, 114 (52.8%) were admitted in pre-active labor and 102 (47.2%) were admitted in active labor. Women admitted in pre-active labor were more likely to undergo oxytocin augmentation (84.2% and 45.1%, respectively; odds ratio (OR) 6.5, 95% confidence interval (CI) 3.43–12.27) but not amniotomy (55.3% and 61.8%, respectively; OR 0.8, 95% CI 0.44–1.32) when compared to women admitted in active labor. The likelihood of cesarean delivery was higher for women admitted before active labor onset (15.8% and 6.9%, respectively; OR 2.6, 95% CI 1.02–6.37). Discussion Many low-risk nulliparous women with regular, spontaneous uterine contractions are admitted to labor units before active labor onset, which increases their likelihood of receiving oxytocin and being delivered via cesarean section. An evidence-based, standardized approach for labor admission decision-making is recommended to decrease inadvertent admissions of women in pre-active

  4. Levetiracetam reduces abnormal network activations in temporal lobe epilepsy.

    PubMed

    Wandschneider, Britta; Stretton, Jason; Sidhu, Meneka; Centeno, Maria; Kozák, Lajos R; Symms, Mark; Thompson, Pamela J; Duncan, John S; Koepp, Matthias J

    2014-10-21

    We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures. © 2014 American Academy of Neurology.

  5. Spontaneous activity of isolated dopaminergic periglomerular cells of the main olfactory bulb.

    PubMed

    Puopolo, Michelino; Bean, Bruce P; Raviola, Elio

    2005-11-01

    We examined the electrophysiological properties of a population of identified dopaminergic periglomerular cells of the main olfactory bulb using transgenic mice in which catecholaminergic neurons expressed human placental alkaline phosphatase (PLAP) on the outer surface of the plasma membrane. After acute dissociation, living dopaminergic periglomerular cells were identified by a fluorescently labeled monoclonal antibody to PLAP. In current-clamp mode, dopaminergic periglomerular cells spontaneously generated action potentials in a rhythmic fashion with an average frequency of 8 Hz. The hyperpolarization-activated cation current (Ih) did not seem important for pacemaking because blocking the current with ZD 7288 or Cs+ had little effect on spontaneous firing. To investigate what ionic currents do drive pacemaking, we performed action-potential-clamp experiments using records of pacemaking as voltage command in voltage-clamp experiments. We found that substantial TTX-sensitive Na+ current flows during the interspike depolarization. In addition, substantial Ca2+ current flowed during the interspike interval, and blocking Ca2+ current hyperpolarized the neurons and stopped spontaneous firing. These results show that dopaminergic periglomerular cells have intrinsic pacemaking activity, supporting the possibility that they can maintain a tonic release of dopamine to modulate the sensitivity of the olfactory system during odor detection. Calcium entry into these neurons provides electrical drive for pacemaking as well as triggering transmitter release.

  6. Studying brain organization via spontaneous fMRI signal

    PubMed Central

    Power, Jonathan D; Schlaggar, Bradley L; Petersen, Steven E

    2014-01-01

    In recent years, some substantial advances in understanding human (and non-human) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the “resting” brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called “resting state”. This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting state fMRI has been used to delineate aspects of area-level and supra-areal brain organization. PMID:25459408

  7. Spontaneous splenic rupture in an active duty Marine upon return from Iraq: a case report

    PubMed Central

    2010-01-01

    Introduction Atraumatic splenic rupture is a rare event that has been associated with several infectious disease processes. In the active duty military population, potential exposure to these pathogens is significant. Here we discuss the case of an active duty Marine with spontaneous splenic rupture upon return from a six-month deployment in Iraq. Case presentation A previously healthy 30-year-old Caucasian male active duty Marine presented with abdominal pain, fever and diarrhea after deployment to Iraq in support of Operation Iraqi Freedom. Based on clinical and radiographic evidence, a diagnosis of spontaneous splenic rupture was ultimately suspected. After exploratory laparotomy with confirmation of rupture, splenectomy was performed, and the patient made a full, uneventful recovery. Histopathologic examination revealed mild splenomegaly with a ruptured capsule of undetermined cause. Conclusion Spontaneous splenic rupture is a rare event that may lead to life-threatening hemorrhage if not diagnosed and treated quickly. Although the cause of this patient's case was unknown, atraumatic splenic rupture has been associated with a variety of infectious diseases and demonstrates some risks the active duty military population may face while on deployment. Having an awareness of these pathogens and their role in splenic rupture, clinicians caring for military personnel must be prepared to recognize and treat this potentially fatal complication. PMID:21054871

  8. Dorsomedial prefontal cortex supports spontaneous thinking per se.

    PubMed

    Raij, T T; Riekki, T J J

    2017-06-01

    Spontaneous thinking, an action to produce, consider, integrate, and reason through mental representations, is central to our daily experience and has been suggested to serve crucial adaptive purposes. Such thinking occurs among other experiences during mind wandering that is associated with activation of the default mode network among other brain circuitries. Whether and how such brain activation is linked to the experience of spontaneous thinking per se remains poorly known. We studied 51 healthy subjects using a comprehensive experience-sampling paradigm during 3T functional magnetic resonance imaging. In comparison with fixation, the experiences of spontaneous thinking and spontaneous perception were related to activation of wide-spread brain circuitries, including the cortical midline structures, the anterior cingulate cortex and the visual cortex. In direct comparison of the spontaneous thinking versus spontaneous perception, activation was observed in the anterior dorsomedial prefrontal cortex. Modality congruence of spontaneous-experience-related brain activation was suggested by several findings, including association of the lingual gyrus with visual in comparison with non-verbal-non-visual thinking. In the context of current literature, these findings suggest that the cortical midline structures are involved in the integrative core substrate of spontaneous thinking that is coupled with other brain systems depending on the characteristics of thinking. Furthermore, involvement of the anterior dorsomedial prefrontal cortex suggests the control of high-order abstract functions to characterize spontaneous thinking per se. Hum Brain Mapp 38:3277-3288, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. Abnormal Brain Activation During Theory of Mind Tasks in Schizophrenia: A Meta-Analysis.

    PubMed

    Kronbichler, Lisa; Tschernegg, Melanie; Martin, Anna Isabel; Schurz, Matthias; Kronbichler, Martin

    2017-10-21

    Social cognition abilities are severely impaired in schizophrenia (SZ). The current meta-analysis used foci of 21 individual studies on functional abnormalities in the schizophrenic brain in order to identify regions that reveal convergent under- or over-activation during theory of mind (TOM) tasks. Studies were included in the analyses when contrasting tasks that require the processing of mental states with tasks which did not. Only studies that investigated patients with an ICD or DSM diagnosis were included. Quantitative voxel-based meta-analyses were done using Seed-based d Mapping software. Common TOM regions like medial-prefrontal cortex and temporo-parietal junction revealed abnormal activation in schizophrenic patients: Under-activation was identified in the medial prefrontal cortex, left orbito-frontal cortex, and in a small section of the left posterior temporo-parietal junction. Remarkably, robust over-activation was identified in a more dorsal, bilateral section of the temporo-parietal junction. Further abnormal activation was identified in medial occipito-parietal cortex, right premotor areas, left cingulate gyrus, and lingual gyrus. The findings of this study suggest that SZ patients simultaneously show over- and under-activation in TOM-related regions. Especially interesting, temporo-parietal junction reveals diverging activation patterns with an under-activating left posterior and an over-activating bilateral dorsal section. In conclusion, SZ patients show less specialized brain activation in regions linked to TOM and increased activation in attention-related networks suggesting compensatory effects. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  10. Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study.

    PubMed

    Pan, Wei; Gao, Xuemei; Shi, Shuo; Liu, Fuqu; Li, Chao

    2017-01-01

    A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won't significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated.

  11. Spontaneous Brain Activity Did Not Show the Effect of Violent Video Games on Aggression: A Resting-State fMRI Study

    PubMed Central

    Pan, Wei; Gao, Xuemei; Shi, Shuo; Liu, Fuqu; Li, Chao

    2018-01-01

    A great many of empirical researches have proved that longtime exposure to violent video game can lead to a series of negative effects. Although research has focused on the neural basis of the correlation between violent video game and aggression, little is known whether the spontaneous brain activity is associated with violent video game exposure. To address this question, we measured the spontaneous brain activity using resting-state functional magnetic resonance imaging (fMRI). We used the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) to quantify spontaneous brain activity. The results showed there is no significant difference in ALFF, or fALFF, between violent video game group and the control part, indicating that long time exposure to violent video games won’t significantly influence spontaneous brain activity, especially the core brain regions such as execution control, moral judgment and short-term memory. This implies the adverse impact of violent video games is exaggerated. PMID:29375416

  12. Studying brain organization via spontaneous fMRI signal.

    PubMed

    Power, Jonathan D; Schlaggar, Bradley L; Petersen, Steven E

    2014-11-19

    In recent years, some substantial advances in understanding human (and nonhuman) brain organization have emerged from a relatively unusual approach: the observation of spontaneous activity, and correlated patterns in spontaneous activity, in the "resting" brain. Most commonly, spontaneous neural activity is measured indirectly via fMRI signal in subjects who are lying quietly in the scanner, the so-called "resting state." This Primer introduces the fMRI-based study of spontaneous brain activity, some of the methodological issues active in the field, and some ways in which resting-state fMRI has been used to delineate aspects of area-level and supra-areal brain organization. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Brain modularity controls the critical behavior of spontaneous activity.

    PubMed

    Russo, R; Herrmann, H J; de Arcangelis, L

    2014-03-13

    The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

  14. Spontaneous locomotor activity and life span. A test of the rate of living theory in Drosophila melanogaster.

    PubMed

    Lints, F A; Le Bourg, E; Lints, C V

    1984-01-01

    The spontaneous locomotor activity and life span of approximately 600 individuals of both sexes and of three widely different genotypes of Drosophila melanogaster have been measured. Neither at the individual nor at the populational level could a significant correlation between spontaneous locomotor activity and life span be found. The results are discussed in relation with Pearl's [The rate of living, London University Press, London 1928] rate of living theory. That theory has been tested in relation with environmental temperature, oxygen consumption and activity. It is shown that the theory has received no definite confirmation until now.

  15. Using regional homogeneity to reveal altered spontaneous activity in patients with mild cognitive impairment.

    PubMed

    Wang, Yumei; Zhao, Xiaochuan; Xu, Shunjiang; Yu, Lulu; Wang, Lan; Song, Mei; Yang, Linlin; Wang, Xueyi

    2015-01-01

    Most patients with mild cognitive impairment (MCI) are thought to be in an early stage of Alzheimer's disease (AD). Resting-state functional magnetic resonance imaging reflects spontaneous brain activity and/or the endogenous/background neurophysiological process of the human brain. Regional homogeneity (ReHo) rapidly maps regional brain activity across the whole brain. In the present study, we used the ReHo index to explore whole brain spontaneous activity pattern in MCI. Our results showed that MCI subjects displayed an increased ReHo index in the paracentral lobe, precuneus, and postcentral and a decreased ReHo index in the medial temporal gyrus and hippocampus. Impairments in the medial temporal gyrus and hippocampus may serve as important markers distinguishing MCI from healthy aging. Moreover, the increased ReHo index observed in the postcentral and paracentral lobes might indicate compensation for the cognitive function losses in individuals with MCI.

  16. Using Regional Homogeneity to Reveal Altered Spontaneous Activity in Patients with Mild Cognitive Impairment

    PubMed Central

    Wang, Yumei; Zhao, Xiaochuan; Xu, Shunjiang; Yu, Lulu; Wang, Lan; Song, Mei; Yang, Linlin; Wang, Xueyi

    2015-01-01

    Most patients with mild cognitive impairment (MCI) are thought to be in an early stage of Alzheimer's disease (AD). Resting-state functional magnetic resonance imaging reflects spontaneous brain activity and/or the endogenous/background neurophysiological process of the human brain. Regional homogeneity (ReHo) rapidly maps regional brain activity across the whole brain. In the present study, we used the ReHo index to explore whole brain spontaneous activity pattern in MCI. Our results showed that MCI subjects displayed an increased ReHo index in the paracentral lobe, precuneus, and postcentral and a decreased ReHo index in the medial temporal gyrus and hippocampus. Impairments in the medial temporal gyrus and hippocampus may serve as important markers distinguishing MCI from healthy aging. Moreover, the increased ReHo index observed in the postcentral and paracentral lobes might indicate compensation for the cognitive function losses in individuals with MCI. PMID:25738156

  17. Signal transduction of aortic and carotid sinus baroreceptors is not modified by central command during spontaneous motor activity in decerebrate cats.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Ishida, Tomoko; Idesako, Mitsuhiro; Liang, Nan

    2014-05-15

    Our laboratory has suggested that central command provides selective inhibition of the cardiomotor component of aortic baroreflex at the start of exercise, preserving carotid sinus baroreflex. It is postulated that central command may modify the signal transduction of aortic baroreceptors, so as to decrease aortic baroreceptor input to the cardiovascular centers, and, thereby, can cause the selective inhibition of aortic baroreflex. To test the hypothesis, we directly analyzed the responses in multifiber aortic nerve activity (AoNA) and carotid sinus nerve activity (CsNA) during spontaneous motor activity in decerebrate, paralyzed cats. The increases of 62-104% in mean AoNA and CsNA were found during spontaneous motor activity, in proportion to a rise of 35 ± 3 mmHg (means ± SE) in mean arterial blood pressure (MAP), and had an attenuating tendency by restraining heart rate (HR) at the lower intrinsic frequency of 154 ± 6 beats/min. Brief occlusion of the abdominal aorta was conducted before and during spontaneous motor activity to produce a mechanically evoked increase in MAP and, thereby, to examine the stimulus-response relationship of arterial baroreceptors. Although the sensitivity of the MAP-HR baroreflex curve was markedly blunted during spontaneous motor activity, the stimulus-response relationships of AoNA and CsNA were not influenced by spontaneous motor activity, irrespective of the absence or presence of the HR restraint. Thus, it is concluded that aortic and carotid sinus baroreceptors can code beat-by-beat blood pressure during spontaneous motor activity in decerebrate cats and that central command is unlikely to modulate the signal transduction of arterial baroreceptors. Copyright © 2014 the American Physiological Society.

  18. Beta amyloid deposition and neurofibrillary tangles spontaneously occur in the brains of captive cheetahs (Acinonyx jubatus).

    PubMed

    Serizawa, S; Chambers, J K; Une, Y

    2012-03-01

    Alzheimer disease is a dementing disorder characterized pathologically by Aβ deposition, neurofibrillary tangles, and neuronal loss. Although aged animals of many species spontaneously develop Aβ deposits, only 2 species (chimpanzee and wolverine) have been reported to develop Aβ deposits and neurofibrillary tangles in the same individual. Here, the authors demonstrate the spontaneous occurrence of Aβ deposits and neurofibrillary tangles in captive cheetahs (Acinonyx jubatus). Among 22 cheetahs examined in this study, Aβ deposits were observed in 13. Immunostaining (AT8) revealed abnormal intracellular tau immunoreactivity in 10 of the cheetahs with Aβ deposits, and they were mainly distributed in the parahippocampal cortex and CA1 in a fashion similar to that in human patients with Alzheimer disease. Ultrastructurally, bundles of straight filaments filled the neuronal somata and axons, consistent with tangles. Interestingly, 2 of the cheetahs with the most severe abnormal tau immunoreactivity showed clinical cognitive dysfunction. The authors conclude that cheetahs spontaneously develop age-related neurodegenerative disease with pathologic changes similar to Alzheimer disease.

  19. Neural activation and memory for natural scenes: Explicit and spontaneous retrieval.

    PubMed

    Weymar, Mathias; Bradley, Margaret M; Sege, Christopher T; Lang, Peter J

    2018-05-06

    Stimulus repetition elicits either enhancement or suppression in neural activity, and a recent fMRI meta-analysis of repetition effects for visual stimuli (Kim, 2017) reported cross-stimulus repetition enhancement in medial and lateral parietal cortex, as well as regions of prefrontal, temporal, and posterior cingulate cortex. Repetition enhancement was assessed here for repeated and novel scenes presented in the context of either an explicit episodic recognition task or an implicit judgment task, in order to study the role of spontaneous retrieval of episodic memories. Regardless of whether episodic memory was explicitly probed or not, repetition enhancement was found in medial posterior parietal (precuneus/cuneus), lateral parietal cortex (angular gyrus), as well as in medial prefrontal cortex (frontopolar), which did not differ by task. Enhancement effects in the posterior cingulate cortex were significantly larger during explicit compared to implicit task, primarily due to a lack of functional activity for new scenes. Taken together, the data are consistent with an interpretation that medial and (ventral) lateral parietal cortex are associated with spontaneous episodic retrieval, whereas posterior cingulate cortical regions may reflect task or decision processes. © 2018 Society for Psychophysiological Research.

  20. Do positive spontaneous thoughts function as incentive salience?

    PubMed

    Rice, Elise L; Fredrickson, Barbara L

    2017-08-01

    The present work explores the theoretical relationship between positive spontaneous thoughts and incentive salience-a psychological property thought to energize wanting and approach motivation by rendering cues that are associated with enjoyment more likely to stand out to the individual when subsequently encountered in the environment (Berridge, 2007). We reasoned that positive spontaneous thoughts may at least be concomitants of incentive salience, and as such, they might likewise mediate the effect of liking on wanting. In Study 1, 103 adults recruited via Amazon's Mechanical Turk reported on key aspects of 10 everyday activities. As predicted, positive spontaneous thoughts mediated the relationship between liking an activity in the past and wanting to engage in it in the future. In Study 2, 99 undergraduate students viewed amusing and humorless cartoons and completed a thought-listing task, providing experimental evidence for the causal effect of liking on positive spontaneous thoughts. In Study 3, we tested whether positive spontaneous thoughts play an active role in energizing wanting rather than merely co-occurring with (inferred) incentive salience. In that experiment involving 80 undergraduates, participants who were led to believe that their spontaneous thoughts about a target activity were especially positive planned to devote more time to that activity over the coming week than participants who received no such information about their spontaneous thoughts. Collectively, these findings suggest that positive spontaneous thoughts may play an important role in shaping approach motivation. Broader implications and future directions in the study of positive spontaneous thoughts are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  1. A rat model of spontaneous myopathy and malignant hyperthermia.

    PubMed Central

    Gonzalez, L. E.; Meléndez-Vásquez, C. V.; Gregson, N. A.; File, S. E.

    1998-01-01

    Malignant hyperthermia is a main cause of death during general anesthesia, particularly in children. However, research has been hampered by the lack of a convenient animal model, the only one available being a special strain of pig. In this study, we describe spontaneous myopathy and a fatal syndrome of generalized muscle rigidity triggered by halothane in an outbred strain of rat. Histological examination of skeletal muscle reveals severe abnormalities indicating chronic underlying myopathy. The association of histological abnormalities with an acute, fatal syndrome clinically resembling malignant hyperthermia provides a strong basis for a new and extremely useful animal model to study this fatal disorder. Images Figure 1 Figure 2 PMID:9546371

  2. DELTAMETHRIN AND ESFENVALERATE INHIBIT SPONTANEOUS NETWORK ACTIVITY IN RAT CORTICAL NEURONS IN VITRO.

    EPA Science Inventory

    Understanding pyrethroid actions on neuronal networks will help to establish a mode of action for these compounds, which is needed for cumulative risk decisions under the Food Quality Protection Act of 1996. However, pyrethroid effects on spontaneous activity in networks of inter...

  3. A functional polymorphism of the MAOA gene modulates spontaneous brain activity in pons.

    PubMed

    Lei, Hui; Zhang, Xiaocui; Di, Xin; Rao, Hengyi; Ming, Qingsen; Zhang, Jibiao; Guo, Xiao; Jiang, Yali; Gao, Yidian; Yi, Jinyao; Zhu, Xiongzhao; Yao, Shuqiao

    2014-01-01

    To investigate the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents. Thirty-one healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H) completed the 11-item Barratt Impulsiveness Scale (BIS-11) questionnaire and were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software. ALFF data were related to BIS scores and compared between genotype groups. Compared with the MAOA-H group, the MAOA-L group showed significantly lower ALFFs in the pons. There was a significant correlation between the BIS scores and the ALFF values in the pons for MAOA-L group, but not for the MAOA-H group. Further regression analysis showed a significant genotype by ALFF values interaction effect on BIS scores. Lower spontaneous brain activity in the pons of the MAOA-L male adolescents may provide a neural mechanism by which boys with the MAOA-L genotype confers risk for impulsivity and aggression.

  4. Alteration of Spontaneous Brain Activity After Hypoxia-Reoxygenation: A Resting-State fMRI Study.

    PubMed

    Zhang, Jiaxing; Chen, Ji; Fan, Cunxiu; Li, Jinqiang; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2017-03-01

    Zhang, Jiaxing, Ji Chen, Cunxiu Fan, Jinqiang Li, Jianzhong Lin, Tianhe Yang, and Ming Fan. Alteration of spontaneous brain activity after hypoxia-reoxygenation: A resting-state fMRI study. High Alt Med Biol. 18:20-26, 2017.-The present study was designed to investigate the effect of hypoxia-reoxygenation on the spontaneous neuronal activity in brain. Sixteen sea-level (SL) soldiers (20.5 ± 0.7 years), who garrisoned the frontiers in high altitude (HA) (2300-4400 m) for two years and subsequently descended to sea level for one to seven days, were recruited. Control group consisted of 16 matched SL natives. The amplitude of low-frequency fluctuations (ALFF) of regional brain functional magnetic resonance imaging signal in resting state and functional connectivity (FC) between brain regions was analyzed. HA subjects showed significant increases of ALFF at several sites within the bilateral occipital cortices and significant decreases of ALFF in the right anterior insula and extending to the caudate, putamen, inferior frontal orbital cortex, temporal pole, and superior temporal gyrus; lower ALFF values in the right insula were positively correlated with low respiratory measurements. The right insula in HA subjects had increases of FC with the right superior temporal gyrus, postcentral gyrus, rolandic operculum, supramarginal gyrus, and inferior frontal triangular area. We thus demonstrated that hypoxia-reoxygenation had influence on the spontaneous neuronal activity in brain. The decrease of insular neuronal activity may be related to the reduction of ventilatory drive, while the increase of FC with insula may indicate a central compensation.

  5. Abnormal proliferation of CD4- CD8+ gammadelta+ T cells with chromosome 6 anomaly: role of Fas ligand expression in spontaneous regression of the cells.

    PubMed

    Ichikawa, N; Kitano, K; Ito, T; Nakazawa, T; Shimodaira, S; Ishida, F; Kiyosawa, K

    1999-04-01

    We report a case of granular lymphocyte proliferative disorder accompanied with hemolytic anemia and neutropenia. Phenotypes of the cells were T cell receptor gammadelta+ CD3+ CD4- CD8+ CD16+ CD56- CD57-. Southern blot analysis of T cell receptor beta and gamma chains demonstrated rearranged bands in both. Chromosomal analysis after IL-2 stimulation showed deletion of chromosome 6. Sorted gammadelta+ T cells showed an increase in Fas ligand expression compared with the levels in sorted alphabeta+ T cells. The expression of Fas ligand on these gammadelta+ T cells increased after IL-2 stimulation. The patient's anemia improved along with a decrease in granular lymphocyte count and disappearance of the abnormal karyotype without treatment. The expression of Fas ligand may be involved in spontaneous regression of granular lymphocyte proliferation with hemolytic anemia.

  6. Generation of an induced pluripotent stem cell line from chorionic villi of a Turner syndrome spontaneous abortion.

    PubMed

    Parveen, Shagufta; Panicker, M M; Gupta, Pawan Kumar

    2017-03-01

    A major cause of spontaneous abortions is chromosomal abnormality of foetal cells. We report the generation of an induced pluripotent stem cell line from the fibroblasts isolated from chorionic villi of an early spontaneously aborted foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem cell line is transgene free, retains the original XO karyotype, expresses pluripotency markers and undergoes trilineage differentiation. This pluripotent stem cell model of Turner syndrome should serve as a tool to study the developmental abnormalities of foetus and placenta that lead to early embryo lethality and profound symptoms like infertility in 45 XO survivors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Acquired granulocyte abnormality during drug allergic reactions: possible role of complement activation.

    PubMed

    Bowers, T K; Craddock, P R; Jacob, H S

    1977-01-01

    A profound defect in granulocyte chemotaxis was documented in an otherwise healthy 21-yr-old man who failed to localize granulocytes to an area of cellulitis during an allergic reaction to cephalothin. During the period of drug allergy, characterized by urticaria, eosinophilia, and profound hypocomplementemia, in vitro migration of the patient's granulocytes in the Boyden chamber was markedly impaired. Although devoid of hemolytic complement activity, the patient's serum possessed supranormal chemotactic activity, even following heat inactivation, suggesting the presence of chemotactically active complement split products. Chemotactic function improved concomitantly with steroid therapy and normalization of serum complement levels, and was entirely normal following clinical recovery and cessation of steroid therapy. The chemotactic abnormality noted in the patient's cells was reproduced in normal granulocytes by preincubation either with patient serum or with cobra venom-activated fresh (but not heated) normal serum, suggesting that in vivo exposure of granulocytes to activated complement was responsible for the patient's abnormal chemotactic response. This mechanism may contribute to the increased infection propensity noted in other conditions characterized by in vivo complement activation, such as rheumatoid arthritis and systemic lupus erythematosis.

  8. Spontaneous regression of neuroblastoma.

    PubMed

    Brodeur, Garrett M

    2018-05-01

    Neuroblastomas are characterized by heterogeneous clinical behavior, from spontaneous regression or differentiation into a benign ganglioneuroma, to relentless progression despite aggressive, multimodality therapy. Indeed, neuroblastoma is unique among human cancers in terms of its propensity to undergo spontaneous regression. The strongest evidence for this comes from the mass screening studies conducted in Japan, North America and Europe and it is most evident in infants with stage 4S disease. This propensity is associated with a pattern of genomic change characterized by whole chromosome gains rather than segmental chromosome changes but the mechanism(s) underlying spontaneous regression are currently a matter of speculation. There is evidence to support several possible mechanisms of spontaneous regression in neuroblastomas: (1) neurotrophin deprivation, (2) loss of telomerase activity, (3) humoral or cellular immunity and (4) alterations in epigenetic regulation and possibly other mechanisms. It is likely that a better understanding of the mechanisms of spontaneous regression will help to identify targeted therapeutic approaches for these tumors. The most easily targeted mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A (TrkA) pathway. Pan-Trk inhibitors are currently in clinical trials and so Trk inhibition might be used as the first line of therapy in infants with biologically favorable tumors that require treatment. Alternative approaches consist of breaking immune tolerance to tumor antigens but approaches to telomere shortening or epigenetic regulation are not easily druggable. The different mechanisms of spontaneous neuroblastoma regression are reviewed here, along with possible therapeutic approaches.

  9. Spontaneous symmetry breaking in active droplets provides a generic route to motility

    PubMed Central

    Tjhung, Elsen; Marenduzzo, Davide; Cates, Michael E.

    2012-01-01

    We explore a generic mechanism whereby a droplet of active matter acquires motility by the spontaneous breakdown of a discrete symmetry. The model we study offers a simple representation of a “cell extract” comprising, e.g., a droplet of actomyosin solution. (Such extracts are used experimentally to model the cytoskeleton). Actomyosin is an active gel whose polarity describes the mean sense of alignment of actin fibres. In the absence of polymerization and depolymerization processes (‘treadmilling’), the gel’s dynamics arises solely from the contractile motion of myosin motors; this should be unchanged when polarity is inverted. Our results suggest that motility can arise in the absence of treadmilling, by spontaneous symmetry breaking (SSB) of polarity inversion symmetry. Adapting our model to wall-bound cells in two dimensions, we find that as wall friction is reduced, treadmilling-induced motility falls but SSB-mediated motility rises. The latter might therefore be crucial in three dimensions where frictional forces are likely to be modest. At a supracellular level, the same generic mechanism can impart motility to aggregates of nonmotile but active bacteria; we show that SSB in this (extensile) case leads generically to rotational as well as translational motion. PMID:22797894

  10. Increased production of active ghrelin is relevant to hyperphagia in nonobese spontaneously diabetic Torii rats.

    PubMed

    Mifune, Hiroharu; Nishi, Yoshihiro; Tajiri, Yuji; Masuyama, Taku; Hosoda, Hiroshi; Kangawa, Kenji; Kojima, Masayasu

    2012-04-01

    An abnormal eating behavior is often associated with diabetes mellitus in individuals. In the present study, we investigated the mechanisms underlying the relationship among uncontrolled diabetes, food intake, and the production of ghrelin, an orexigenic hormone, in spontaneous diabetic Torii (SDT) rats. Male SDT rats and age-matched control Sprague-Dawley (SD) rats were housed from 8 to 38 weeks of age. Body weight and daily food intake were measured weekly, whereas blood and whole stomach samples were obtained at the age of 8, 25, and 38 weeks in both SDT and SD rats. The SDT rats at both 25 and 38 weeks of age demonstrated significantly lower body weights despite almost doubled food consumption compared with the SD rats of the same age. The SDT rats showed overt hyperglycemia at 25 and 38 weeks of age with concomitant hypoinsulinemia. The plasma active ghrelin levels and the ratio to total ghrelin levels of SDT rats at 38 weeks of age were significantly higher than those of SD rats of the same age. Stomach ghrelin and ghrelin O-acyltransferase messenger RNA expression levels were higher in SDT rats than in SD rats after the induction of diabetes, with a concomitant decrease of stomach ghrelin-immunopositive cell numbers in SDT rats at 38 weeks of age. The SDT rats with uncontrolled hyperglycemia show hyperphagia with a concomitant increase of plasma active ghrelin concentration. This report is the first to clarify the relevance of ghrelin to hyperphagia in diabetic state over an extended period. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Spontaneous Eye-Blinking and Stereotyped Behavior in Older Persons with Mental Retardation

    ERIC Educational Resources Information Center

    Roebel, Amanda M.; MacLean, William E., Jr.

    2007-01-01

    Previous research indicates that abnormal stereotyped movements are associated with central dopamine dysfunction and that eye-blink rate is a noninvasive, in vivo measure of dopamine function. We measured the spontaneous eye-blinking and stereotyped behavior of older adults with severe/profound mental retardation living in a state mental…

  12. Abnormal medial prefrontal cortex activity in heavy cannabis users during conscious emotional evaluation.

    PubMed

    Wesley, Michael J; Lile, Joshua A; Hanlon, Colleen A; Porrino, Linda J

    2016-03-01

    Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Functional magnetic resonance imaging (fMRI) was used to examine brain activity as cannabis users (N = 16) and non-cannabis-using controls (N = 17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load.

  13. Inhibition of spontaneous activity of rabbit atrioventricular node cells by KB-R7943 and inhibitors of sarcoplasmic reticulum Ca2+ ATPase

    PubMed Central

    Cheng, Hongwei; Smith, Godfrey L.; Hancox, Jules C.; Orchard, Clive H.

    2011-01-01

    The atrioventricular node (AVN) can act as a subsidiary cardiac pacemaker if the sinoatrial node fails. In this study, we investigated the effects of the Na–Ca exchange (NCX) inhibitor KB-R7943, and inhibition of the sarcoplasmic reticulum calcium ATPase (SERCA), using thapsigargin or cyclopiazonic acid (CPA), on spontaneous action potentials (APs) and [Ca2+]i transients from cells isolated from the rabbit AVN. Spontaneous [Ca2+]i transients were monitored from undialysed AVN cells at 37 °C using Fluo-4. In separate experiments, spontaneous APs and ionic currents were recorded using the whole-cell patch clamp technique. Rapid application of 5 μM KB-R7943 slowed or stopped spontaneous APs and [Ca2+]i transients. However, in voltage clamp experiments in addition to blocking NCX current (INCX) KB-R7943 partially inhibited L-type calcium current (ICa,L). Rapid reduction of external [Na+] also abolished spontaneous activity. Inhibition of SERCA (using 2.5 μM thapsigargin or 30 μM CPA) also slowed or stopped spontaneous APs and [Ca2+]i transients. Our findings are consistent with the hypothesis that sarcoplasmic reticulum (SR) Ca2+ release influences spontaneous activity in AVN cells, and that this occurs via [Ca2+]i-activated INCX; however, the inhibitory action of KB-R7943 on ICa,L means that care is required in the interpretation of data obtained using this compound. PMID:21163524

  14. Plasma folate levels and risk of spontaneous abortion.

    PubMed

    George, Lena; Mills, James L; Johansson, Anna L V; Nordmark, Anna; Olander, Bodil; Granath, Fredrik; Cnattingius, Sven

    2002-10-16

    Both folate deficiency and folic acid supplements have been reported to increase the risk of spontaneous abortion. The results are inconclusive, however, and measurements of folate have not been available in all studies. To study the association between plasma folate levels and the risk of spontaneous abortion. Population-based, matched, case-control study of case women with spontaneous abortion and control women from January 1996 through December 1998 in Uppsala County, Sweden. Plasma folate measurements were available for 468 cases and 921 controls at 6 to 12 gestational weeks. Risk of spontaneous abortion vs maternal plasma folate level. Compared with women with plasma folate levels between 2.20 and 3.95 ng/mL (5.0 and 8.9 nmol/L), women with low (< or =2.19 ng/mL [< or =4.9 nmol/L]) folate levels were at increased risk of spontaneous abortion (adjusted odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01-2.14), whereas women with higher folate levels (3.96-6.16 ng/mL [9.0-13.9 nmol/L] and > or =6.17 ng/mL [> or =14.0 nmol/L]) showed no increased risk of spontaneous abortion (OR, 0.84; 95% CI, 0.59-1.20; and OR, 0.74; 95% CI, 0.47-1.16, respectively). Low folate levels were associated with a significantly increased risk when the fetal karyotype was abnormal (OR, 1.95; 95% CI, 1.09-3.48) but not when the fetal karyotype was normal (OR, 1.11; 95% CI, 0.55-2.24) or unknown (OR, 1.45; 95% CI, 0.90-2.33). Low plasma folate levels were associated with an increased risk of early spontaneous abortion.

  15. A Functional Polymorphism of the MAOA Gene Modulates Spontaneous Brain Activity in Pons

    PubMed Central

    Lei, Hui; Zhang, Xiaocui; Di, Xin; Rao, Hengyi; Ming, Qingsen; Zhang, Jibiao; Guo, Xiao; Jiang, Yali; Gao, Yidian; Yi, Jinyao; Zhu, Xiongzhao; Yao, Shuqiao

    2014-01-01

    Objective. To investigate the effects of a functional polymorphism of the monoamine oxidase A (MAOA) gene on spontaneous brain activity in healthy male adolescents. Methods. Thirty-one healthy male adolescents with the low-activity MAOA genotype (MAOA-L) and 25 healthy male adolescents with the high-activity MAOA genotype (MAOA-H) completed the 11-item Barratt Impulsiveness Scale (BIS-11) questionnaire and were subjected to resting-state functional magnetic resonance imaging (rs-fMRI) scans. The amplitude of low-frequency fluctuation (ALFF) of the blood oxygen level-dependent (BOLD) signal was calculated using REST software. ALFF data were related to BIS scores and compared between genotype groups. Results. Compared with the MAOA-H group, the MAOA-L group showed significantly lower ALFFs in the pons. There was a significant correlation between the BIS scores and the ALFF values in the pons for MAOA-L group, but not for the MAOA-H group. Further regression analysis showed a significant genotype by ALFF values interaction effect on BIS scores. Conclusions. Lower spontaneous brain activity in the pons of the MAOA-L male adolescents may provide a neural mechanism by which boys with the MAOA-L genotype confers risk for impulsivity and aggression. PMID:24971323

  16. Efficacy of first-trimester ultrasound parameters for prediction of early spontaneous abortion.

    PubMed

    Datta, Mamta Rath; Raut, Ankush

    2017-09-01

    To assess first-trimester ultrasound measurements for the prediction of early spontaneous abortion. In a prospective observational study in Jamshedpur, India, women with singleton pregnancies of 42-76 days were enrolled between November 2014 and April 2016. Inclusion criteria were spontaneous conception, embryonic cardiac activity, and regular menstrual cycle. Fetal crown-to-rump length (CRL), gestational sac diameter (GSD), yolk sac diameter (YSD), and fetal heart rate (FHR) were measured by transvaginal ultrasonography. Ultrasonography was repeated at 12 weeks and beyond to determine pregnancy continuation. Among 800 women, 140 (17.5%) experienced early spontaneous abortion. CRL, GSD, and FHR values below the 5th percentile (odds ratio [OR] 26.48, 26.94, and 100.63, respectively), and YSD above the 95th percentile (OR 1.04) were predictors of early abortion. Normal YSD did not reduce the risk of abortion if the other three parameters were below the 5th percentile (OR 34.27). For every 10-bpm decrease in FHR below 130, there was 26.7% increased risk of abortion. GSD-CRL difference of less than 5 mm was associated with a higher likelihood of abortion (OR 4.88). First-trimester ultrasound measurements are predictors of early abortion. Risk assessment tables based on combinations of abnormal measures might improve prediction rates. © 2017 International Federation of Gynecology and Obstetrics.

  17. [Effects of reversing the feeding cycle and the light period on the spontaneous activity of the rat (author's transl)].

    PubMed

    Ticca, M

    1976-01-01

    The amount and the circadian distribution of spontaneous activity in the rat are influenced by a number of factors, whose importance and interrelationships are still deeply discussed. In order to check the reliability of previous studies about the effects of meal-eating on the spontaneous activity (wheel running) of rats of our Sprague-Dawley strain, the adjustment to the modifications of the normal day-night cycle and of the normal nocturnal feeding rhythm have been controlled. Reversing the normal light and dark periods caused the rats, after a 24 hours period, to lower and to irregularly distribute their spontaneous activity. Rats shifted their pattern of maximal activity by 12 hours in the new period of darkness in about five days, and showed to have completely fixed the new reversed running habit. Also feeding habits changed in a similar way, but more slowly. The levels of mean daily activity did not change. In a second experiment, rats, received food during light hours, and were deprived during dark hours. Their activity increased considerably and irregularly during dark hours, while a very slight rise of wheel running was shown during light hours. Body weight gain and food consumption were similar to those of the control group. These results slightly differ from those obtained using other rat strains, and are an interesting example of reinforcement of a spontaneous behavior resulting more from the light-dark cycle than from cues provided by food deprivation.

  18. Altered spontaneous neural activity in the occipital face area reflects behavioral deficits in developmental prosopagnosia.

    PubMed

    Zhao, Yuanfang; Li, Jingguang; Liu, Xiqin; Song, Yiying; Wang, Ruosi; Yang, Zetian; Liu, Jia

    2016-08-01

    Individuals with developmental prosopagnosia (DP) exhibit severe difficulties in recognizing faces and to a lesser extent, also exhibit difficulties in recognizing non-face objects. We used fMRI to investigate whether these behavioral deficits could be accounted for by altered spontaneous neural activity. Two aspects of spontaneous neural activity were measured: the intensity of neural activity in a voxel indexed by the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), and the connectivity of a voxel to neighboring voxels indexed by regional homogeneity (ReHo). Compared with normal adults, both the fALFF and ReHo values within the right occipital face area (rOFA) were significantly reduced in DP subjects. Follow-up studies on the normal adults revealed that these two measures indicated further functional division of labor within the rOFA. The fALFF in the rOFA was positively correlated with behavioral performance in recognition of non-face objects, whereas ReHo in the rOFA was positively correlated with processing of faces. When considered together, the altered fALFF and ReHo within the same region (rOFA) may account for the comorbid deficits in both face and object recognition in DPs, whereas the functional division of labor in these two measures helps to explain the relative independency of deficits in face recognition and object recognition in DP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Spontaneous anterior chamber hemorrhage from the iris: a unique cinematographic documentation.

    PubMed Central

    Welch, R B

    1980-01-01

    A 54-year-old white female was observed with an apparent spontaneous idiopathic anterior chamber hemorrhage from the pupillary border of the iris. This event was documented by cinematography. A review of the literature concerning anterior chamber hemorrhage is presented and reports of spontaneous hyphema enumerated. The relationship of the entity of pupillary vascular tufts to the present report are discussed and etiologic factors considered. It is apparent that closer scrutiny of the pupillary border should be performed and iris angiography obtained in a variety of eyes to delineate normal and abnormal variants. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 PMID:6167051

  20. Cerebral cortical neurons with activity linked to central neurogenic spontaneous and evoked elevations in cerebral blood flow

    NASA Technical Reports Server (NTRS)

    Golanov, E. V.; Reis, D. J.

    1996-01-01

    We recorded neurons in rat cerebral cortex with activity relating to the neurogenic elevations in regional cerebral blood flow (rCBF) coupled to stereotyped bursts of EEG activity, burst-cerebrovascular wave complexes, appearing spontaneously or evoked by electrical stimulation of rostral ventrolateral medulla (RVL) or fastigial nucleus (FN). Of 333 spontaneously active neurons only 15 (5%), in layers 5-6, consistently (P < 0.05, chi-square) increased their activity during the earliest potential of the complex, approximately 1.3 s before the rise of rCBF, and during the minutes-long elevation of rCBF elicited by 10 s of stimulation of RVL or FN. The results indicate the presence of a small population of neurons in deep cortical laminae whose activity correlates with neurogenic elevations of rCBF. These neurons may function to transduce afferent neuronal signals into vasodilation.

  1. [Monilethrix--rare syndrome of structural hair abnormalities].

    PubMed

    Brzezińska-Wcisło, L; Bogdanowski, T; Szeremeta-Bazylewicz, G; Pierzchała, E

    1999-11-01

    Monilethrix is a rare structural disorder of hair. Characteristic abnormalities in the form of alternating thinning and fusiform thickening are observed in most of hair shafts that we call beaded hair. Macroscopic estimation shows lustreless, dry, rough, fragile hair. Trichological examination usually reveals a considerable percentage of anagenic hair. According to our own experiences and literature data systemic therapy (vitamins) and topical treatment (desquamative ointments) are not effective sufficiently. Spontaneous regression of symptoms often appears with time. Five cases of familial occurrence of monilethrix have been presented.

  2. Myofascial trigger points: spontaneous electrical activity and its consequences for pain induction and propagation

    PubMed Central

    2011-01-01

    Active myofascial trigger points are one of the major peripheral pain generators for regional and generalized musculoskeletal pain conditions. Myofascial trigger points are also the targets for acupuncture and/or dry needling therapies. Recent evidence in the understanding of the pathophysiology of myofascial trigger points supports The Integrated Hypothesis for the trigger point formation; however unanswered questions remain. Current evidence shows that spontaneous electrical activity at myofascial trigger point originates from the extrafusal motor endplate. The spontaneous electrical activity represents focal muscle fiber contraction and/or muscle cramp potentials depending on trigger point sensitivity. Local pain and tenderness at myofascial trigger points are largely due to nociceptor sensitization with a lesser contribution from non-nociceptor sensitization. Nociceptor and non-nociceptor sensitization at myofascial trigger points may be part of the process of muscle ischemia associated with sustained focal muscle contraction and/or muscle cramps. Referred pain is dependent on the sensitivity of myofascial trigger points. Active myofascial trigger points may play an important role in the transition from localized pain to generalized pain conditions via the enhanced central sensitization, decreased descending inhibition and dysfunctional motor control strategy. PMID:21439050

  3. Active Tuning of Spontaneous Emission by Mie-Resonant Dielectric Metasurfaces.

    PubMed

    Bohn, Justus; Bucher, Tobias; Chong, Katie E; Komar, Andrei; Choi, Duk-Yong; Neshev, Dragomir N; Kivshar, Yuri S; Pertsch, Thomas; Staude, Isabelle

    2018-06-13

    Mie-resonant dielectric metasurfaces offer comprehensive opportunities for the manipulation of light fields with high efficiency. Additionally, various strategies for the dynamic tuning of the optical response of such metasurfaces were demonstrated, making them important candidates for reconfigurable optical devices. However, dynamic control of the light-emission properties of active Mie-resonant dielectric metasurfaces by an external control parameter has not been demonstrated so far. Here, we experimentally demonstrate the dynamic tuning of spontaneous emission from a Mie-resonant dielectric metasurface that is situated on a fluorescent substrate and embedded into a liquid crystal cell. By switching the liquid crystal from the nematic state to the isotropic state via control of the cell temperature, we induce a shift of the spectral position of the metasurface resonances. This results in a change of the local photonic density of states, which, in turn, governs the enhancement of spontaneous emission from the substrate. Specifically, we observe spectral tuning of both the electric and magnetic dipole resonances, resulting in a 2-fold increase of the emission intensity at λ ≈ 900 nm. Our results demonstrate a viable strategy to realize flat tunable light sources based on dielectric metasurfaces.

  4. Abnormal Medial Prefrontal Cortex Activity in Heavy Cannabis Users During Conscious Emotional Evaluation

    PubMed Central

    Lile, Joshua A.; Hanlon, Colleen A.; Porrino, Linda J.

    2015-01-01

    Rationale Long-term heavy cannabis users (cannabis users) who are not acutely intoxicated have diminished subconscious neural responsiveness to affective stimuli. Objective This study sought to determine if abnormal processing extends to the conscious evaluation of emotional stimuli. Methods Functional Magnetic Resonance Imaging (fMRI) was used to examine brain activity as cannabis users (N=16) and non-cannabis using controls (N=17) evaluated and categorized standardized International Affective Picture System (IAPS) stimuli. Individual judgments were used to isolate activity during the evaluation of emotional (i.e., emotional evaluation) or neutral (i.e., neutral evaluation) stimuli. Within- and between-group analyses were performed. Results Both groups judged the same stimuli as emotional and had activations in visual, midbrain, and middle cingulate cortices during emotional evaluation, relative to neutral. Within-group analyses also revealed amygdalar and inferior frontal gyrus activations in controls, but not cannabis users, and medial prefrontal cortex (mPFC) deactivations in cannabis users, but not controls, during emotional evaluation, relative to neutral. Between-group comparisons found that mPFC activity during positive and negative evaluation was significantly hypoactive in cannabis users, relative to controls. Conclusions Abnormal neural processing of affective content extends to the level of consciousness in cannabis users. The hypoactive mPFC responses observed resembles the attenuated mPFC responses found during increased non-affective cognitive load in prior research. These findings suggest that abnormal mPFC singling in cannabis users during emotional evaluation might be associated with increased non-affective cognitive load. PMID:26690589

  5. Dimensionality and entropy of spontaneous and evoked rate activity

    NASA Astrophysics Data System (ADS)

    Engelken, Rainer; Wolf, Fred

    Cortical circuits exhibit complex activity patterns both spontaneously and evoked by external stimuli. Finding low-dimensional structure in population activity is a challenge. What is the diversity of the collective neural activity and how is it affected by an external stimulus? Using concepts from ergodic theory, we calculate the attractor dimensionality and dynamical entropy production of these networks. We obtain these two canonical measures of the collective network dynamics from the full set of Lyapunov exponents. We consider a randomly-wired firing-rate network that exhibits chaotic rate fluctuations for sufficiently strong synaptic weights. We show that dynamical entropy scales logarithmically with synaptic coupling strength, while the attractor dimensionality saturates. Thus, despite the increasing uncertainty, the diversity of collective activity saturates for strong coupling. We find that a time-varying external stimulus drastically reduces both entropy and dimensionality. Finally, we analytically approximate the full Lyapunov spectrum in several limiting cases by random matrix theory. Our study opens a novel avenue to characterize the complex dynamics of rate networks and the geometric structure of the corresponding high-dimensional chaotic attractor. received funding from Evangelisches Studienwerk Villigst, DFG through CRC 889 and Volkswagen Foundation.

  6. Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

    PubMed

    Kita, Hitoshi; Kita, Takako

    2011-07-13

    The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

  7. Transvenous embolization in spontaneous direct carotid-cavernous fistula in childhood

    PubMed Central

    Mercado, Glenna B.; Irie, Keiko; Negoro, Makoto; Moriya, Shigeta; Tanaka, Teppei; Ohmura, Masahiro; Sadato, Akiyo; Hayakawa, Motuharu; Sano, Hirotoshi

    2011-01-01

    Carotid cavernous fistula (CCF) is an abnormal arteriovenous communication in the cavernous sinus. Direct CCF results from a tear in the intracavernous carotid artery. Typically, it has a high flow and usually presents with oculo-orbital venous congestive features such as exophthalmos, chemosis, and sometimes oculomotor or abducens cranial nerve palsy. Indirect CCF generally occurs spontaneously with subtle signs. We report a rare case of spontaneous direct CCF in childhood who did not have the usual history of craniofacial trauma or connective tissue disorder but presented with progressive chemosis and exophthalmos of the right eye. This report aims also to describe the safety and success of transvenous embolization with coils of the superior ophthalmic vein and cavernous sinus through the inferior petrosal sinus. PMID:22059104

  8. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity.

    PubMed

    Chen, Hua-Jun; Zhang, Ling; Jiang, Long-Feng; Chen, Qiu-Feng; Li, Jun; Shi, Hai-Bin

    2016-08-01

    It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.

  9. Cholinergic Interneurons Underlie Spontaneous Dopamine Release in Nucleus Accumbens

    PubMed Central

    2017-01-01

    The release of dopamine from terminals in the NAc is regulated by a number of factors, including voltage-gated ion channels, D2-autoreceptors, and nAChRs. Cholinergic interneurons (CINs) drive dopamine release through activation of nAChRs on dopamine terminals. Using cyclic voltammetry in mouse brain slices, nAChR-dependent spontaneous dopamine transients and the mechanisms underlying the origin were examined in the NAc. Spontaneous events were infrequent (0.3 per minute), but the rate and amplitude were increased after blocking Kv channels with 4-aminopyridine. Although the firing frequency of CINs was increased by blocking glutamate reuptake with TBOA and the Sk blocker apamin, only 4-aminopyridine increased the frequency of dopamine transients. In contrast, inhibition of CIN firing with the μ/δ selective opioid [Met5]enkephalin (1 μm) decreased spontaneous dopamine transients. Cocaine increased the rate and amplitude of dopamine transients, suggesting that the activity of the dopamine transporter limits the detection of these events. In the presence of cocaine, the rate of spontaneous dopamine transients was further increased after blocking D2-autoreceptors. Blockade of muscarinic receptors had no effect on evoked dopamine release, suggesting that feedback inhibition of acetylcholine release was not involved. Thus, although spontaneous dopamine transients are reliant on nAChRs, the frequency was not strictly governed by the activity of CINs. The increase in frequency of spontaneous dopamine transients induced by cocaine was not due to an increase in cholinergic tone and is likely a product of an increase in detection resulting from decreased dopamine reuptake. SIGNIFICANCE STATEMENT The actions of dopamine in the NAc are thought to be responsible for endogenous reward and the reinforcing properties of drugs of abuse, such as psychostimulants. The present work examines the mechanisms underlying nAChR-induced spontaneous dopamine release. This study

  10. Altered spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder: A resting-state fMRI study.

    PubMed

    Zhu, Xi; He, Zhongqiong; Luo, Cheng; Qiu, Xiangmiao; He, Shixu; Peng, Anjiao; Zhang, Lin; Chen, Lei

    2018-03-15

    To investigate alterations in spontaneous brain activity in MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder using resting-state functional magnetic resonance imaging (RS-fMRI). Eighteen MRI-negative refractory temporal lobe epilepsy patients with major depressive disorder (PDD), 17 MRI-negative refractory temporal lobe epilepsy patients without major depressive disorder (nPDD), and 21 matched healthy controls (HC) were recruited from West China Hospital of SiChuan University from April 2016 to June 2017. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and 17-item Hamilton Depression Rating Scale were employed to confirm the diagnosis of major depressive disorder and assess the severity of depression. All participants underwent RS-fMRI scans using a 3.0T MRI system. MRI data were compared and analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) to measure spontaneous brain activity. These two methods were both used to evaluate spontaneous cerebral activity. The PDD group showed significantly altered spontaneous brain activity in the bilateral mesial prefrontal cortex, precuneus, angular gyrus, right parahippocampal gyrus, and right temporal pole. Meanwhile, compared with HC, the nPDD group demonstrated altered spontaneous brain activity in the temporal neocortex but no changes in mesial temporal structures. The PDD group showed regional brain activity alterations in the prefrontal-limbic system and dysfunction of the default mode network. The underlying pathophysiology of PDD may be provided for further studies. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Experimental Zika Virus Infection in the Pregnant Common Marmoset Induces Spontaneous Fetal Loss and Neurodevelopmental Abnormalities.

    PubMed

    Seferovic, Maxim; Martín, Claudia Sánchez-San; Tardif, Suzette D; Rutherford, Julienne; Castro, Eumenia C C; Li, Tony; Hodara, Vida L; Parodi, Laura M; Giavedoni, Luis; Layne-Colon, Donna; Tamhankar, Manasi; Yagi, Shigeo; Martyn, Calla; Reyes, Kevin; Suter, Melissa A; Aagaard, Kjersti M; Chiu, Charles Y; Patterson, Jean L

    2018-05-01

    During its most recent outbreak across the Americas, Zika virus (ZIKV) was surprisingly shown to cause fetal loss and congenital malformations in acutely and chronically infected pregnant women. However, understanding the underlying pathogenesis of ZIKV congenital disease has been hampered by a lack of relevant in vivo experimental models. Here we present a candidate New World monkey model of ZIKV infection in pregnant marmosets that faithfully recapitulates human disease. ZIKV inoculation at the human-equivalent of early gestation caused an asymptomatic seroconversion, induction of type I/II interferon-associated genes and proinflammatory cytokines, and persistent viremia and viruria. Spontaneous pregnancy loss was observed 16-18 days post-infection, with extensive active placental viral replication and fetal neurocellular disorganization similar to that seen in humans. These findings underscore the key role of the placenta as a conduit for fetal infection, and demonstrate the utility of marmosets as a highly relevant model for studying congenital ZIKV disease and pregnancy loss.

  12. Abnormal Auditory Gain in Hyperacusis: Investigation with a Computational Model

    PubMed Central

    Diehl, Peter U.; Schaette, Roland

    2015-01-01

    Hyperacusis is a frequent auditory disorder that is characterized by abnormal loudness perception where sounds of relatively normal volume are perceived as too loud or even painfully loud. As hyperacusis patients show decreased loudness discomfort levels (LDLs) and steeper loudness growth functions, it has been hypothesized that hyperacusis might be caused by an increase in neuronal response gain in the auditory system. Moreover, since about 85% of hyperacusis patients also experience tinnitus, the conditions might be caused by a common mechanism. However, the mechanisms that give rise to hyperacusis have remained unclear. Here, we have used a computational model of the auditory system to investigate candidate mechanisms for hyperacusis. Assuming that perceived loudness is proportional to the summed activity of all auditory nerve (AN) fibers, the model was tuned to reproduce normal loudness perception. We then evaluated a variety of potential hyperacusis gain mechanisms by determining their effects on model equal-loudness contours and comparing the results to the LDLs of hyperacusis patients with normal hearing thresholds. Hyperacusis was best accounted for by an increase in non-linear gain in the central auditory system. Good fits to the average patient LDLs were obtained for a general increase in gain that affected all frequency channels to the same degree, and also for a frequency-specific gain increase in the high-frequency range. Moreover, the gain needed to be applied after subtraction of spontaneous activity of the AN, which is in contrast to current theories of tinnitus generation based on amplification of spontaneous activity. Hyperacusis and tinnitus might therefore be caused by different changes in neuronal processing in the central auditory system. PMID:26236277

  13. Reconstruction of human brain spontaneous activity based on frequency-pattern analysis of magnetoencephalography data

    PubMed Central

    Llinás, Rodolfo R.; Ustinin, Mikhail N.; Rykunov, Stanislav D.; Boyko, Anna I.; Sychev, Vyacheslav V.; Walton, Kerry D.; Rabello, Guilherme M.; Garcia, John

    2015-01-01

    A new method for the analysis and localization of brain activity has been developed, based on multichannel magnetic field recordings, over minutes, superimposed on the MRI of the individual. Here, a high resolution Fourier Transform is obtained over the entire recording period, leading to a detailed multi-frequency spectrum. Further analysis implements a total decomposition of the frequency components into functionally invariant entities, each having an invariant field pattern localizable in recording space. The method, addressed as functional tomography, makes it possible to find the distribution of magnetic field sources in space. Here, the method is applied to the analysis of simulated data, to oscillating signals activating a physical current dipoles phantom, and to recordings of spontaneous brain activity in 10 healthy adults. In the analysis of simulated data, 61 dipoles are localized with 0.7 mm precision. Concerning the physical phantom the method is able to localize three simultaneously activated current dipoles with 1 mm precision. Spatial resolution 3 mm was attained when localizing spontaneous alpha rhythm activity in 10 healthy adults, where the alpha peak was specified for each subject individually. Co-registration of the functional tomograms with each subject's head MRI localized alpha range activity to the occipital and/or posterior parietal brain region. This is the first application of this new functional tomography to human brain activity. The method successfully provides an overall view of brain electrical activity, a detailed spectral description and, combined with MRI, the localization of sources in anatomical brain space. PMID:26528119

  14. Abnormal activity in reward brain circuits in human narcolepsy with cataplexy.

    PubMed

    Ponz, Aurélie; Khatami, Ramin; Poryazova, Rositsa; Werth, Esther; Boesiger, Peter; Bassetti, Claudio L; Schwartz, Sophie

    2010-02-01

    Hypothalamic hypocretins (or orexins) regulate energy metabolism and arousal maintenance. Recent animal research suggests that hypocretins may also influence reward-related behaviors. In humans, the loss of hypocretin-containing neurons results in a major sleep-wake disorder called narcolepsy-cataplexy, which is associated with emotional disturbances. Here, we aim to test whether narcoleptic patients show an abnormal pattern of brain activity during reward processing. We used functional magnetic resonance imaging in 12 unmedicated patients with narcolepsy-cataplexy to measure the neural responses to expectancy and experience of monetary gains and losses. We statistically compared the patients' data with those obtained in a group of 12 healthy matched controls. Our results reveal that activity in the dopaminergic ventral midbrain (ventral tegmental area) was not modulated in narcolepsy-cataplexy patients during high reward expectancy (unlike controls), and that ventral striatum activity was reduced during winning. By contrast, the patients showed abnormal activity increases in the amygdala and in dorsal striatum for positive outcomes. In addition, we found that activity in the nucleus accumbens and the ventral-medial prefrontal cortex correlated with disease duration, suggesting that an alternate neural circuit could be privileged over the years to control affective responses to emotional challenges and compensate for the lack of influence from ventral midbrain regions. Our study offers a detailed picture of the distributed brain network involved during distinct stages of reward processing and shows for the first time, to our knowledge, how this network is affected in hypocretin-deficient narcoleptic patients.

  15. Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity.

    PubMed

    Matsukawa, Kanji; Ishii, Kei; Kadowaki, Akito; Liang, Nan; Ishida, Tomoko

    2012-08-15

    Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.

  16. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+)-dependence of a transient K+ current.

    PubMed

    Levic, Snezana; Lv, Ping; Yamoah, Ebenezer N

    2011-01-01

    Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+) current that regulates patterning of action potentials is I(A). This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A) are not normally classified as Ca(2+)-dependent, we demonstrate that throughout the development of chicken hair cells, I(A) is greatly reduced by acute alterations of intracellular Ca(2+). As determinants of spike timing and firing frequency, intracellular Ca(2+) buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A) are tightly regulated by intracellular Ca(2+). Such feedback mechanism between the functional expression of I(A) and intracellular Ca(2+) may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea. © 2011 Levic et al.

  17. Effects of Organophosphorus Flame Retardants on Spontaneous Activity in Neuronal Networks Grown on Microelectrode Arrays

    EPA Science Inventory

    EFFECTS OF ORGANOPHOSPHORUS FLAME RETARDANTS ON SPONTANEOUS ACTIVITY IN NEURONAL NETWORKS GROWN ON MICROELECTRODE ARRAYS TJ Shafer1, K Wallace1, WR Mundy1, M Behl2,. 1Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, USA, 2National Toxicology Program, NIEHS, RTP, NC...

  18. A Dominantly Acting Murine Allele of Mcm4 Causes Chromosomal Abnormalities and Promotes Tumorigenesis

    PubMed Central

    Bagley, Bruce N.; Keane, Thomas M.; Maklakova, Vilena I.; Marshall, Jonathon G.; Lester, Rachael A.; Cancel, Michelle M.; Paulsen, Alex R.; Bendzick, Laura E.; Been, Raha A.; Kogan, Scott C.; Cormier, Robert T.; Kendziorski, Christina; Adams, David J.; Collier, Lara S.

    2012-01-01

    Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4D573H). MCM4 is part of the heterohexameric complex of MCM2–7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4D573H to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities. PMID:23133403

  19. A dominantly acting murine allele of Mcm4 causes chromosomal abnormalities and promotes tumorigenesis.

    PubMed

    Bagley, Bruce N; Keane, Thomas M; Maklakova, Vilena I; Marshall, Jonathon G; Lester, Rachael A; Cancel, Michelle M; Paulsen, Alex R; Bendzick, Laura E; Been, Raha A; Kogan, Scott C; Cormier, Robert T; Kendziorski, Christina; Adams, David J; Collier, Lara S

    2012-01-01

    Here we report the isolation of a murine model for heritable T cell lymphoblastic leukemia/lymphoma (T-ALL) called Spontaneous dominant leukemia (Sdl). Sdl heterozygous mice develop disease with a short latency and high penetrance, while mice homozygous for the mutation die early during embryonic development. Sdl mice exhibit an increase in the frequency of micronucleated reticulocytes, and T-ALLs from Sdl mice harbor small amplifications and deletions, including activating deletions at the Notch1 locus. Using exome sequencing it was determined that Sdl mice harbor a spontaneously acquired mutation in Mcm4 (Mcm4(D573H)). MCM4 is part of the heterohexameric complex of MCM2-7 that is important for licensing of DNA origins prior to S phase and also serves as the core of the replicative helicase that unwinds DNA at replication forks. Previous studies in murine models have discovered that genetic reductions of MCM complex levels promote tumor formation by causing genomic instability. However, Sdl mice possess normal levels of Mcms, and there is no evidence for loss-of-heterozygosity at the Mcm4 locus in Sdl leukemias. Studies in Saccharomyces cerevisiae indicate that the Sdl mutation produces a biologically inactive helicase. Together, these data support a model in which chromosomal abnormalities in Sdl mice result from the ability of MCM4(D573H) to incorporate into MCM complexes and render them inactive. Our studies indicate that dominantly acting alleles of MCMs can be compatible with viability but have dramatic oncogenic consequences by causing chromosomal abnormalities.

  20. Spontaneous ordering and vortex states of active fluids in circular confinement

    NASA Astrophysics Data System (ADS)

    Theillard, Maxime; Ezhilan, Barath; Saintillan, David

    2015-11-01

    Recent experimental, theoretical and simulation studies have shown that confinement can profoundly affect self-organization in active suspensions leading to striking features such as directed fluid pumping in planar confinement, formation of steady and spontaneous vortices in radial confinement. Motivated by this, we study the dynamics in a suspension of biologically active particles confined in spherical geometries using a mean-field kinetic theory for which we developed a novel numerical solver. In the case of circular confinement, we conduct a systematic exploration of the entire parameter space and distinguish 3 broad states: no-flow, stable vortex and chaotic and several interesting sub-states. Our efficient numerical framework is also employed to study 3D effects and dynamics in more complex geometries.

  1. Malignant Transformation Potentials of Human Umbilical Cord Mesenchymal Stem Cells Both Spontaneously and via 3-Methycholanthrene Induction

    PubMed Central

    Lai, Xiulan; Liu, Sizheng; Chen, Yezeng; Zheng, Zexin; Xie, Qingdong; Maldonado, Martin; Cai, Zhiwei; Qin, Shan; Ho, Guyu; Ma, Lian

    2013-01-01

    Human umbilical cord mesenchymal stem cells (HUMSCs) are highly proliferative and can be induced to differentiate into advanced derivatives of all three germ layers. Thus, HUMSCs are considered to be a promising source for cell-targeted therapies and tissue engineering. However there are reports on spontaneous transformation of mesenchymal stem cells (MSCs) derived from human bone marrows. The capacity for HUMSCs to undergo malignant transform spontaneously or via induction by chemical carcinogens is presently unknown. Therefore, we isolated HUMSCs from 10 donors and assessed their transformation potential either spontaneously or by treating them with 3-methycholanthrene (3-MCA), a DNA-damaging carcinogen. The malignant transformation of HUMSCs in vitro was evaluated by morphological changes, proliferation rates, ability to enter cell senescence, the telomerase activity, chromosomal abnormality, and the ability to form tumors in vivo. Our studies showed that HUMSCs from all 10 donors ultimately entered senescence and did not undergo spontaneous malignant transformation. However, HUMSCs from two of the 10 donors treated with 3-MCA displayed an increased proliferation rate, failed to enter senescence, and exhibited an altered cell morphology. When these cells (tHUMSCs) were injected into immunodeficient mice, they gave rise to sarcoma-like or poorly differentiated tumors. Moreover, in contrast to HUMSCs, tHUMSCs showed a positive expression of human telomerase reverse transcriptase (hTERT) and did not exhibit a shortening of the relative telomere length during the long-term culture in vitro. Our studies demonstrate that HUMSCs are not susceptible to spontaneous malignant transformation. However, the malignant transformation could be induced by chemical carcinogen 3-MCA. PMID:24339974

  2. Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

    PubMed

    Basta, Dietmar; Götze, Romy; Gröschel, Moritz; Jansen, Sebastian; Janke, Oliver; Tzschentke, Barbara; Boyle, Patrick; Ernst, Arne

    2015-12-01

    In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the

  3. Cervical Dilatation Curves of Spontaneous Deliveries in Pregnant Japanese Females

    PubMed Central

    Inde, Yusuke; Nakai, Akihito; Sekiguchi, Atsuko; Hayashi, Masako; Takeshita, Toshiyuki

    2018-01-01

    Background: Although cervical dilatation curves are crucial for appropriate management of labor progression, abnormal labor progression and obstetric interventions were included in previous and widely-used cervical dilatation curves. We aimed to describe the cervical dilatation curves of normal labor progression in pregnant Japanese females without abnormal labor progression and obstetric interventions. Methods: We completed retrospective obstetric record reviews on 3172 pregnant Japanese females (parity = 0, n = 1047; parity = 1, n = 1083; parity ≥ 2, n = 1042), aged 20 to 39 years old at delivery, with pregravid body mass indices of less than 30. All patients underwent spontaneous deliveries with term, singleton, cephalic and live newborns of appropriate-for-gestational age birthweight, without adverse neonatal outcomes. We characterized labor progression patterns by examining the relationship between elapsed times from the full dilatation and cervical dilatation stages, and labor durations by examining the distribution of time intervals from one cervical dilatation stage, to the next, and ultimately to the full dilatation. Results: Fastest cervical changes occurred at 6 cm (primiparas) and 5 cm (multiparas) of dilatation. The 95%tile of labor progression took over 3 hours to progress from 6 cm to 7 cm (primiparas), and over 2 hours to progress from 5 cm to 6 cm (multiparas). The 5%tile of traverse time to the full dilatation, during the active phase, was less than 1 hour (primiparas) and 0.5 hours (multiparas). At the end of the active phase, no deceleration phase was observed. Conclusions: Active labor may not start until 5 cm of dilatation. At the beginning of the active phase, cervical dilatation was slower than previously described. These results may reduce opportunities for obstetric interventions during labor progression. PMID:29725244

  4. Abnormal activation of the primary somatosensory cortex in spasmodic dysphonia: an fMRI study.

    PubMed

    Simonyan, Kristina; Ludlow, Christy L

    2010-11-01

    Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD.

  5. Abnormal Activation of the Primary Somatosensory Cortex in Spasmodic Dysphonia: An fMRI Study

    PubMed Central

    Ludlow, Christy L.

    2010-01-01

    Spasmodic dysphonia (SD) is a task-specific focal dystonia of unknown pathophysiology, characterized by involuntary spasms in the laryngeal muscles during speaking. Our aim was to identify symptom-specific functional brain activation abnormalities in adductor spasmodic dysphonia (ADSD) and abductor spasmodic dysphonia (ABSD). Both SD groups showed increased activation extent in the primary sensorimotor cortex, insula, and superior temporal gyrus during symptomatic and asymptomatic tasks and decreased activation extent in the basal ganglia, thalamus, and cerebellum during asymptomatic tasks. Increased activation intensity in SD patients was found only in the primary somatosensory cortex during symptomatic voice production, which showed a tendency for correlation with ADSD symptoms. Both SD groups had lower correlation of activation intensities between the primary motor and sensory cortices and additional correlations between the basal ganglia, thalamus, and cerebellum during symptomatic and asymptomatic tasks. Compared with ADSD patients, ABSD patients had larger activation extent in the primary sensorimotor cortex and ventral thalamus during symptomatic task and in the inferior temporal cortex and cerebellum during symptomatic and asymptomatic voice production. The primary somatosensory cortex shows consistent abnormalities in activation extent, intensity, correlation with other brain regions, and symptom severity in SD patients and, therefore, may be involved in the pathophysiology of SD. PMID:20194686

  6. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

    PubMed

    Demaria, Olivier; De Gassart, Aude; Coso, Sanja; Gestermann, Nicolas; Di Domizio, Jeremy; Flatz, Lukas; Gaide, Olivier; Michielin, Olivier; Hwu, Patrick; Petrova, Tatiana V; Martinon, Fabio; Modlin, Robert L; Speiser, Daniel E; Gilliet, Michel

    2015-12-15

    Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma.

  7. Combining task-evoked and spontaneous activity to improve pre-operative brain mapping with fMRI

    PubMed Central

    Fox, Michael D.; Qian, Tianyi; Madsen, Joseph R.; Wang, Danhong; Li, Meiling; Ge, Manling; Zuo, Huan-cong; Groppe, David M.; Mehta, Ashesh D.; Hong, Bo; Liu, Hesheng

    2016-01-01

    Noninvasive localization of brain function is used to understand and treat neurological disease, exemplified by pre-operative fMRI mapping prior to neurosurgical intervention. The principal approach for generating these maps relies on brain responses evoked by a task and, despite known limitations, has dominated clinical practice for over 20 years. Recently, pre-operative fMRI mapping based on correlations in spontaneous brain activity has been demonstrated, however this approach has its own limitations and has not seen widespread clinical use. Here we show that spontaneous and task-based mapping can be performed together using the same pre-operative fMRI data, provide complimentary information relevant for functional localization, and can be combined to improve identification of eloquent motor cortex. Accuracy, sensitivity, and specificity of our approach are quantified through comparison with electrical cortical stimulation mapping in eight patients with intractable epilepsy. Broad applicability and reproducibility of our approach is demonstrated through prospective replication in an independent dataset of six patients from a different center. In both cohorts and every individual patient, we see a significant improvement in signal to noise and mapping accuracy independent of threshold, quantified using receiver operating characteristic curves. Collectively, our results suggest that modifying the processing of fMRI data to incorporate both task-based and spontaneous activity significantly improves functional localization in pre-operative patients. Because this method requires no additional scan time or modification to conventional pre-operative data acquisition protocols it could have widespread utility. PMID:26408860

  8. On-off intermittency in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hramov, Alexander; Koronovskii, Alexey A.; Midzyanovskaya, I.S.

    2006-12-15

    In the present paper we consider the on-off intermittency phenomena observed in time series of spontaneous paroxysmal activity in rats with genetic absence epilepsy. The method to register and analyze the electroencephalogram with the help of continuous wavelet transform is also suggested.

  9. Posttraumatic stress disorder and risk of spontaneous preterm birth.

    PubMed

    Shaw, Jonathan G; Asch, Steven M; Kimerling, Rachel; Frayne, Susan M; Shaw, Kate A; Phibbs, Ciaran S

    2014-12-01

    To evaluate the association between antenatal posttraumatic stress disorder (PTSD) and spontaneous preterm delivery. We identified antenatal PTSD status and spontaneous preterm delivery in a retrospective cohort of 16,334 deliveries covered by the Veterans Health Administration from 2000 to 2012. We divided mothers with PTSD into those with diagnoses present the year before delivery (active PTSD) and those only with earlier diagnoses (historical PTSD). We identified spontaneous preterm birth and potential confounders including age, race, military deployment, twins, hypertension, substance use, depression, and results of military sexual trauma screening and then performed multivariate regression to estimate adjusted odds ratio (OR) of spontaneous preterm delivery as a function of PTSD status. Of 16,334 births, 3,049 (19%) were to mothers with PTSD diagnoses, of whom 1,921 (12%) had active PTSD. Spontaneous preterm delivery was higher in those with active PTSD (9.2%, n=176) than those with historical (8.0%, n=90) or no PTSD (7.4%, n=982) before adjustment (P=.02). The association between PTSD and preterm birth persisted, when adjusting for covariates, only in those with active PTSD (adjusted OR 1.35, 95% confidence interval [CI] 1.14-1.61). Analyses adjusting for comorbid psychiatric and medical diagnoses revealed the association with active PTSD to be robust. In this cohort, containing an unprecedented number of PTSD-affected pregnancies, mothers with active PTSD were significantly more likely to suffer spontaneous preterm birth with an attributable two excess preterm births per 100 deliveries (95% CI 1-4). Posttraumatic stress disorder's health effects may extend, through birth outcomes, into the next generation.

  10. Predictive factors of spontaneous CMV DNAemia clearance in kidney transplantation.

    PubMed

    Noble, Johan; Gatault, Philippe; Sautenet, Bénédicte; Gaudy-Graffin, Catherine; Beby-Defaux, Agnes; Thierry, Antoine; Essig, Marie; Halimi, Jean-Michel; Munteanu, Eliza; Alain, Sophie; Buchler, Matthias

    Cytomegalovirus (CMV) infection occurs frequently after solid organ transplantation. Therapeutic strategies, in particular when to start a curative treatment, has not yet been defined. The purpose of this study was to assess predictive factors associated with spontaneous clearance of CMV DNAemia in kidney transplant recipients. All kidney recipients of a single center were recruited. Patients with at least one positive CMV DNAemia during the first year post transplantation were included in our analysis. Whole blood CMV PCR was performed using Abbott ® RealTime CMV, calibrated according to WHO standards and expressed in log10 IU/ml (Detection = 1.79 IU log10/ml). Post transplantation, prophylaxis (valganciclovir) was given for 3 months for CMV positive recipients (R+) and 6 months for CMV positive donors giving to seronegative recipients (D + R-). Clinical and biological symptoms attributable to CMV were collected. We defined as spontaneous CMV clearance undetectable DNAemia before the fourth follow up without treatment. Results were expressed as mean ± SD. Results were prospectively assessed in a French multicenter validation cohort. Between 05/2012 and 05/2015, 95 patients had at least one positive CMV DNAemia. Thirty-six (37.8%) had spontaneous undetectable DNAemia. Fifty-nine patients had non-spontaneous CMV clearance. ROC analysis showed that an initial CMV DNAemia <2.75 log10/IU/mL was optimal to predict CMV spontaneous clearance. On multivariate analysis, factors associated with spontaneous CMV clearance were initial PCR level lower than 2.75 log10/IU/ml (OR = 33.8, 95% CI [7.1-160.0]), and absence of CMV DNAemia increase of more than 1 log10 between two analyses (OR = 128.0, 95% CI [11.9-1368.0]). Clinical and biological abnormalities were not associated CMV DNAemia spontaneous clearance. Observations made for the principal cohort were validated in an independent cohort of 49 kidney transplanted patients. Initial standardized

  11. Sources of variation and genetic profile of spontaneous, out-of-season ovulatory activity in the Chios sheep

    PubMed Central

    Avdi, Melpomeni; Banos, Georgios; Kouttos, Athanasios; Bodin, Loys; Chemineau, Philippe

    2003-01-01

    Organising the breeding plan of a seasonally breeding species, such as sheep, presents a challenge to farmers and the industry as a whole, since both economical and biological considerations need to be carefully balanced. Understanding the breeding activity of individual animals becomes a prerequisite for a successful breeding program. This study set out to investigate the sources of variation and the genetic profile of the spontaneous, out-of-season ovulatory activity of ewes of the Chios dairy sheep breed in Greece. The definition of the trait was based on blood progesterone levels, measured before exposing the ewes to rams, which marks the onset of the usual breeding season. Data were 707 records, taken over two consecutive years, of 435 ewes kept at the Agricultural Research Station of Chalkidiki in northern Greece. When all available pedigree was included, the total number of animals involved was 1068. On average, 29% of all ewes exhibited spontaneous, out-of-season ovulatory activity, with no substantial variation between the years. Significant sources of systematic variation were the ewe age and live weight, and the month of previous lambing. Older, heavier ewes, that had lambed early the previous autumn, exhibited more frequent activity. Heritability estimates were 0.216 (± 0.084) with a linear and 0.291 with a threshold model. The latter better accounts for the categorical nature of the trait. The linear model repeatability was 0.230 (± 0.095). The results obtained in this study support the notion that spontaneous out-of-season ovulatory activity can be considered in the development of a breeding plan for the Chios sheep breed. PMID:12605851

  12. Brain activation for spontaneous and explicit false belief tasks overlaps: new fMRI evidence on belief processing and violation of expectation

    PubMed Central

    Desmet, Charlotte; Nijhof, Annabel; Wiersema, Jan R.; Brass, Marcel

    2017-01-01

    Abstract There is extensive discussion on whether spontaneous and explicit forms of ToM are based on the same cognitive/neural mechanisms or rather reflect qualitatively different processes. For the first time, we analyzed the BOLD signal for false belief processing by directly comparing spontaneous and explicit ToM task versions. In both versions, participants watched videos of a scene including an agent who acquires a true or false belief about the location of an object (belief formation phase). At the end of the movies (outcome phase), participants had to react to the presence of the object. During the belief formation phase, greater activity was found for false vs true belief trials in the right posterior parietal cortex. The ROI analysis of the right temporo-parietal junction (TPJ), confirmed this observation. Moreover, the anterior medial prefrontal cortex (aMPFC) was active during the outcome phase, being sensitive to violation of both the participant’s and agent’s expectations about the location of the object. Activity in the TPJ and aMPFC was not modulated by the spontaneous/explicit task. Overall, these data show that neural mechanisms for spontaneous and explicit ToM overlap. Interestingly, a dissociation between TPJ and aMPFC for belief tracking and outcome evaluation, respectively, was also found. PMID:27683425

  13. Flecainide-induced proarrhythmia is attributed to abnormal changes in repolarization and refractoriness in perfused guinea-pig heart.

    PubMed

    Osadchii, Oleg E

    2012-11-01

    Flecainide is nonselective Na(+) channel blocker which may also inhibit I(Kr), the rapid component of the delayed rectifier. This study was designed to explore if proarrhythmic responses to flecainide noted in cardiac patients may be partly attributed to abnormal changes in repolarization and refractoriness. Monophasic action potential duration (APD) and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated perfused guinea-pig heart preparations. Flecainide was found to prolong ventricular repolarization, with effect being greater at the left ventricular compared with the right ventricular epicardium. This change translated to reversal of the normal right ventricular-to-left ventricular transepicardial APD difference determined before drug infusion. An inverse correlation between local epicardial APD and corresponding activation time values seen at baseline was eliminated in flecainide-treated hearts, indicating the activation-to-repolarization uncoupling. Over transmural plane, flecainide produced a greater ERP lengthening at endocardium than epicardium, thus markedly increasing ERP dispersion across ventricular wall. Spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 45% of heart preparations upon flecainide infusion. In conclusion, in nonischemic guinea-pig heart, flecainide-induced proarrhythmia may be partly attributed to abnormal spatial gradients in repolarization and refractoriness and impaired transepicardial activation-to-repolarization coupling.

  14. Enhancement of antioxidant activity, α-glucosidase and α-amylase inhibitory activities by spontaneous and bacterial monoculture fermentation of Indonesian black grape juices

    NASA Astrophysics Data System (ADS)

    Frediansyah, Andri; Nurhayati, Rifa; Romadhoni, Fitrio

    2017-01-01

    This study was conducted to evaluate the in vitro antioxidant activity, α-glucosidase and α-amylase inhibitor activity of fermented black grape (Vitisvinifera) juice. In the present study black grape juice was prepared using spontaneous (SF) and monoculture fermentation (FL) of Lactobacillus plantarum FNCC 0027 and incubated for 48 h. The antioxidant capacity increased after fermentation. FL had the highest DPPH inhibition (81.32±3.45; p ≤ 0.05) compared to SF and unfermented (UF) black grape juice (75.17±1.47 and 65.63±1.02%, respectively). The pH values decreased during fermentation for both, SF and FL. M also had highest inhibition of α-glucosidase (80.15±3.23) and α-amylase (39.95±0.88). Fermentation of black grape juice using monoculture of L. plantarum has higher antioxidant activities and enzyme inhibitor effect than spontaneous and unfermented black grape juices (p ≤ 0.05). Thus fermented black grape juice may have the potential to serve as enhanced functional juice with anti-diabetic properties.

  15. Hemodynamic, ventilatory, and biochemical responses of panic patients and normal controls with sodium lactate infusion and spontaneous panic attacks.

    PubMed

    Gaffney, F A; Fenton, B J; Lane, L D; Lake, C R

    1988-01-01

    Hemodynamic, ventilatory, and biochemical variables were measured in ten healthy adults and ten panic patients during infusion of 0.5 mol/L of sodium lactate. Physical activity, fitness level, and ambulatory electrocardiograms were also recorded. Lactate infusion doubled cardiac output, increased blood lactate levels by sixfold, and produced hypernatremia, hypocalcemia, and decreased serum bicarbonate levels in both groups but raised arterial pressure only in the patients. The patients hyperventilated before and during the infusion. Physiological responses and somatic complaints with the infusion differed little between the groups, but emotional complaints were six times more frequent among the panic patients. Eight patients but no control subjects interpreted their symptoms as a panic attack. Heart rate increased with only 14 of 31 recorded spontaneous outpatient panic attacks. Sodium lactate infusions appear to produce panic by mimicking the physiology of spontaneous panic. Treatment with cardioactive agents is not indicated in the absence of cardiopulmonary or autonomic nervous system abnormalities.

  16. Prediction of heart abnormality using MLP network

    NASA Astrophysics Data System (ADS)

    Hashim, Fakroul Ridzuan; Januar, Yulni; Mat, Muhammad Hadzren; Rizman, Zairi Ismael; Awang, Mat Kamil

    2018-02-01

    Heart abnormality does not choose gender, age and races when it strikes. With no warning signs or symptoms, it can result to a sudden death of the patient. Generally, heart's irregular electrical activity is defined as heart abnormality. Via implementation of Multilayer Perceptron (MLP) network, this paper tries to develop a program that allows the detection of heart abnormality activity. Utilizing several training algorithms with Purelin activation function, an amount of heartbeat signals received through the electrocardiogram (ECG) will be employed to condition the MLP network.

  17. Spontaneous 15N Nuclear Spin Hyperpolarization in Metal-Free Activation of Parahydrogen by Molecular Tweezers

    PubMed Central

    2018-01-01

    The ability of frustrated Lewis pairs (FLPs) to activate H2 is of significant interest for metal-free catalysis. The activation of H2 is also the key element of parahydrogen-induced polarization (PHIP), one of the nuclear spin hyperpolarization techniques. It is demonstrated that o-phenylene-based ansa-aminoboranes (AABs) can produce 1H nuclear spin hyperpolarization through a reversible interaction with parahydrogen at ambient temperatures. Heteronuclei are useful in NMR and MRI as well because they have a broad chemical shift range and long relaxation times and may act as background-free labels. We report spontaneous formation of 15N hyperpolarization of the N–H site for a family of AABs. The process is efficient at the high magnetic field of an NMR magnet (7 T), and it provides up to 350-fold 15N signal enhancements. Different hyperpolarization effects are observed with various AAB structures and in a broad temperature range. Spontaneous hyperpolarization, albeit an order of magnitude weaker than that for 15N, was also observed for 11B nuclei. PMID:29401399

  18. Spaced sessions of avoidance extinction reduce spontaneous recovery and promote infralimbic cortex activation.

    PubMed

    Tapias-Espinosa, Carles; Kádár, Elisabet; Segura-Torres, Pilar

    2018-01-15

    Extinction-based therapies (EBT) are the psychological treatments of choice for certain anxiety disorders, such as post-traumatic stress disorder. However, some patients relapse and suffer spontaneous recovery (SR) of anxiety symptoms and persistence of avoidance behaviour, which underlines the need for improving EBT. In rats, recent evidence has highlighted the relevance of the temporal distribution of extinction sessions in reducing SR of auditory fear conditioning, although it has seldom been studied in procedures involving proactive avoidance responses, such as two-way active avoidance conditioning (TWAA). We examined whether the temporal distribution of two extinction sessions separated by 24h or 7days (contiguous versus spaced extinction paradigms, respectively), influences SR after 28days of a TWAA task. c-Fos expression, as a marker of neuronal activation, was also measured by immunohistochemistry 90min after the SR test in the amygdala and the medial prefrontal cortex. The temporal distribution of extinction sessions did not affect the degree of extinction learning. However, only the rats that underwent the 7-day spaced extinction paradigm maintained the level of extinction in the long term, showing no SR in TWAA. This behavioural finding was consistent with a greater number of c-Fos-labelled neurons in the infralimbic cortex in the 7-day group, and in the Lateral and Central nuclei of the amygdala in the 24-hour group. These findings show that a time-spaced extinction paradigm reduces the spontaneous recovery of active avoidance behaviour, and that this behavioural advantage appears to be related to the activation of the infralimbic cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial.

    PubMed

    Ugwumadu, Austin; Manyonda, Isaac; Reid, Fiona; Hay, Phillip

    2003-03-22

    Abnormal vaginal flora and bacterial vaginosis are associated with amplified risks of late miscarriage and spontaneous preterm delivery. We aimed to establish whether antibiotic treatment early in the second trimester might reduce these risks in a general obstetric population. We screened 6120 pregnant women attending hospital for their first antenatal visit--who were at 12-22 weeks' gestation (mean 15.6 weeks)--for bacterial vaginosis or abnormal vaginal flora. We used gram-stained slides of vaginal smears to diagnose abnormal vaginal flora or bacterial vaginosis, in accordance with Nugent's criteria. We randomly allocated 494 women with one of these signs to receive either clindamycin 300 mg or placebo orally twice daily for 5 days. Primary endpoints were spontaneous preterm delivery (birth > or =24 but <37 weeks) and late miscarriage (pregnancy loss > or =13 but <24 weeks). Analysis was intention to treat. Nine women were lost to follow-up or had elective termination. Thus, we analysed 485 women with complete outcome data. Women receiving clindamycin had significantly fewer miscarriages or preterm deliveries (13/244) than did those in the placebo group (38/241; percentage difference 10.4%, 95% CI 5.0-15.8, p=0.0003). Clindamycin also reduced adverse outcomes across the range of abnormal Nugent scores, with maximum effect in women with the highest Nugent score of 10. Treatment of asymptomatic abnormal vaginal flora and bacterial vaginosis with oral clindamycin early in the second trimester significantly reduces the rate of late miscarriage and spontaneous preterm birth in a general obstetric population.

  20. A Multiplexed Assay for Determination of Neurotoxicant Effects on Spontaneous Network Activity and Viability from Microelectrode Arrays.

    EPA Science Inventory

    Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characterize the ability of drugs, chemicals and particles to cause neurotoxicity. While effects of compounds on spontaneous network activity is easily determined by MEA recordin...

  1. Brain activation for spontaneous and explicit false belief tasks overlaps: new fMRI evidence on belief processing and violation of expectation.

    PubMed

    Bardi, Lara; Desmet, Charlotte; Nijhof, Annabel; Wiersema, Jan R; Brass, Marcel

    2017-03-01

    There is extensive discussion on whether spontaneous and explicit forms of ToM are based on the same cognitive/neural mechanisms or rather reflect qualitatively different processes. For the first time, we analyzed the BOLD signal for false belief processing by directly comparing spontaneous and explicit ToM task versions. In both versions, participants watched videos of a scene including an agent who acquires a true or false belief about the location of an object (belief formation phase). At the end of the movies (outcome phase), participants had to react to the presence of the object. During the belief formation phase, greater activity was found for false vs true belief trials in the right posterior parietal cortex. The ROI analysis of the right temporo-parietal junction (TPJ), confirmed this observation. Moreover, the anterior medial prefrontal cortex (aMPFC) was active during the outcome phase, being sensitive to violation of both the participant's and agent's expectations about the location of the object. Activity in the TPJ and aMPFC was not modulated by the spontaneous/explicit task. Overall, these data show that neural mechanisms for spontaneous and explicit ToM overlap. Interestingly, a dissociation between TPJ and aMPFC for belief tracking and outcome evaluation, respectively, was also found. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  2. Robust Long-Range Coordination of Spontaneous Neural Activity in Waking, Sleep and Anesthesia.

    PubMed

    Liu, Xiao; Yanagawa, Toru; Leopold, David A; Fujii, Naotaka; Duyn, Jeff H

    2015-09-01

    Although the emerging field of functional connectomics relies increasingly on the analysis of spontaneous fMRI signal covariation to infer the spatial fingerprint of the brain's large-scale functional networks, the nature of the underlying neuro-electrical activity remains incompletely understood. In part, this lack in understanding owes to the invasiveness of electrophysiological acquisition, the difficulty in their simultaneous recording over large cortical areas, and the absence of fully established methods for unbiased extraction of network information from these data. Here, we demonstrate a novel, data-driven approach to analyze spontaneous signal variations in electrocorticographic (ECoG) recordings from nearly entire hemispheres of macaque monkeys. Based on both broadband analysis and analysis of specific frequency bands, the ECoG signals were found to co-vary in patterns that resembled the fMRI networks reported in previous studies. The extracted patterns were robust against changes in consciousness associated with sleep and anesthesia, despite profound changes in intrinsic characteristics of the raw signals, including their spectral signatures. These results suggest that the spatial organization of large-scale brain networks results from neural activity with a broadband spectral feature and is a core aspect of the brain's physiology that does not depend on the state of consciousness. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  3. Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.

    PubMed

    Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

    2013-08-07

    There is increasing evidence that antisocial personality disorder (ASPD) stems from brain abnormalities. However, there are only a few studies investigating brain structure in ASPD. The aim of this study was to find regional coherence abnormalities in resting-state functional MRI of ASPD. Thirty-two ASPD individuals and 34 controls underwent a resting-state functional MRI scan. The regional homogeneity (ReHo) approach was used to examine whether ASPD was related to alterations in resting-state neural activity. Support vector machine discriminant analysis was used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the ASPD individuals and controls. The results showed that, compared with controls, ASPD individuals show lower ReHo in the right cerebellum posterior lobe (Crus1) and the right middle frontal gyrus, as well as higher ReHo in the right middle occipital gyrus (BA 19), left inferior temporal gyrus (BA 37), and right inferior occipital gyrus (cuneus, BA 18). All alternation regions reported a predictive accuracy above 70%. To our knowledge, this study was the first to study the change in regional activity coherence in the resting brain of ASPD individuals. These results not only elucidated the pathological mechanism of ASPD from a resting-state functional viewpoint but also showed that these alterations in ReHo may serve as potential markers for the detection of ASPD.

  4. Spontaneous action potentials and neural coding in unmyelinated axons.

    PubMed

    O'Donnell, Cian; van Rossum, Mark C W

    2015-04-01

    The voltage-gated Na and K channels in neurons are responsible for action potential generation. Because ion channels open and close in a stochastic fashion, spontaneous (ectopic) action potentials can result even in the absence of stimulation. While spontaneous action potentials have been studied in detail in single-compartment models, studies on spatially extended processes have been limited. The simulations and analysis presented here show that spontaneous rate in unmyelinated axon depends nonmonotonically on the length of the axon, that the spontaneous activity has sub-Poisson statistics, and that neural coding can be hampered by the spontaneous spikes by reducing the probability of transmitting the first spike in a train.

  5. Spontaneous activity of single neurones in the hypothalamus of rabbits during sleep and waking

    PubMed Central

    Findlay, Alan L. R.; Hayward, James N.

    1969-01-01

    1. A method is described for recording from single cells in the hypothalamus of unanaesthetized freely moving rabbits. Behaviour, bodily movement, skin and brain temperatures and e.e.g. were monitored. 2. Patterns of unit firing during slow sleep, paradoxical sleep and waking were studied in several regions of the hypothalamus, thalamus and in the septum. 3. Of the 144 cells analysed from waking to slow sleep, fifty-six (39%) decreased mean firing rates, thirty (21%) increased spike discharges and fifty-eight (40%) showed no marked change. Dorsal hypothalamic and massa intermedia thalamic cells fired in brief high frequency clusters during slow sleep with a characteristic `bimodal' interspike interval histogram. Waking and paradoxical sleep abolished these cluster discharges with a concomitant change to an `asymmetric' histogram. 4. Of the thirty-two cells observed during the three states of waking, slow sleep and paradoxical sleep, a majority (twenty-five or 78%) showed their highest rates of spontaneous discharge during paradoxical sleep. Discharge rates of cells sometimes changed in the course of paradoxical sleep according to the presence or absence of phasic events such as myoclonic motor activity. Two hypothalmic cells were almost totally arrested during paradoxical sleep. 5. Analysis of unit firing rates during spontaneous rises in brain temperature during waking and paradoxical sleep revealed that a majority of the neurones (22/24) changed their discharge rates in relation to behaviour rather than to brain temperature. Two cells did appear to respond specifically to the central thermal stimulus. 6. Hypothalamic cells do not behave as a homogeneous population in relation to changes in the state of arousal of the rabbit. Spontaneous changes in cell discharge related to sleep-waking behaviour must be considered in any interpretation of hypothalamic unit activity as related to neuroendocrine or autonomic mechanisms. PMID:4304342

  6. Substance-P antagonists: effect on spontaneous and drug-induced locomotor activity in the rat.

    PubMed

    Elliott, P J; Iversen, S D

    1987-05-01

    The substance P (SP) antagonists (D-Pro4, D-Trp7,9, Leu11) SP(4-11), (D-Pro4, D-Trp7,9, Phe11)SP(4-11) and (D-Pro4, D-Trp7,9,10, Leu11) SP (4-11) were infused into the lateral ventricles (i.c.v.) and their effects on spontaneous and drug-induced locomotor activity were investigated. The drug DiMeC7, the stable substance P agonist, was used to stimulate locomotor activity because of its prolonged action. Only (D-Pro4, D-Trp7,9,10) SP (4-11) was found to attenuate the drug-induced increases in motor activity, indicating that it is a substance P antagonist with activity in the CNS.

  7. Salicylate-induced changes in spontaneous activity of single units in the inferior colliculus of the guinea pig.

    PubMed

    Jastreboff, P J; Sasaki, C T

    1986-11-01

    Changes in spontaneous neuronal activity of the inferior colliculus in albino guinea pigs before and after administration of sodium salicylate were analyzed. Animals were anesthetized with pentobarbital, and two microelectrodes separated by a few hundred microns were driven through the inferior colliculus. After collecting a sufficiently large sample of cells, sodium salicylate (450 mg/kg) was injected i.p. and recordings again made 2 h after the injection. Comparison of spontaneous activity recorded before and after salicylate administration revealed highly statistically significant differences (p less than 0.001). After salicylate, the mean rate of the cell population increased from 29 to 83 Hz and the median from 26 to 74 Hz. Control experiments in which sodium salicylate was replaced by saline injection revealed no statistically significant differences in cell discharges. Recordings made during the same experiments from lobulus V of the cerebellar vermis revealed no changes in response to salicylate. The observed changes in single-unit activity due to salicylate administration may represent the first systematic evidence of a tinnituslike phenomenon in animals.

  8. Abnormal brain activation during directed forgetting of negative memory in depressed patients.

    PubMed

    Yang, Wenjing; Chen, Qunlin; Liu, Peiduo; Cheng, Hongsheng; Cui, Qian; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2016-01-15

    The frequent occurrence of uncontrollable negative thoughts and memories is a troubling aspect of depression. Thus, knowledge on the mechanism underlying intentional forgetting of these thoughts and memories is crucial to develop an effective emotion regulation strategy for depressed individuals. Behavioral studies have demonstrated that depressed participants cannot intentionally forget negative memories. However, the neural mechanism underlying this process remains unclear. In this study, participants completed the directed forgetting task in which they were instructed to remember or forget neutral or negative words. Standard univariate analysis based on the General Linear Model showed that the depressed participants have higher activation in the inferior frontal gyrus (IFG), superior frontal gyrus (SFG), superior parietal gyrus (SPG), and inferior temporal gyrus (ITG) than the healthy individuals. The results indicated that depressed participants recruited more frontal and parietal inhibitory control resources to inhibit the TBF items, but the attempt still failed because of negative bias. We also used the Support Vector Machine to perform multivariate pattern classification based on the brain activation during directed forgetting. The pattern of brain activity in directed forgetting of negative words allowed correct group classification with an overall accuracy of 75% (P=0.012). The brain regions which are critical for this discrimination showed abnormal activation when depressed participants were attempting to forget negative words. These results indicated that the abnormal neural circuitry when depressed individuals tried to forget the negative words might provide neurobiological markers for depression. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Spontaneous long-range calcium waves in developing butterfly wings.

    PubMed

    Ohno, Yoshikazu; Otaki, Joji M

    2015-03-25

    Butterfly wing color patterns emerge as the result of a regular arrangement of scales produced by epithelial scale cells at the pupal stage. These color patterns and scale arrangements are coordinated throughout the wing. However, the mechanism by which the development of scale cells is controlled across the entire wing remains elusive. In the present study, we used pupal wings of the blue pansy butterfly, Junonia orithya, which has distinct eyespots, to examine the possible involvement of Ca(2+) waves in wing development. Here, we demonstrate that the developing pupal wing tissue of the blue pansy butterfly displayed spontaneous low-frequency Ca(2+) waves in vivo that propagated slowly over long distances. Some waves appeared to be released from the immediate peripheries of the prospective eyespot and discal spot, though it was often difficult to identify the specific origins of these waves. Physical damage, which is known to induce ectopic eyespots, led to the radiation of Ca(2+) waves from the immediate periphery of the damaged site. Thapsigargin, which is a specific inhibitor of Ca(2+)-ATPases in the endoplasmic reticulum, induced an acute increase in cytoplasmic Ca(2+) levels and halted the spontaneous Ca(2+) waves. Additionally, thapsigargin-treated wings showed incomplete scale development as well as other scale and color pattern abnormalities. We identified a novel form of Ca(2+) waves, spontaneous low-frequency slow waves, which travel over exceptionally long distances. Our results suggest that spontaneous Ca(2+) waves play a critical role in the coordinated development of scale arrangements and possibly in color pattern formation in butterflies.

  10. Analysis of spontaneous MEG activity in mild cognitive impairment and Alzheimer's disease using spectral entropies and statistical complexity measures

    NASA Astrophysics Data System (ADS)

    Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; García, María; Fernández, Alberto; Hornero, Roberto

    2012-06-01

    Alzheimer's disease (AD) is the most common cause of dementia. Over the last few years, a considerable effort has been devoted to exploring new biomarkers. Nevertheless, a better understanding of brain dynamics is still required to optimize therapeutic strategies. In this regard, the characterization of mild cognitive impairment (MCI) is crucial, due to the high conversion rate from MCI to AD. However, only a few studies have focused on the analysis of magnetoencephalographic (MEG) rhythms to characterize AD and MCI. In this study, we assess the ability of several parameters derived from information theory to describe spontaneous MEG activity from 36 AD patients, 18 MCI subjects and 26 controls. Three entropies (Shannon, Tsallis and Rényi entropies), one disequilibrium measure (based on Euclidean distance ED) and three statistical complexities (based on Lopez Ruiz-Mancini-Calbet complexity LMC) were used to estimate the irregularity and statistical complexity of MEG activity. Statistically significant differences between AD patients and controls were obtained with all parameters (p < 0.01). In addition, statistically significant differences between MCI subjects and controls were achieved by ED and LMC (p < 0.05). In order to assess the diagnostic ability of the parameters, a linear discriminant analysis with a leave-one-out cross-validation procedure was applied. The accuracies reached 83.9% and 65.9% to discriminate AD and MCI subjects from controls, respectively. Our findings suggest that MCI subjects exhibit an intermediate pattern of abnormalities between normal aging and AD. Furthermore, the proposed parameters provide a new description of brain dynamics in AD and MCI.

  11. Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

    2014-01-01

    Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

  12. Spontaneous Fission

    DOE R&D Accomplishments Database

    Segre, Emilio

    1950-11-22

    The first attempt to discover spontaneous fission in uranium was made by [Willard] Libby, who, however, failed to detect it on account of the smallness of effect. In 1940, [K. A.] Petrzhak and [G. N.] Flerov, using more sensitive methods, discovered spontaneous fission in uranium and gave some rough estimates of the spontaneous fission decay constant of this substance. Subsequently, extensive experimental work on the subject has been performed by several investigators and will be quoted in the various sections. [N.] Bohr and [A.] Wheeler have given a theory of the effect based on the usual ideas of penetration of potential barriers. On this project spontaneous fission has been studied for the past several years in an effort to obtain a complete picture of the phenomenon. For this purpose the spontaneous fission decay constants {lambda} have been measured for separated isotopes of the heavy elements wherever possible. Moreover, the number {nu} of neutrons emitted per fission has been measured wherever feasible, and other characteristics of the spontaneous fission process have been studied. This report summarizes the spontaneous fission work done at Los Alamos up to January 1, 1945. A chronological record of the work is contained in the Los Alamos monthly reports.

  13. Abnormal functional connectivity density in children with anisometropic amblyopia at resting-state.

    PubMed

    Wang, Tianyue; Li, Qian; Guo, Mingxia; Peng, Yanmin; Li, Qingji; Qin, Wen; Yu, Chunshui

    2014-05-14

    Amblyopia is a developmental disorder resulting from anomalous binocular visual input in early life. Task-based neuroimaging studies have widely investigated cortical functional impairments in amblyopia, but changes in spontaneous neuronal functional activities in amblyopia remain largely unknown. In the present study, functional connectivity density (FCD) mapping, an ultrafast data-driven method based on fMRI, was applied for the first time to investigate changes in cortical functional connectivities in amblyopia during the resting-state. We quantified and compared both short- and long-range FCD in both the brains of children with anisometropic amblyopia (AAC) and normal sighted children (NSC). In contrast to the NSC, the AAC showed significantly decreased short-range FCD in the inferior temporal/fusiform gyri, parieto-occipital and rostrolateral prefrontal cortices, as well as decreased long-range FCD in the premotor cortex, dorsal inferior parietal lobule, frontal-insular and dorsal prefrontal cortices. Furthermore, most regions with reduced long-range FCD in the AAC showed decreased functional connectivity with occipital and posterior parietal cortices in the AAC. The results suggest that chronically poor visual input in amblyopia not only impairs the brain's short-range functional connections in visual pathways and in the frontal cortex, which is important for cognitive control, but also affects long-range functional connections among the visual areas, posterior parietal and frontal cortices that subserve visuomotor and visual-guided actions, visuospatial attention modulation and the integration of salient information. This study provides evidence for abnormal spontaneous brain activities in amblyopia. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYS

    EPA Science Inventory

    AbstractTITLE: A MULTIPLEXED ASSAY FOR DETERMINATION OF NEUROTOXICANT EFFECTS ON SPONTANEOUS NETWORK ACTIVITY AND CELL VIABILITY FROM MICROELECTRODE ARRAYSABSTRACT BODY: Microelectrode array (MEA) recordings are increasingly being used as an in vitro method to detect and characte...

  15. Urothelial/lamina propria spontaneous activity and the role of M3 muscarinic receptors in mediating rate responses to stretch and carbachol.

    PubMed

    Moro, Christian; Uchiyama, Jumpei; Chess-Williams, Russ

    2011-12-01

    To investigate the effects of tissue stretch and muscarinic receptor stimulation on the spontaneous activity of the urothelium/lamina propria and identify the specific receptor subtype mediating these responses. Isolated strips of porcine urothelium with lamina propria were set up for in vitro recording of contractile activity. Muscarinic receptor subtype-selective antagonists were used to identify the receptors influencing the contractile rate responses to stretch and stimulation with carbachol. Isolated strips of urothelium with lamina propria developed spontaneous contractions (3.7 cycles/min) that were unaffected by tetrodotoxin, Nω-nitro-L-arginine, or indomethacin. Carbachol (1 μM) increased the spontaneous contractile rate of these tissue strips by 122% ± 27% (P < .001). These responses were significantly depressed in the presence of the M3-selective muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine methiodide (10-30 nM) but were not affected by the M1-selective antagonist pirenzepine (30-100 nM) or the M2-selective antagonist methoctramine (0.1-1 μM). Stretching of the tissue also caused an increase in the spontaneous contractile rate, and these responses were abolished by atropine (1 μM) and low concentrations of 4-diphenylacetoxy-N-methylpiperidine methiodide (10 nM). Darifenacin, oxybutynin, tolterodine, and solifenacin (1 μM) all significantly depressed the frequency responses to carbachol (1 μM). The urothelium with the lamina propria exhibits a spontaneous contractile activity that is increased during stretch. The mechanism appears to involve endogenous acetylcholine release acting on M3 muscarinic receptors. Anticholinergic drugs used clinically depress the responses of these tissues, and this mechanism might represent an additional site of action for these drugs in the treatment of bladder overactivity. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Active magneto-optical control of spontaneous emission in graphene

    DOE PAGES

    Kort-Kamp, W. J. M.; Amorim, B.; Bastos, G.; ...

    2015-11-13

    In this study, we investigate the spontaneous emission rate of a two-level quantum emitter near a graphene-coated substrate under the influence of an external magnetic field or strain induced pseudomagnetic field. We demonstrate that the application of the magnetic field can substantially increase or decrease the decay rate. We show that a suppression as large as 99% in the Purcell factor is achieved even for moderate magnetic fields. The emitter's lifetime is a discontinuous function of |B|, which is a direct consequence of the occurrence of discrete Landau levels in graphene. We demonstrate that, in the near-field regime, the magneticmore » field enables an unprecedented control of the decay pathways into which the photon/polariton can be emitted. Our findings strongly suggest that a magnetic field could act as an efficient agent for on-demand, active control of light-matter interactions in graphene at the quantum level.« less

  17. Hydrodynamic interaction induced spontaneous rotation of coupled active filaments.

    PubMed

    Jiang, Huijun; Hou, Zhonghuai

    2014-12-14

    We investigate the coupled dynamics of active filaments with long range hydrodynamic interactions (HI). Remarkably, we find that filaments can rotate spontaneously under the same conditions in which a single filament alone can only move in translation. Detailed analysis reveals that the emergence of coupled rotation originates from an asymmetric flow field associated with HI which breaks the symmetry of translational motion when filaments approach. The breaking is then further stabilized by HI to form self-sustained coupled rotation. Intensive simulations show that coupled rotation forms easily when one filament tends to collide with the front-half of the other. For head-to-tail approaching, we observe another interesting HI-induced coupled motion, where filaments move together in the form of one following the other. Moreover, the radius of coupled rotation increases exponentially as the rigidity of the filament increases, which suggests that HI are also important for the alignment of rigid-rod-like filaments which has been assumed to be solely a consequence of direct collisions.

  18. Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

    PubMed Central

    Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

    2012-01-01

    We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

  19. An assessment of the pattern of spontaneous eyeblink activity under the influence of topical ocular anaesthesia.

    PubMed

    Naase, Taher; Doughty, Michael J; Button, Norman F

    2005-04-01

    To determine whether there is a change in the pattern of human eyeblink events under topical ocular anaesthesia. Forty male subjects, aged between 19 and 52 years and with no significant ocular surface disease, were recruited. Their spontaneous eyeblink activity, in primary eye gaze position and in silence, was recorded for 5-min periods, before and after instillation of benoxinate 0.4% eyedrops. The surface anaesthesia was confirmed by aesthesiometry. The spontaneous eyeblink rate (SEBR) decreased from 9.1+/-4.0 blinks/min to an average of 5.7+/-3.3 blinks/min, with 37 subjects showing a decreased eyeblink rate under anaesthesia. Three blink patterns were observed before anaesthesia (symmetrical, J-type and I-type) and these were essentially unchanged under anaesthesia. These studies confirm that the SEBR is usually reduced under surface anaesthesia (so is sensitive to exogenous control) but the pattern of the eyeblink activity is unchanged (so is less sensitive to exogenous control). The removal of exogenous stimuli by anaesthesia does not shift the eyeblink pattern to a single type, so indicates endogenous control.

  20. Transcatheter Arterial Embolization for Spontaneous Rupture of the Omental Artery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matsumoto, Tomohiro, E-mail: t-matsu@koto.kpu-m.ac.jp; Yamagami, Takuji; Morishita, Hiroyuki

    We encountered a rare case of spontaneous rupture of the omental artery. A 25-year-old man without any episode of abdominal trauma or bleeding disorders came to the emergency unit with left upper abdominal pain. Hematoma with extravasation of the greater omentum and a hemoperitoneum was confirmed on abdominal contrast-enhanced computed tomography. Bleeding from the omental artery was suspected based on these findings. Transcatheter arterial embolization was successfully performed after extravasation of the omental artery, which arises from the left gastroepiploic artery, was confirmed on arteriography. Partial ometectomy was performed 10 days after transcatheter arterial embolization, revealing that the hematoma measuredmore » 10 cm in diameter in the greater omentum. Pathological examination showed rupture of the branch of an omental artery without abnormal findings, such as an aneurysm or neoplasm. Thus, we diagnosed him with spontaneous rupture of the omental artery. The patient recovered and was discharged from the hospital 10 days after the surgery, with a favorable postoperative course.« less

  1. Multichannel Detrended Fluctuation Analysis Reveals Synchronized Patterns of Spontaneous Spinal Activity in Anesthetized Cats

    PubMed Central

    Rodríguez, Erika E.; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A.; Jiménez, Ismael; Rudomín, Pablo

    2011-01-01

    The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA- mean = 1.040.09) or simultaneously from several lumbar segments (mDFA- mean = 1.010.06), where  = 0.5 indicates randomness while 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA- = 0.992 as compared to initial conditions mDFA- = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA- = 0.924). In contrast to the classical methods, such as correlation

  2. Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex

    PubMed Central

    Nir, Yuval; Mukamel, Roy; Dinstein, Ilan; Privman, Eran; Harel, Michal; Fisch, Lior; Gelbard-Sagiv, Hagar; Kipervasser, Svetlana; Andelman, Fani; Neufeld, Miri Y; Kramer, Uri; Arieli, Amos; Fried, Itzhak; Malach, Rafael

    2009-01-01

    Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40–100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex. PMID:19160509

  3. Abnormal neuronal activity in Tourette syndrome and its modulation using deep brain stimulation

    PubMed Central

    Israelashvili, Michal; Loewenstern, Yocheved

    2015-01-01

    Tourette syndrome (TS) is a common childhood-onset disorder characterized by motor and vocal tics that are typically accompanied by a multitude of comorbid symptoms. Pharmacological treatment options are limited, which has led to the exploration of deep brain stimulation (DBS) as a possible treatment for severe cases. Multiple lines of evidence have linked TS with abnormalities in the motor and limbic cortico-basal ganglia (CBG) pathways. Neurophysiological data have only recently started to slowly accumulate from multiple sources: noninvasive imaging and electrophysiological techniques, invasive electrophysiological recordings in TS patients undergoing DBS implantation surgery, and animal models of the disorder. These converging sources point to system-level physiological changes throughout the CBG pathway, including both general altered baseline neuronal activity patterns and specific tic-related activity. DBS has been applied to different regions along the motor and limbic pathways, primarily to the globus pallidus internus, thalamic nuclei, and nucleus accumbens. In line with the findings that also draw on the more abundant application of DBS to Parkinson's disease, this stimulation is assumed to result in changes in the neuronal firing patterns and the passage of information through the stimulated nuclei. We present an overview of recent experimental findings on abnormal neuronal activity associated with TS and the changes in this activity following DBS. These findings are then discussed in the context of current models of CBG function in the normal state, during TS, and finally in the wider context of DBS in CBG-related disorders. PMID:25925326

  4. Spontaneous autoimmune reactions against pancreatic islets in mouse strains with generalized autoimmune disease.

    PubMed

    Kolb, H; Freytag, G; Kiesel, U; Kolb-Bachofen, V

    1980-09-01

    The spontaneously autoimmune mouse strains NZB, NZB X NZW, MRL and BXSB have been examined for signs of autoimmune reactions against islet cells. Between 15 and 55 animals of each strain were tested. Infiltrates of lymphocytes and fibroblasts into pancreatic islets were found in more than 80% of NZB mice, in about 50% of MRL and NZB X NZW mice, and in less than 20% of BXSB mice. Infiltrates were not found in the exocrine portion of pancrea. All NZB mice had abnormal glucose tolerance. In the three other strains between 20 and 50% of animals had abnormal glucose tolerance. All mice had fasting normoglycaemia. The lesions in NZB mice were studied in more detail. It was found by ultrastructural analysis that in young mice pancreatic infiltrates consisted of lymphocytes and fibroblasts. Single lymphocytes were also seen outside the main infiltration area. After 2 to 5 months of age another type of infiltrate, consisting of lymphocytes and macrophages was observed. B-cell destruction by lymphocytes was apparent in both young and adult NZB mice. It is concluded that cellular autoimmune reactions against pancreatic islets may occur spontaneously as a consequence of immunological disorders in NZB, NZB X NZW and MRL mice.

  5. Identification of abnormal motor cortex activation patterns in children with cerebral palsy by functional near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Khan, Bilal; Tian, Fenghua; Behbehani, Khosrow; Romero, Mario I.; Delgado, Mauricio R.; Clegg, Nancy J.; Smith, Linsley; Reid, Dahlia; Liu, Hanli; Alexandrakis, George

    2010-05-01

    We demonstrate the utility of functional near-infrared spectroscopy (fNIRS) as a tool for physicians to study cortical plasticity in children with cerebral palsy (CP). Motor cortex activation patterns were studied in five healthy children and five children with CP (8.4+/-2.3 years old in both groups) performing a finger-tapping protocol. Spatial (distance from center and area difference) and temporal (duration and time-to-peak) image metrics are proposed as potential biomarkers for differentiating abnormal cortical activation in children with CP from healthy pediatric controls. In addition, a similarity image-analysis concept is presented that unveils areas that have similar activation patterns as that of the maximum activation area, but are not discernible by visual inspection of standard activation images. Metrics derived from the images presenting areas of similarity are shown to be sensitive identifiers of abnormal activation patterns in children with CP. Importantly, the proposed similarity concept and related metrics may be applicable to other studies for the identification of cortical activation patterns by fNIRS.

  6. Rho/Rho kinase and phosphoinositide 3-kinase are parallel pathways in the development of spontaneous arterial tone in deoxycorticosterone acetate-salt hypertension.

    PubMed

    Wehrwein, Erica A; Northcott, Carrie A; Loberg, Robert D; Watts, Stephanie W

    2004-06-01

    Hypertension is characterized by abnormal vascular contractility and function. Arteries from deoxycorticosterone acetate (DOCA)-salt hypertensive rats develop spontaneous tone that is not observed in arteries from normotensive rats. Inhibition of phosphoinositide 3-kinase (PI3-kinase) by 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) reduces spontaneous tone development. The Rho/Rho-kinase pathway has been suggested to play a role in hypertension and may be dependent on PI3-kinase activity. We hypothesized that Rhokinase is involved in spontaneous tone development and that Rho/Rho-kinase is a downstream effector of PI3-kinase. Using endothelium-denuded aortic strips in isolated tissue bath, we demonstrated that (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) (Y27632) (1 microM), a Rho-kinase inhibitor, significantly reduced spontaneous tone in the DOCA aorta but that it did not affect sham aorta basal tone (DOCA 63.5 +/- 15.9 versus sham 1.2 +/- 0.4 total change in percentage of phenylephrine contraction). We examined the interaction between the PI3-kinase and Rho pathways by observing the effects of LY294002 on a Rhokinase effector, myosin phosphatase (MYPT), and Y27632 on a PI3-kinase effector, Akt, using Western blot analysis. Inhibition of PI3-kinase reduced spontaneous tone, but it had no effect on the phosphorylation status of MYPT, indicating that PI3-kinase is not a downstream effector of Rho/Rho-kinase. These data indicate that there is little interaction between the Rho/Rhokinase and PI3-kinase pathways in the DOCA-salt aorta, and the two pathways seem to operate in parallel in supporting spontaneous arterial tone. These data reflect spontaneous tone only and do not rule out the possibility of interaction between these pathways in agonist-stimulated tone.

  7. Spontaneous activity in the waiting brain: a marker of impulsive choice in attention-deficit/hyperactivity disorder?

    PubMed

    Hsu, Chia-Fen; Benikos, Nicholas; Sonuga-Barke, Edmund J S

    2015-04-01

    Spontaneous very low frequency oscillations (VLFO), seen in the resting brain, are attenuated when individuals are working on attention demanding tasks or waiting for rewards (Hsu et al., 2013). Individuals with attention-deficit/hyperactivity disorder (ADHD) display excess VLFO when working on attention tasks. They also have difficulty waiting for rewards. Here we examined the waiting brain signature in ADHD and its association with impulsive choice. DC-EEG from 21 children with ADHD and 21 controls (9-15 years) were collected under four conditions: (i) resting; (ii) choosing to wait; (iii) being "forced" to wait; and (iv) working on a reaction time task. A questionnaire measured two components of impulsive choice. Significant VLFO reductions were observed in controls within anterior brain regions in both working and waiting conditions. Individuals with ADHD showed VLFO attenuation while working but to a reduced level and none at all when waiting. A closer inspection revealed an increase of VLFO activity in temporal regions during waiting. Excess VLFO activity during waiting was associated with parents' ratings of temporal discounting and delay aversion. The results highlight the potential role for waiting-related spontaneous neural activity in the pathophysiology of impulsive decision-making of ADHD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Spontaneous intracranial hypotension.

    PubMed

    Gordon, Neil

    2009-12-01

    Since the introduction of magnetic resonance imaging (MRI), spontaneous intracranial hypotension has been diagnosed much more frequently. The aim of this review is to discuss the symptoms and signs of the condition, in particular the characteristics of the associated headache, with sudden onset after sitting or standing, so that it can be included under the rubric of 'thunderclap headache'. This type of headache, like post lumbar puncture headaches, may be caused by cerebral vasodilatation and exacerbated by lowered pressure of the cerebrospinal fluid (CSF). Other symptoms include neck stiffness, nausea, vomiting, vertigo, tinnitus, deafness, and cognitive abnormalities. The clinical picture can sometimes mimic frontotemporal dementia, and the behaviour of some patients can sometimes be described as hypoactive-hypoalert, with somnolence, impaired attention, and stereotyped motor activity. Sagging of the brain, caused by leakeage of the CSF, can cause lesions in the brainstem with stupor, gaze palsies, and cranial nerve palsies. The condition can be a risk factor for cerebral venous thrombosis because of slowing of the blood flow and distortion of the blood vessels. The clinical picture may well suggest the diagnosis, but the headache may possibly indicate a subarachnoid haemorrhage. However, MRI will help to confirm the diagnosis and to localize the site of the CSF leak. MRI myelograms are of particular value, but if they are equivocal a computed tomography myelogram should be performed. The leakage of CSF is due to a tear in the dura, most frequently where the spinal roots leave the subarachnoid space. If this does not heal with bedrest, an epidural blood patch or a percutaneous injection of fibrin glue may be needed. More information is required on long-term follow-up.

  9. Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.

    PubMed

    Albillos, Agustín; Hera Ad, Antonio de la; Reyes, Eduardo; Monserrat, Jorge; Muñoz, Leticia; Nieto, Mónica; Prieto, Alfredo; Sanz, Eva; Alvarez-Mon, Melchor

    2004-04-01

    To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis. Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo. Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis. In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.

  10. Spontaneous pneumocephalus after commercial air travel complicated by meningitis.

    PubMed

    Javan, Ramin; Duszak, Richard; Eisenberg, Alan D; Eggers, Frank M

    2011-12-01

    Pneumocephalus usually results from trauma, infection, neoplasm, or iatrogenic causes. Barotrauma-induced spontaneous pneumocephalus is extremely rare, usually seen in divers or occassionally with air travel. We report a case of a 61-yr-old female presenting with confusion, fever, and respiratory failure one day after developing sudden nausea, vomiting, and headache during descent on a commercial airliner. Pneumocephalus and meningitis were present on admission. Sinus computed tomography (CT) showed pansinusitis and a tiny bone defect in the posterior wall of the right sphenoid sinus, through which a cisternogram later showed free communication with the prepontine cistern. An orbital CT 2 yr earlier after a fall showed the bone defect, with no other areas of abnormality or fracture. After repair of defects by otolaryngology and appropriate antibiotics, she did well and was eventually discharged. Changes in aircraft cabin pressure likely resulted in rupture of dura and arachnoid layers beneath the pre-existing bony defect, predisposed by existing sinus disease. The pathophysiology, implications, and potential sources of spontaneous pneumocephalus, as well as risks of postcraniotomy and post-trauma air-travel, are discussed.

  11. Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

    PubMed Central

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  12. Memory in a fractional-order cardiomyocyte model alters properties of alternans and spontaneous activity

    NASA Astrophysics Data System (ADS)

    Comlekoglu, T.; Weinberg, S. H.

    2017-09-01

    Cardiac memory is the dependence of electrical activity on the prior history of one or more system state variables, including transmembrane potential (Vm), ionic current gating, and ion concentrations. While prior work has represented memory either phenomenologically or with biophysical detail, in this study, we consider an intermediate approach of a minimal three-variable cardiomyocyte model, modified with fractional-order dynamics, i.e., a differential equation of order between 0 and 1, to account for history-dependence. Memory is represented via both capacitive memory, due to fractional-order Vm dynamics, that arises due to non-ideal behavior of membrane capacitance; and ionic current gating memory, due to fractional-order gating variable dynamics, that arises due to gating history-dependence. We perform simulations for varying Vm and gating variable fractional-orders and pacing cycle length and measure action potential duration (APD) and incidence of alternans, loss of capture, and spontaneous activity. In the absence of ionic current gating memory, we find that capacitive memory, i.e., decreased Vm fractional-order, typically shortens APD, suppresses alternans, and decreases the minimum cycle length (MCL) for loss of capture. However, in the presence of ionic current gating memory, capacitive memory can prolong APD, promote alternans, and increase MCL. Further, we find that reduced Vm fractional order (typically less than 0.75) can drive phase 4 depolarizations that promote spontaneous activity. Collectively, our results demonstrate that memory reproduced by a fractional-order model can play a role in alternans formation and pacemaking, and in general, can greatly increase the range of electrophysiological characteristics exhibited by a minimal model.

  13. Do clinical data and human papilloma virus genotype influence spontaneous regression in grade I cervical intraepithelial neoplasia?

    PubMed

    Cortés-Alaguero, Caterina; González-Mirasol, Esteban; Morales-Roselló, José; Poblet-Martinez, Enrique

    2017-03-15

    To determine whether medical history, clinical examination and human papilloma virus (HPV) genotype influence spontaneous regression in cervical intraepithelial neoplasia grade I (CIN-I). We retrospectively evaluated 232 women who were histologically diagnosed as have CIN-I by means of Kaplan-Meier curves, the pattern of spontaneous regression according to the medical history, clinical examination, and HPV genotype. Spontaneous regression occurred in most patients and was influenced by the presence of multiple HPV genotypes but not by the HPV genotype itself. In addition, regression frequency was diminished when more than 50% of the cervix surface was affected or when an abnormal cytology was present at the beginning of follow-up. The frequency of regression in CIN-I is high, making long-term follow-up and conservative management advisable. Data from clinical examination and HPV genotyping might help to anticipate which lesions will regress.

  14. Spontaneous calcium transients in the immature adult-born neurons of the olfactory bulb.

    PubMed

    Maslyukov, Anatoliy; Li, Kaizhen; Su, Xin; Kovalchuk, Yury; Garaschuk, Olga

    2018-06-06

    Spontaneous neuronal activity and concomitant intracellular Ca 2+ signaling are abundant during early perinatal development and are well known for their key role in neuronal proliferation, migration, differentiation and wiring. However, much less is known about the in vivo patterns of spontaneous Ca 2+ signaling in immature adult-born cells. Here, by using two-photon Ca 2+ imaging, we analyzed spontaneous in vivo Ca 2+ signaling in adult-born juxtaglomerular cells of the mouse olfactory bulb over the time period of 5 weeks, from the day of their arrival in the glomerular layer till their stable integration into the preexisting neural network. We show that spontaneous Ca 2+ transients are ubiquitously present in adult-born cells right after their arrival, require activation of voltage-gated Na + channels and are little sensitive to isoflurane anesthesia. Interestingly, several parameters of this spontaneous activity, such as the area under the curve, the time spent in the active state as well as the fraction of continuously active cells show a bell-shaped dependence on cell's age, all peaking in 3-4 weeks old cells. This data firmly document the in vivo presence of spontaneous Ca 2+ signaling during the layer-specific maturation of adult-born neurons in the olfactory bulb and motivate further analyses of the functional role(s) of this activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Somatostatin-28 modulates prepulse inhibition of the acoustic startle response, reward processes and spontaneous locomotor activity in rats

    PubMed Central

    Semenova, Svetlana; Hoyer, Daniel; Geyer, Mark A.; Markou, Athina

    2011-01-01

    Somatostatins have been shown to be involved in the pathophysiology of motor and affective disorders, as well as psychiatry disorders, including schizophrenia. We hypothesized that in addition to motor function, somatostatin may be involved in somatosensory gating and reward processes that have been shown to be dysregulated in schizophrenia. Accordingly, we evaluated the effects of intracerebroventricular administration of somatostatin-28 on spontaneous locomotor and exploratory behavior measured in a behavioral pattern monitor, sensorimotor gating, prepulse inhibition (PPI) of the acoustic startle reflex, and brain reward function (measured in a discrete trial intracranial self-stimulation procedure) in rats. Somatostatin-28 decreased spontaneous locomotor activity during the first 10 min of a 60 min testing session with no apparent changes in the exploratory activity of rats. The highest somatostatin-28 dose (10 μg/5 μl/side) induced PPI deficits with no effect on the acoustic startle response or startle response habituation. The somatostatin-induced PPI deficit was partially reversed by administration of SRA-880, a selective somatostatin 1 (sst1) receptor antagonist. Somatostatin-28 also induced elevations in brain reward thresholds, reflecting an anhedonic-like state. SRA-880 had no effect on brain reward function under baseline conditions. Altogether these findings suggest that somatostatin-28 modulates PPI and brain reward function but does not have a robust effect on spontaneous exploratory activity. Thus, increases in somatostatin transmission may represent one of the neurochemical mechanisms underlying anhedonia, one of the negative symptoms of schizophrenia, and sensorimotor gating deficits associated with cognitive impairments in schizophrenia patients. PMID:20537385

  16. Anti-nerve growth factor therapy increases spontaneous day/night activity in mice with orthopedic surgery-induced pain.

    PubMed

    Majuta, Lisa A; Guedon, Jean-Marc G; Mitchell, Stefanie A T; Ossipov, Michael H; Mantyh, Patrick W

    2017-04-01

    Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are 2 of the most common and successful surgical interventions to relieve osteoarthritis pain. Control of postoperative pain is critical for patients to fully participate in the required physical therapy which is the most influential factor in effective postoperative knee rehabilitation. Currently, opiates are a mainstay for managing postoperative orthopedic surgery pain including TKA or THA pain. Recently, issues including efficacy, dependence, overdose, and death from opiates have made clinicians and researchers more critical of use of opioids for treating nonmalignant skeletal pain. In the present report, a nonopiate therapy using a monoclonal antibody raised against nerve growth factor (anti-NGF) was assessed for its ability to increase the spontaneous activity of the operated knee joint in a mouse model of orthopedic surgery pain-induced by drilling and coring the trochlear groove of the mouse femur. Horizontal activity and velocity and vertical rearing were continually assessed over a 20 hours day/night period using automated activity boxes in an effort to reduce observer bias and capture night activity when the mice are most active. At days 1 and 3, after orthopedic surgery, there was a marked reduction in spontaneous activity and vertical rearing; anti-NGF significantly attenuated this decline. The present data suggest that anti-NGF improves limb use in a rodent model of joint/orthopedic surgery and as such anti-NGF may be useful in controlling pain after orthopedic surgeries such as TKA or THA.

  17. Abnormalities in auditory efferent activities in children with selective mutism.

    PubMed

    Muchnik, Chava; Ari-Even Roth, Daphne; Hildesheimer, Minka; Arie, Miri; Bar-Haim, Yair; Henkin, Yael

    2013-01-01

    Two efferent feedback pathways to the auditory periphery may play a role in monitoring self-vocalization: the middle-ear acoustic reflex (MEAR) and the medial olivocochlear bundle (MOCB) reflex. Since most studies regarding the role of auditory efferent activity during self-vocalization were conducted in animals, human data are scarce. The working premise of the current study was that selective mutism (SM), a rare psychiatric disorder characterized by consistent failure to speak in specific social situations despite the ability to speak normally in other situations, may serve as a human model for studying the potential involvement of auditory efferent activity during self-vocalization. For this purpose, auditory efferent function was assessed in a group of 31 children with SM and compared to that of a group of 31 normally developing control children (mean age 8.9 and 8.8 years, respectively). All children exhibited normal hearing thresholds and type A tympanograms. MEAR and MOCB functions were evaluated by means of acoustic reflex thresholds and decay functions and the suppression of transient-evoked otoacoustic emissions, respectively. Auditory afferent function was tested by means of auditory brainstem responses (ABR). Results indicated a significantly higher proportion of children with abnormal MEAR and MOCB function in the SM group (58.6 and 38%, respectively) compared to controls (9.7 and 8%, respectively). The prevalence of abnormal MEAR and/or MOCB function was significantly higher in the SM group (71%) compared to controls (16%). Intact afferent function manifested in normal absolute and interpeak latencies of ABR components in all children. The finding of aberrant efferent auditory function in a large proportion of children with SM provides further support for the notion that MEAR and MOCB may play a significant role in the process of self-vocalization. © 2013 S. Karger AG, Basel.

  18. Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial. ORACLE Collaborative Group.

    PubMed

    Kenyon, S L; Taylor, D J; Tarnow-Mordi, W

    2001-03-31

    Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

  19. Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury

    PubMed Central

    Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A.; Carlton, Susan M.; Walters, Edgar T.

    2017-01-01

    Abstract A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration–approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects. PMID:28073317

  20. Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

    PubMed

    Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

    2017-03-15

    A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

  1. Functional expression of KCNQ (Kv7) channels in guinea pig bladder smooth muscle and their contribution to spontaneous activity

    PubMed Central

    Anderson, U A; Carson, C; Johnston, L; Joshi, S; Gurney, A M; McCloskey, K D

    2013-01-01

    Background and Purpose The aim of the study was to determine whether KCNQ channels are functionally expressed in bladder smooth muscle cells (SMC) and to investigate their physiological significance in bladder contractility. Experimental Approach KCNQ channels were examined at the genetic, protein, cellular and tissue level in guinea pig bladder smooth muscle using RT-PCR, immunofluorescence, patch-clamp electrophysiology, calcium imaging, detrusor strip myography, and a panel of KCNQ activators and inhibitors. Key Results KCNQ subtypes 1–5 are expressed in bladder detrusor smooth muscle. Detrusor strips typically displayed TTX-insensitive myogenic spontaneous contractions that were increased in amplitude by the KCNQ channel inhibitors XE991, linopirdine or chromanol 293B. Contractility was inhibited by the KCNQ channel activators flupirtine or meclofenamic acid (MFA). The frequency of Ca2+-oscillations in SMC contained within bladder tissue sheets was increased by XE991. Outward currents in dispersed bladder SMC, recorded under conditions where BK and KATP currents were minimal, were significantly reduced by XE991, linopirdine, or chromanol, and enhanced by flupirtine or MFA. XE991 depolarized the cell membrane and could evoke transient depolarizations in quiescent cells. Flupirtine (20 μM) hyperpolarized the cell membrane with a simultaneous cessation of any spontaneous electrical activity. Conclusions and Implications These novel findings reveal the role of KCNQ currents in the regulation of the resting membrane potential of detrusor SMC and their important physiological function in the control of spontaneous contractility in the guinea pig bladder. PMID:23586426

  2. Spontaneous and electrically modulated spatiotemporal dynamics of the neocortical slow oscillation and associated local fast activity.

    PubMed

    Greenberg, Anastasia; Dickson, Clayton T

    2013-12-01

    The neocortical slow oscillation (SO; ~1Hz) of non-REM sleep and anesthesia reflects synchronized network activity composed of alternating active and silent (ON/OFF) phases at the local network and cellular level. The SO itself shows self-organized spatiotemporal dynamics as it appears to originate at unique foci on each cycle and then propagates across the cortical surface. During sleep, this rhythm is relevant for neuroplastic processes mediating memory consolidation especially since its enhancement by slow, rhythmic electrical fields improves subsequent recall. However, the neurobiological mechanism by which spontaneous or enhanced SO activity might operate on memory traces is unknown. Here we show a series of original results, using cycle to cycle tracking across multiple neocortical sites in urethane anesthetized rats: The spontaneous spatiotemporal dynamics of the SO are complex, showing interfering propagation patterns in the anterior-to-posterior plane. These patterns compete for expression and tend to alternate following phase resets that take place during the silent OFF phase of the SO. Applying sinusoidal electrical field stimulation to the anterior pole of the cerebral cortex progressively entrained local field, gamma, and multi-unit activity at all sites, while disrupting the coordination of endogenous SO activity. Field stimulation also biased propagation in the anterior-to-posterior direction and more notably, enhanced the long-range gamma synchrony between cortical regions. These results are the first to show that changes to slow wave dynamics cause enhancements in high frequency cortico-cortical communication and provide mechanistic clues into how the SO is relevant for sleep-dependent memory consolidation. © 2013.

  3. [Forskolin inhibits spontaneous contraction of gastric antral smooth muscle in rats].

    PubMed

    Jiang, Jing-Zhi; Sun, Qian; Xu, Dong-Yuan; Zhang, Mo-Han; Piao, Li-Hua; Cai, Ying-Lan; Jin, Zheng

    2013-04-25

    The aim of the present study was to investigate the effects of cyclic adenosine monophosphate (cAMP) on rat gastric antral circular smooth muscle function. Forskolin, a direct activator of adenylyl cyclase (AC), was used to observe the influences of cAMP. Multi-channel physiological recorder was used to record spontaneous contraction activity of gastric antral circular muscle from Wistar rats. And ELISA method was used to detect the change of cAMP production in perfusate. The results showed that forskolin concentration-dependently suppressed the amplitude and frequency of the spontaneous contraction of the gastric antral muscle, and lowered the baseline of contraction movement significantly. Forskolin concentration-dependently increased the production of cAMP in the perfusate, which showed a significant negative correlation with the contraction amplitude of gastric antral ring muscle. The inhibitory effect of forskolin on spontaneous contraction activity of rat gastric antral circular muscle could be blocked by cAMP-dependent protein kinase (PKA) inhibitor H-89. These results suggest forskolin increases cAMP production and then activates PKA pathway, resulting in the inhibition of the spontaneous contraction activity of rat gastric antral circular smooth muscle.

  4. Activation of the Alternative Pathway of Complement is a Feature of Preterm Parturition but Not of Spontaneous Labor at Term

    PubMed Central

    Vaisbuch, Edi; Romero, Roberto; Erez, Offer; Mazaki-Tovi, Shali; Kusanovic, Juan Pedro; Soto, Eleazar; Dong, Zhong; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Ogge, Giovanna; Pacora, Percy; Yeo, Lami; Hassan, Sonia S.

    2012-01-01

    Problem Plasma concentrations of fragment Bb (FBb) are a marker for activation of the alternative pathway of the complement system. High concentrations of FBb in maternal blood, as early as the first trimester, are associated with subsequent spontaneous preterm delivery <34 weeks of gestation. The study aim was to determine whether spontaneous preterm labor with intact membranes (PTL), intra-amniotic infection/inflammation (IAI) or labor at term are associated with alterations in circulating maternal FBb concentrations. Method of Study This cross-sectional study included women in the following groups: 1) non-pregnant (n=40); 2) normal pregnancy (gestational age range 20-36 6/7 weeks, n=63); 2) women at term not in labor (n=70); 3) women at term in spontaneous labor (n=59); 4) patients with an episode of PTL who delivered at term (n=62); 5) PTL without IAI who delivered preterm (n=30); and 6) PTL with IAI who delivered preterm (n=67). Maternal plasma FBb concentrations were determined by ELISA. Results 1) Among patients with PTL, those who had a preterm delivery either with IAI (1.21 μg/ml, IQR 0.77-2.16) or without IAI (1.13 μg/ml, IQR 0.92-2.08;) had a higher median maternal plasma FBb concentration than those who delivered at term (0.86 μg/ml, IQR 0.64-1.57; p=0.007 and p=0.026, respectively); 2) there was no difference in the median plasma FBb concentration between patients with and without IAI who delivered preterm (p=0.9); 3) in contrast, spontaneous labor at term was not associated with a significant change in the maternal plasma FBb concentration (p=0.8); 4) maternal plasma concentration of FBb did not differ significantly between normal pregnant women and the non-pregnant controls (p=0.8) and were not correlated with advancing gestational age (r −0.28, p=0.8). Conclusions 1) Preterm parturition is associated with activation of the alternative complement pathway in maternal circulation; 2) such activation is not detectable in spontaneous labor at term

  5. Idiopathic liver function test abnormality in pregnancy is associated with assisted reproduction techniques.

    PubMed

    Kopylov, Uri; Avidan, Benjamin; Papageorgiou, Neofytos P; Katz, Lior H; Sivan, Eyal; Zimlichman, Eyal; Hussein, Haya; Maor, Yaakov

    2013-02-01

    To examine the prevalence, etiology, risk factors, and outcomes of liver abnormality in pregnancy, in a tertiary medical center, and to study the potential impact of artificial reproduction techniques (ART) on the incidence and the outcome of pregnancy-related liver abnormality. A retrospective case-control study using an electronic database and patients' files. Tertiary referral center. Women in the third trimester of pregnancy who were hospitalized for delivery. None. Development of significant elevation of alanine aminotransferase (ALT ≥ 100 IU/L). Secondary outcomes included development of maternal and fetal complications. The upper limit of normal of ALT was ≥ 1.5 times and it occurred in 440 (1.6%) pregnancies; of those, 228 (0.8%) had ALT ≥ 100 IU/L. The etiology of significant liver test abnormality was idiopathic in 47% of patients. Compared with spontaneous pregnancies (295/23,793), ART was significantly associated with liver test abnormality (145/4, 520). The presence of ALT ≥ 100 IU/L in the third trimester was associated with higher rates of cesarean sections, prematurity, low birthweight, and fetal complications. A definite etiology was not determined in about half of pregnancy-associated liver test abnormality. The ART was significantly associated with liver test elevation. Significant liver test abnormality in the third trimester may have an impact on maternal and fetal/neonatal outcomes. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  6. Does Spontaneous Favorability to Power (vs. Universalism) Values Predict Spontaneous Prejudice and Discrimination?

    PubMed

    Souchon, Nicolas; Maio, Gregory R; Hanel, Paul H P; Bardin, Brigitte

    2017-10-01

    We conducted five studies testing whether an implicit measure of favorability toward power over universalism values predicts spontaneous prejudice and discrimination. Studies 1 (N = 192) and 2 (N = 86) examined correlations between spontaneous favorability toward power (vs. universalism) values, achievement (vs. benevolence) values, and a spontaneous measure of prejudice toward ethnic minorities. Study 3 (N = 159) tested whether conditioning participants to associate power values with positive adjectives and universalism values with negative adjectives (or inversely) affects spontaneous prejudice. Study 4 (N = 95) tested whether decision bias toward female handball players could be predicted by spontaneous attitude toward power (vs. universalism) values. Study 5 (N = 123) examined correlations between spontaneous attitude toward power (vs. universalism) values, spontaneous importance toward power (vs. universalism) values, and spontaneous prejudice toward Black African people. Spontaneous positivity toward power (vs. universalism) values was associated with spontaneous negativity toward minorities and predicted gender bias in a decision task, whereas the explicit measures did not. These results indicate that the implicit assessment of evaluative responses attached to human values helps to model value-attitude-behavior relations. © 2016 The Authors. Journal of Personality Published by Wiley Periodicals, Inc.

  7. A derivative of oleamide potently inhibits the spontaneous metastasis of mouse melanoma BL6 cells.

    PubMed

    Ito, Akihiko; Morita, Nobuyoshi; Miura, Daisaku; Koma, Yu-Ichiro; Kataoka, Tatsuki R; Yamasaki, Hiroshi; Kitamura, Yukihiko; Kita, Yasuyuki; Nojima, Hiroshi

    2004-10-01

    We reported previously that the abnormally augmented expression of connexin 26 (Cx26) is responsible for the enhanced spontaneous metastasis of mouse BL6 melanoma cells, and that the exogenous expression of a dominant negative form of Cx26 inhibits the spontaneous metastasis of BL6. Here we show that daily intraperitoneal (i.p.) injections of oleamide, a sleep-inducing lipid hormone, weakly inhibited the spontaneous metastasis of BL6 cells. To obtain a more effective reagent, 19 oleamide derivatives were chemically synthesized and tested for their ability to inhibit the gap junction-mediated intercellular communications (GJIC) that are formed between HeLa cells by the ectopic expression of Cx26 or Cx43. One of these, denoted metastasis inhibitor-18 (MI-18), inhibited the GJIC formed by Cx26 as well as oleamide but unlike oleamide, which is a non-selective inhibitor of connexin, it did not inhibit the GJIC formed by Cx43. Daily i.p. injections of MI-18 potently blocked the spontaneous metastasis of BL6 cells down to 15% of that in the untreated control mice. MI-18 was safe because even after >7 weeks of daily injections, the survival rate of the mice was 93%. We propose that MI-18 may serve as a novel and clinically important prototype of a potent inhibitor of spontaneous metastasis.

  8. Arginine vasopressin antagonizes the effects of prostaglandin E2 on the spontaneous activity of warm-sensitive and temperature-insensitive neurons in the medial preoptic area in rats.

    PubMed

    Xu, Jian-Hui; Hou, Xiao-Yu; Tang, Yu; Luo, Rong; Zhang, Jie; Liu, Chang; Yang, Yong-Lu

    2018-01-01

    Arginine vasopressin (AVP) plays an important role in thermoregulation and antipyresis. We have demonstrated that AVP could change the spontaneous activity of thermosensitive and temperature insensitive neurons in the preoptic area. However, whether AVP influences the effects of prostaglandin E 2 (PGE 2 ) on the spontaneous activity of neurons in the medial preoptic area (MPO) remains unclear. Our experiment showed that PGE 2 decreased the spontaneous activity of warm-sensitive neurons, and increased that of low-slope temperature-insensitive neurons in the MPO. AVP attenuated the inhibitory effect of PGE 2 on warm-sensitive neurons, and reversed the excitatory effect of PGE 2 on low-slope temperature-insensitive neurons, demonstrating that AVP antagonized the effects of PGE 2 on the spontaneous activity of these neurons. The effect of AVP was suppressed by an AVP V 1a receptor antagonist, suggesting that V 1a receptor mediated the action of AVP. We also demonstrated that AVP attenuated the PGE 2 -induced decrease in the prepotential's rate of rise in warm-sensitive neurons and the PGE 2 -induced increase in that in low-slope temperature-insensitive neurons through the V 1a receptor. Together, these data indicated that AVP antagonized the PGE 2 -induced change in the spontaneous activity of warm-sensitive and low-slope temperature-insensitive neurons in the MPO partly by reducing the PGE 2 -induced change in the prepotential of these neurons in a V 1a receptor-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Ca currents activated by spontaneous firing and synaptic disinhibition in neurons of the cerebellar nuclei

    PubMed Central

    Zheng, Nan; Raman, Indira M.

    2009-01-01

    In neurons of the cerebellar nuclei, long-term potentiation of EPSCs is induced by high-frequency synaptic excitation by mossy fibers followed by synaptic inhibition by Purkinje cells. Induction requires activation of synaptic receptors as well as voltage-gated Ca channels. To examine how Purkinje-mediated inhibition of nuclear neurons affects Ca levels during plasticity-inducing stimuli, we have combined electrophysiology, Ca imaging, and pharmacology of cerebellar nuclear neurons in mouse cerebellar slices. We find that spontaneous firing generates tonic Ca signals in both somata and dendrites, which drop during 500-ms, 100-Hz trains of Purkinje IPSPs or hyperpolarizing steps. Although the presence of low-voltage-activated (T-type) Ca channels in nuclear neurons has fostered the inference that disinhibition activates these channels, synaptic inhibition with a physiological ECl (−75 mV) fails to hyperpolarize neurons sufficiently for T-type channels to recover substantially. Consequently, after IPSPs, Ca signals return to baseline, although firing is accelerated by ∼20 Hz for ∼300 ms. Only after hyperpolarizations beyond ECl does Ca rise gradually beyond baseline, as firing further exceeds spontaneous rates. Cd2+ (100 μM), which nearly eliminates L-type, N-type, P/Q-type, and R-type Ca currents while sparing about half the T-type current, prevents Ca changes during and after hyperpolarizations to ECl. Thus, high-frequency IPSPs in cerebellar nuclear neurons evoke little post-inhibitory current through T-type channels. Instead, inhibition regulates Ca levels simply by preventing action potentials, which usually permit Ca influx through high-voltage-activated channels. The decreases and restoration of Ca levels associated with Purkinje-mediated inhibition are likely to contribute to synaptic plasticity. PMID:19657035

  10. [The diversity analysis of spontaneous cerebrospinal fluid otorrhea between young children and adults].

    PubMed

    Liu, J; Mei, L Y; He, C F; Feng, Y

    2016-11-01

    Objective: To assess the diversity of spontaneous cerebrospinal fluid(CSF)otorrhear in clinical manifestation,CT,leakage sites and surgical operation between young children and adults. Method: We conducted a retrospective study of 6 consecutive patients who were all underwent the surgery through the transmastoid approach,including 4 adults patients and 2 children.In the 4 adults patients,two patients' bony defects lay on the tegmen mastoideum,one lay on the tegmen tympani,and another one lay on the sinus meningioma angle.None of the 4 adults patients had abnormal inner ear structures.Materials used in repair included free muscle graft,temporalis fascia,and fibrin glue of the 4 adults patients.The 2 children patients were diagnosed with congenital abnormalities of the lateral inner ear,who had bony defects of the foot plate or fenestra vestibule.Materials used in repair included free muscle graft,temporalis fascia,and musclein sequence. Result: No CSF leaks recurred after the operation except one adults patient,who's left ear recurred two times and experienced three operations. Conclusion: The clinical manifestations of spontaneous CSF otorrhea between young children and adults are different,the HRCT scan on temporal bone before the operation is very important.Especially foradults patients,making sure of theleakagesites and numbers isvaluable and significance for thesurgical procedure selection.. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

  11. Liver transplantation nearly normalizes brain spontaneous activity and cognitive function at 1 month: a resting-state functional MRI study.

    PubMed

    Cheng, Yue; Huang, Lixiang; Zhang, Xiaodong; Zhong, Jianhui; Ji, Qian; Xie, Shuangshuang; Chen, Lihua; Zuo, Panli; Zhang, Long Jiang; Shen, Wen

    2015-08-01

    To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

  12. Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

    PubMed Central

    Olivier, Alicia K.; Yi, Yaling; Sun, Xingshen; Sui, Hongshu; Liang, Bo; Hu, Shanming; Xie, Weiliang; Fisher, John T.; Keiser, Nicholas W.; Lei, Diana; Zhou, Weihong; Yan, Ziying; Li, Guiying; Evans, Turan I.A.; Meyerholz, David K.; Wang, Kai; Stewart, Zoe A.; Norris, Andrew W.; Engelhardt, John F.

    2012-01-01

    Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. PMID:22996690

  13. Spontaneous membrane formation and self-encapsulation of active rods in an inhomogeneous motility field

    NASA Astrophysics Data System (ADS)

    Grauer, Jens; Löwen, Hartmut; Janssen, Liesbeth M. C.

    2018-02-01

    We study the collective dynamics of self-propelled rods in an inhomogeneous motility field. At the interface between two regions of constant but different motility, a smectic rod layer is spontaneously created through aligning interactions between the active rods, reminiscent of an artificial, semipermeable membrane. This "active membrane" engulfes rods which are locally trapped in low-motility regions and thereby further enhances the trapping efficiency by self-organization, an effect which we call "self-encapsulation." Our results are gained by computer simulations of self-propelled rod models confined on a two-dimensional planar or spherical surface with a stepwise constant motility field, but the phenomenon should be observable in any geometry with sufficiently large spatial inhomogeneity. We also discuss possibilities to verify our predictions of active-membrane formation in experiments of self-propelled colloidal rods and vibrated granular matter.

  14. Nonsurgical correction of congenital ear abnormalities in the newborn: Case series.

    PubMed

    Smith, Wg; Toye, Jw; Reid, A; Smith, Rw

    2005-07-01

    To determine whether a simple, nonsurgical treatment for congenital ear abnormalities (lop-ear, Stahl's ear, protruding ear, cryptotia) improved the appearance of ear abnormalities in newborns at six weeks of age. This is a descriptive case series. All newborns with identified abnormalities were referred by their family physician to one paediatrician (WGS) in a small level 2 perinatal centre. The ears were waxed and taped in a standard manner within 10 days of birth. Pictures were taken before taping and at the end of taping (one month). All patients and pictures were assessed by one plastic surgeon (JWT) at six weeks of age and scored using a standard scoring system. A telephone survey of the nontreatment group was conducted. The total number of ears assessed was 90. Of this total, 69 ears were taped and fully evaluated in the study (77%). The refusal rate was 23%. In the treatment group, 59% had lop-ear, 19% had Stahl's ear, 17% had protruding ear and 3% had cryptotia. Overall correction (excellent/improved) for the treatment group was 90% (100% for lop-ear, 100% for Stahl's ear, 67% for protruding ear and 0% for cryptotia). In the nontreatment (refusal) group, 67% of the ears failed to correct spontaneously. No complications were recognized by the authors or parents by six weeks. The percentage of newborns in one year in the perinatal centre with recognized ear abnormalities was 6% (90 of 1600). A simple, nonsurgical treatment in a Caucasian population appeared to be very effective in correcting congenital ear abnormalities with no complications and high patient/parent satisfaction.

  15. [INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

    PubMed

    Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

    2016-03-30

    Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

  16. Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models.

    PubMed

    Yokoi, Fumiaki; Dang, Mai T; Zhou, Tong; Li, Yuqing

    2012-02-15

    DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ε-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ε-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ε-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ε-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients.

  17. Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice.

    PubMed

    Wang, Xiaoli; Chen, Xiaojiao; Feng, Xuejiao; Chang, Fei; Chen, Minjian; Xia, Yankai; Chen, Ling

    2015-12-15

    Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose-dependently fetal death during GD12.5-16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo-conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS-exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis.

  18. Triclosan causes spontaneous abortion accompanied by decline of estrogen sulfotransferase activity in humans and mice

    PubMed Central

    Wang, Xiaoli; Chen, Xiaojiao; Feng, Xuejiao; Chang, Fei; Chen, Minjian; Xia, Yankai; Chen, Ling

    2015-01-01

    Triclosan (TCS), an antibacterial agent, is identified in serum and urine of humans. Here, we show that the level of urinary TCS in 28.3% patients who had spontaneous abortion in mid-gestation were increased by 11.3-fold (high-TCS) compared with normal pregnancies. Oral administration of TCS (10 mg/kg/day) in mice (TCS mice) caused an equivalent urinary TCS level as those in the high-TCS abortion patients. The TCS-exposure from gestation day (GD) 5.5 caused dose-dependently fetal death during GD12.5–16.5 with decline of live fetal weight. GD15.5 TCS mice appeared placental thrombus and tissue necrosis with enhancement of platelet aggregation. The levels of placenta and plasma estrogen sulfotransferase (EST) mRNA and protein in TCS mice or high-TCS abortion patients were not altered, but their EST activities were significantly reduced compared to controls. Although the levels of serum estrogen (E2) in TCS mice and high-TCS abortion patients had no difference from controls, their ratio of sulfo-conjugated E2 and unconjugated E2 was reduced. The estrogen receptor antagonist ICI-182,780 prevented the enhanced platelet aggregation and placental thrombosis and attenuated the fetal death in TCS mice. The findings indicate that TCS-exposure might cause spontaneous abortion probably through inhibition of EST activity to produce placental thrombosis. PMID:26666354

  19. Characterizing the complexity of spontaneous motor unit patterns of amyotrophic lateral sclerosis using approximate entropy

    NASA Astrophysics Data System (ADS)

    Zhou, Ping; Barkhaus, Paul E.; Zhang, Xu; Zev Rymer, William

    2011-10-01

    This paper presents a novel application of the approximate entropy (ApEn) measurement for characterizing spontaneous motor unit activity of amyotrophic lateral sclerosis (ALS) patients. High-density surface electromyography (EMG) was used to record spontaneous motor unit activity bilaterally from the thenar muscles of nine ALS subjects. Three distinct patterns of spontaneous motor unit activity (sporadic spikes, tonic spikes and high-frequency repetitive spikes) were observed. For each pattern, complexity was characterized by calculating the ApEn values of the representative signal segments. A sliding window over each segment was also introduced to quantify the dynamic changes in complexity for the different spontaneous motor unit patterns. We found that the ApEn values for the sporadic spikes were the highest, while those of the high-frequency repetitive spikes were the lowest. There is a significant difference in mean ApEn values between two arbitrary groups of the three spontaneous motor unit patterns (P < 0.001). The dynamic ApEn curve from the sliding window analysis is capable of tracking variations in EMG activity, thus providing a vivid, distinctive description for different patterns of spontaneous motor unit action potentials in terms of their complexity. These findings expand the existing knowledge of spontaneous motor unit activity in ALS beyond what was previously obtained using conventional linear methods such as firing rate or inter-spike interval statistics.

  20. Spontaneous food allergy in Was-/- mice occurs independent of FcεRI-mediated mast cell activation.

    PubMed

    Lexmond, W S; Goettel, J A; Sallis, B F; McCann, K; Rings, E H H M; Jensen-Jarolim, E; Nurko, S; Snapper, S B; Fiebiger, E

    2017-12-01

    Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was -/- mice recapitulates the pathology of a conventional disease model and/or human food allergy. Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was -/- mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was -/- Fcer1a -/- mice. Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was -/- model. Oral administration of ovalbumin (OVA) in Was -/- mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was -/- mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was -/- mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils. Was -/- mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  1. Linked functional network abnormalities during intrinsic and extrinsic activity in schizophrenia as revealed by a data-fusion approach.

    PubMed

    Hashimoto, Ryu-Ichiro; Itahashi, Takashi; Okada, Rieko; Hasegawa, Sayaka; Tani, Masayuki; Kato, Nobumasa; Mimura, Masaru

    2018-01-01

    Abnormalities in functional brain networks in schizophrenia have been studied by examining intrinsic and extrinsic brain activity under various experimental paradigms. However, the identified patterns of abnormal functional connectivity (FC) vary depending on the adopted paradigms. Thus, it is unclear whether and how these patterns are inter-related. In order to assess relationships between abnormal patterns of FC during intrinsic activity and those during extrinsic activity, we adopted a data-fusion approach and applied partial least square (PLS) analyses to FC datasets from 25 patients with chronic schizophrenia and 25 age- and sex-matched normal controls. For the input to the PLS analyses, we generated a pair of FC maps during the resting state (REST) and the auditory deviance response (ADR) from each participant using the common seed region in the left middle temporal gyrus, which is a focus of activity associated with auditory verbal hallucinations (AVHs). PLS correlation (PLS-C) analysis revealed that patients with schizophrenia have significantly lower loadings of a component containing positive FCs in default-mode network regions during REST and a component containing positive FCs in the auditory and attention-related networks during ADR. Specifically, loadings of the REST component were significantly correlated with the severities of positive symptoms and AVH in patients with schizophrenia. The co-occurrence of such altered FC patterns during REST and ADR was replicated using PLS regression, wherein FC patterns during REST are modeled to predict patterns during ADR. These findings provide an integrative understanding of altered FCs during intrinsic and extrinsic activity underlying core schizophrenia symptoms.

  2. A New Mouse Model That Spontaneously Develops Chronic Liver Inflammation and Fibrosis

    PubMed Central

    Fransén-Pettersson, Nina; Duarte, Nadia; Nilsson, Julia; Lundholm, Marie; Mayans, Sofia; Larefalk, Åsa; Hannibal, Tine D.; Hansen, Lisbeth; Schmidt-Christensen, Anja; Ivars, Fredrik; Cardell, Susanna; Palmqvist, Richard; Rozell, Björn

    2016-01-01

    Here we characterize a new animal model that spontaneously develops chronic inflammation and fibrosis in multiple organs, the non-obese diabetic inflammation and fibrosis (N-IF) mouse. In the liver, the N-IF mouse displays inflammation and fibrosis particularly evident around portal tracts and central veins and accompanied with evidence of abnormal intrahepatic bile ducts. The extensive cellular infiltration consists mainly of macrophages, granulocytes, particularly eosinophils, and mast cells. This inflammatory syndrome is mediated by a transgenic population of natural killer T cells (NKT) induced in an immunodeficient NOD genetic background. The disease is transferrable to immunodeficient recipients, while polyclonal T cells from unaffected syngeneic donors can inhibit the disease phenotype. Because of the fibrotic component, early on-set, spontaneous nature and reproducibility, this novel mouse model provides a unique tool to gain further insight into the underlying mechanisms mediating transformation of chronic inflammation into fibrosis and to evaluate intervention protocols for treating conditions of fibrotic disorders. PMID:27441847

  3. Spontaneous distal rupture of the plantar fascia.

    PubMed

    Gitto, Salvatore; Draghi, Ferdinando

    2018-07-01

    Spontaneous ruptures of the plantar fascia are uncommon injuries. They typically occur at its calcaneal insertion and usually represent a complication of plantar fasciitis and local treatment with steroid injections. In contrast, distal ruptures commonly result from traumatic injuries. We describe the case of a spontaneous distal rupture of the plantar fascia in a 48-year-old woman with a low level of physical activity and no history of direct injury to the foot, plantar fasciitis, or steroid injections. © 2017 Wiley Periodicals, Inc.

  4. The role of abnormal fetal heart rate in scheduling chorionic villus sampling.

    PubMed

    Yagel, S; Anteby, E; Ron, M; Hochner-Celnikier, D; Achiron, R

    1992-09-01

    To assess the value of fetal heart rate (FHR) measurements in predicting spontaneous fetal loss in pregnancies scheduled for chorionic villus sampling (CVS). A prospective descriptive study. Two hospital departments of obstetrics and gynaecology in Israel. 114 women between 9 and 11 weeks gestation scheduled for chorionic villus sampling (CVS). Fetal heart rate was measured by transvaginal Doppler ultrasound and compared with a monogram established from 75 fetuses. Whenever a normal FHR was recorded, CVS was performed immediately. 106 women had a normal FHR and underwent CVS; two of these pregnancies ended in miscarriage. In five pregnancies no fetal heart beats could be identified and fetal death was diagnosed. In three pregnancies an abnormal FHR was recorded and CVS was postponed; all three pregnancies ended in miscarriage within 2 weeks. Determination of FHR correlated with crown-rump length could be useful in predicting spontaneous miscarriage before performing any invasive procedure late in the first trimester.

  5. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    PubMed

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  6. Hox-C9 activates the intrinsic pathway of apoptosis and is associated with spontaneous regression in neuroblastoma.

    PubMed

    Kocak, H; Ackermann, S; Hero, B; Kahlert, Y; Oberthuer, A; Juraeva, D; Roels, F; Theissen, J; Westermann, F; Deubzer, H; Ehemann, V; Brors, B; Odenthal, M; Berthold, F; Fischer, M

    2013-04-11

    Neuroblastoma is an embryonal malignancy of the sympathetic nervous system. Spontaneous regression and differentiation of neuroblastoma is observed in a subset of patients, and has been suggested to represent delayed activation of physiologic molecular programs of fetal neuroblasts. Homeobox genes constitute an important family of transcription factors, which play a fundamental role in morphogenesis and cell differentiation during embryogenesis. In this study, we demonstrate that expression of the majority of the human HOX class I homeobox genes is significantly associated with clinical covariates in neuroblastoma using microarray expression data of 649 primary tumors. Moreover, a HOX gene expression-based classifier predicted neuroblastoma patient outcome independently of age, stage and MYCN amplification status. Among all HOX genes, HOXC9 expression was most prominently associated with favorable prognostic markers. Most notably, elevated HOXC9 expression was significantly associated with spontaneous regression in infant neuroblastoma. Re-expression of HOXC9 in three neuroblastoma cell lines led to a significant reduction in cell viability, and abrogated tumor growth almost completely in neuroblastoma xenografts. Neuroblastoma growth arrest was related to the induction of programmed cell death, as indicated by an increase in the sub-G1 fraction and translocation of phosphatidylserine to the outer membrane. Programmed cell death was associated with the release of cytochrome c from the mitochondria into the cytosol and activation of the intrinsic cascade of caspases, indicating that HOXC9 re-expression triggers the intrinsic apoptotic pathway. Collectively, our results show a strong prognostic impact of HOX gene expression in neuroblastoma, and may point towards a role of Hox-C9 in neuroblastoma spontaneous regression.

  7. Abnormal brain activation in excoriation (skin-picking) disorder: evidence from an executive planning fMRI study

    PubMed Central

    Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R.; Grant, Jon E.

    2016-01-01

    Background Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims To probe the function of fronto-striatal circuitry in SPD. Method Eighteen participants with SPD and 15 matched healthy controls undertook an executive planning task (Tower of London) during functional magnetic resonance imaging (fMRI). Activation during planning was compared between groups using region of interest and whole-brain permutation cluster approaches. Results The SPD group exhibited significant functional underactivation in a cluster encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. Conclusions Abnormalities of neural regions involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive–compulsive spectrum disorders. PMID:26159604

  8. Spontaneous Generation of Chirality in Simple Diaryl Ethers.

    PubMed

    Lennartson, Anders; Hedström, Anna; Håkansson, Mikael

    2015-07-01

    We studied the spontaneous formation of chiral crystals of four diaryl ethers, 3-phenoxybenzaldehyde, 1; 1,3-dimethyl-2-phenoxybenzene, 2; di(4-aminophenyl) ether, 3; and di(p-tolyl) ether, 4. Compounds 1, 3, and 4 form conformationally chiral molecules in the solid state, while the chirality of 2 arises from the formation of supramolecular helices. Compound 1 is a liquid at ambient temperature, but 2-4 are crystalline, and solid-state CD-spectroscopy showed that they could be obtained as optically active bulk samples. It should be noted that the optical activity arise upon crystallization, and no optically active precursors were used. Indeed, even commercial samples of 3 and 4 were found to be optically active, giving evidence for the ease at which total spontaneous resolution may occur in certain systems. © 2015 Wiley Periodicals, Inc.

  9. Certain aspects of normal and abnormal motility of sphincter of Oddi.

    PubMed

    Coelho, J C; Moody, F G

    1987-01-01

    Applications of electromyographic and endoscopic manometric techniques in experimental and clinical studies have enhanced our knowledge of the normal physiology and motility disturbances of the sphincter of Oddi. The sphincter of Oddi has an active role in coordinating the time and rate of secretion of biliopancreatic juice into the duodenum. In the opossum, the sphincter of Oddi exhibits spontaneous contractions that migrate distally along the sphincter and expels its contents into the duodenum. Although the motor activity of the sphincter of Oddi is independent from that of the duodenum, there is a correlation between the frequency of bursts of spike potentials in the sphincter of Oddi and the migrating motor complex phases in the duodenum. Abnormal motility of the sphincter of Oddi has been reported during endoscopic manometric evaluation of patients with choledocholithiasis and sphincter of Oddi dyskinesia. Patients with common bile duct stones have an increase in the frequency of retrograde propagation of phasic waves. Elevation of basal pressure as well as an increase in the frequency and amplitude of sphincter of Oddi phasic waves and the common bile duct-duodenum gradient pressure may occur in patients with sphincter of Oddi dyskinesia. Endoscopic manometric studies of the sphincter of Oddi may become an important method to diagnose sphincter of Oddi dyskinesia.

  10. Cortical Alpha Activity in Schizoaffective Patients

    PubMed Central

    Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L.; Majidi, Hamid

    2017-01-01

    Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT) receptor function in schizoaffective disorder (SA), a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA. Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders–Fourth Edition (DSM–IV) criteria for SA, and in 39 healthy controls. Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025]. Conclusion: A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations. PMID:28496495

  11. Cortical Alpha Activity in Schizoaffective Patients.

    PubMed

    Moeini, Mahdi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Zarafshan, Hadi; Fazio, Rachel L; Majidi, Hamid

    2017-01-01

    Objective: Electrophysiological studies have identified abnormal oscillatory activities in the cerebral cortex in schizophrenia and mood disorders. Biological and pathophysiological evidence suggests specific deficits in serotonin (5-HT) receptor function in schizoaffective disorder (SA), a clinical syndrome with characteristics of both schizophrenia and bipolar disorder. This study investigated alpha oscillations in patients with SA. Method: Electroencephalography was used to measure ongoing and evoked alpha oscillations in 38 adults meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for SA, and in 39 healthy controls. Results: Spontaneous alpha power of the participants with SA was significantly lower than that of healthy participants [F (1, 75) = 8.81, P < 0.01]. Evoked alpha activity was also decreased in SA compared to controls [F (1, 75) = 5.67, P = 0.025]. Conclusion : A strong reduction of alpha power in the posterior regions may reflect abnormality in the thalamocortical circuits. It is shown that hypoxia and reduced cerebral blood flow is associated with reduced alpha activity among different regions of the brain. Therefore, it can be concluded that greatly decreased alpha activity, particularly in centro-parietal and occipital regions, is related to SA symptoms such as hallucinations.

  12. Familial skewed X inactivation: a molecular trait associated with high spontaneous-abortion rate maps to Xq28.

    PubMed Central

    Pegoraro, E; Whitaker, J; Mowery-Rushton, P; Surti, U; Lanasa, M; Hoffman, E P

    1997-01-01

    We report a family ascertained for molecular diagnosis of muscular dystrophy in a young girl, in which preferential activation (> or = 95% of cells) of the paternal X chromosome was seen in both the proband and her mother. To determine the molecular basis for skewed X inactivation, we studied X-inactivation patterns in peripheral blood and/or oral mucosal cells from 50 members of this family and from a cohort of normal females. We found excellent concordance between X-inactivation patterns in blood and oral mucosal cell nuclei in all females. Of the 50 female pedigree members studied, 16 showed preferential use (> or = 95% cells) of the paternal X chromosome; none of 62 randomly selected females showed similarly skewed X inactivation was maternally inherited in this family. A linkage study using the molecular trait of skewed X inactivation as the scored phenotype localized this trait to Xq28 (DXS1108; maximum LOD score [Zmax] = 4.34, recombination fraction [theta] = 0). Both genotyping of additional markers and FISH of a YAC probe in Xq28 showed a deletion spanning from intron 22 of the factor VIII gene to DXS115-3. This deletion completely cosegregated with the trait (Zmax = 6.92, theta = 0). Comparison of clinical findings between affected and unaffected females in the 50-member pedigree showed a statistically significant increase in spontaneous-abortion rate in the females carrying the trait (P < .02). To our knowledge, this is the first gene-mapping study of abnormalities of X-inactivation patterns and is the first association of a specific locus for recurrent spontaneous abortion in a cytogenetically normal family. The involvement of this locus in cell lethality, cell-growth disadvantage, developmental abnormalities, or the X-inactivation process is discussed. Images Figure 4 Figure 7 PMID:9245997

  13. Structural abnormalities and altered regional brain activity in multiple sclerosis with simple spinal cord involvement.

    PubMed

    Yin, Ping; Liu, Yi; Xiong, Hua; Han, Yongliang; Sah, Shambhu Kumar; Zeng, Chun; Wang, Jingjie; Li, Yongmei

    2018-02-01

    To assess the changes of the structural and functional abnormalities in multiple sclerosis with simple spinal cord involvement (MS-SSCI) by using resting-state functional MRI (RS-fMRI), voxel based morphology (VBM) and diffusion tensor tractography. The amplitude of low-frequency fluctuation (ALFF) of 22 patients with MS-SSCI and 22 healthy controls (HCs) matched for age, gender and education were compared by using RS-fMRI. We also compared the volume, fractional anisotropy (FA) and apparent diffusion coefficient of the brain regions in baseline brain activity by using VBM and diffusion tensor imaging. The relationships between the expanded disability states scale (EDSS) scores, changed parameters of structure and function were further explored. (1) Compared with HCs, the ALFF of the bilateral hippocampus and right middle temporal gyrus in MS-SSCI decreased significantly. However, patients exhibited increased ALFF in the left middle frontal gyrus, left posterior cingulate gyrus and right middle occipital gyrus ( two-sample t-test, after AlphaSim correction, p < 0.01, voxel size > 40). The volume of right middle frontal gyrus reduced significantly (p < 0.01). The FA and ADC of right hippocampus, the FA of left hippocampus and right middle temporal gyrus were significantly different. (2) A significant correlation between EDSS scores and ALFF was noted only in the left posterior cingulate gyrus. Our results detected structural and functional abnormalities in MS-SSCI and functional parameters were associated with clinical abnormalities. Multimodal imaging plays an important role in detecting structural and functional abnormalities in MS-SSCI. Advances in knowledge: This is the first time to apply RS-fMRI, VBM and diffusion tensor tractography to study the structural and functional abnormalities in MS-SSCI, and to explore its correlation with EDSS score.

  14. Identification of age-dependent motor and neuropsychological behavioural abnormalities in a mouse model of Mucopolysaccharidosis Type II

    PubMed Central

    Gleitz, Hélène F. E.; O’Leary, Claire; Holley, Rebecca J.

    2017-01-01

    Severe mucopolysaccharidosis type II (MPS II) is a progressive lysosomal storage disease caused by mutations in the IDS gene, leading to a deficiency in the iduronate-2-sulfatase enzyme that is involved in heparan sulphate and dermatan sulphate catabolism. In constitutive form, MPS II is a multi-system disease characterised by progressive neurocognitive decline, severe skeletal abnormalities and hepatosplenomegaly. Although enzyme replacement therapy has been approved for treatment of peripheral organs, no therapy effectively treats the cognitive symptoms of the disease and novel therapies are in development to remediate this. Therapeutic efficacy and subsequent validation can be assessed using a variety of outcome measures that are translatable to clinical practice, such as behavioural measures. We sought to consolidate current knowledge of the cognitive, skeletal and motor abnormalities present in the MPS II mouse model by performing time course behavioural examinations of working memory, anxiety, activity levels, sociability and coordination and balance, up to 8 months of age. Cognitive decline associated with alterations in spatial working memory is detectable at 8 months of age in MPS II mice using spontaneous alternation, together with an altered response to novel environments and anxiolytic behaviour in the open-field. Coordination and balance on the accelerating rotarod were also significantly worse at 8 months, and may be associated with skeletal changes seen in MPS II mice. We demonstrate that the progressive nature of MPS II disease is also seen in the mouse model, and that cognitive and motor differences are detectable at 8 months of age using spontaneous alternation, the accelerating rotarod and the open-field tests. This study establishes neurological, motor and skeletal measures for use in pre-clinical studies to develop therapeutic approaches in MPS II. PMID:28207863

  15. A spontaneous change in the oxidation states of Pd/WO3 toward an active phase during catalytic cycles of CO oxidation

    NASA Astrophysics Data System (ADS)

    Jeon, Byungwook; Kim, Ansoon; Lee, Young-Ahn; Seo, Hyungtak; Kim, Yu Kwon

    2017-11-01

    CO oxidation over Pd/WO3 films prepared on a glass substrate has been examined at the substrate temperature of 150 - 250 °C and pressures less than 1 Torr with a stoichiometric mixture of CO and O2. Under the given reaction condition, the chemical states of the Pd/WO3 film gradually change into the most catalytically active form with the highest saturation reaction rate regardless of the initial oxidation states. The measured CO oxidation rate over the Pd/WO3 is strongly dependent on the chemical states of Pd and W. Either metallic Pd or fully oxidized PdO phase is not as catalytically active as the active form with mixed metallic Pd and thin PdO layers supported on WO3 with partially reduced W5+ state which is spontaneously obtained during the catalytic reaction cycles. Our results indicate that the facile oxygen transfer between Pd and WO3 layers not only facilitate the spontaneous changes into the active form, but also act as a promotional role in CO oxidation over the Pd layer.

  16. Spontaneous physical activity protects against fat mass gain

    PubMed Central

    Teske, Jennifer A.; Billington, Charles J.; Kuskowski, Michael A.; Kotz, Catherine M.

    2011-01-01

    It is unclear whether elevated spontaneous physical activity (SPA, very low-intensity physical activity) positively influences body composition long-term. Objective We determined whether SPA and caloric intake were differentially related to the growth curve trajectories of body weight, FM and FFM between obesity resistant and Sprague-Dawley rats at specific age intervals. Design and Subjects Body composition, SPA and caloric intake were measured in selectively-bred obesity resistant and out-bred Sprague-Dawley rats from 1-18 mo. Data from development throughout maturation were analyzed by longitudinal growth curve modeling to determine the rate and acceleration of body weight, fat mass (FM) and fat-free mass (FFM) gain. Results Obesity resistant rats had a lower rate of FM gain overall, a lower acceleration in body weight early in life, significantly greater SPA and lower cumulative caloric intake. Greater SPA in obesity resistant rats was significantly associated with a lower rate of FM gain overall and lower acceleration in body weight early in life. Obesity resistant rats lost less FFM compared to Sprague-Dawley rats despite that obesity resistant rats had a lower acceleration in FFM gain early in life. Obesity resistant rats gained less FM and more FFM per gram body weight and were less energy efficient than Sprague-Dawley rats. Caloric intake was significantly and positively related to body weight, FM and FFM gain in both groups. Circadian patterns of caloric intake were group and age-dependent. Our data demonstrate that elevated and sustained SPA during development and over the lifespan are related to the reduced the rate of FM gain and may preserve FFM. Conclusion These data support the idea that SPA level is a reproducible marker that reliably predicts propensity for obesity in rats, and that elevated levels of SPA maintained during the lifespan promote a lean phenotype. PMID:21610695

  17. Right ventricular outflow tract high-density endocardial unipolar voltage mapping in patients with Brugada syndrome: evidence for electroanatomical abnormalities.

    PubMed

    Letsas, Konstantinos P; Efremidis, Michael; Vlachos, Konstantinos; Georgopoulos, Stamatis; Karamichalakis, Nikolaos; Asvestas, Dimitrios; Valkanas, Kosmas; Korantzopoulos, Panagiotis; Liu, Tong; Sideris, Antonios

    2017-05-02

    Epicardial structural abnormalities at the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Electroanatomical endocardial unipolar voltage mapping is an emerging tool that accurately identifies epicardial abnormalities in different clinical settings. This study investigated whether endocardial unipolar voltage mapping of the RVOT detects electroanatomical abnormalities in patients with BrS. Ten asymptomatic patients (8 males, 34.5 ± 11.2 years) with spontaneous type 1 ECG pattern of BrS and negative late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-c-MRI) underwent high-density endocardial electroanatomical mapping (>800 points). Using a cut-off of 1 mV and 4 mV for normal bipolar and unipolar voltage, respectively, derived from 20 control patients without structural heart disease established by LGE-c-MRI, the extend of low-voltage areas within the RVOT was estimated using a specific calculation software. The mean RVOT area presenting low-voltage bipolar signals in BrS patients was 3.4 ± 1.7 cm2 (range 1.5-7 cm2). A significantly greater area of abnormal unipolar signals was identified (12.6 ± 4.6 cm2 [range 7-22 cm2], P: 0.001). Both bipolar and unipolar electroanatomical abnormalities were mainly located at the free wall of the RVOT. The mean RVOT activation time was significantly prolonged in BrS patients compared to control population (86.4 ± 16.5 vs. 63.4 ± 9.7 ms, P < 0.001). Isochronal mapping demonstrated lines of conduction slowing within the RVOT in 8/10 BrS patients. Wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities are identified at the RVOT of BrS patients. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  18. Hexamethonium attenuates sympathetic activity and blood pressure in spontaneously hypertensive rats.

    PubMed

    Li, Peng; Gong, Jue-Xiao; Sun, Wei; Zhou, Bin; Kong, Xiang-Qing

    2015-11-01

    Sympathetic activity is enhanced in heart failure and hypertensive rats. The aims of the current study were: i) To investigate the association between renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) in response to intravenous injection of the ganglionic blocker hexamethonium; and ii) to determine whether normal Wistar rats and spontaneously hypertensive rats (SHRs) differ in their response to hexamethonium. RSNA and MAP were recorded in anaesthetized rats. Intravenous injection of four doses of hexamethonium significantly reduced the RSNA, MAP and heart rate (HR) in the Wistar rats and SHRs. There were no significant differences in the RSNA, MAP or HR between Wistar rats and SHRs at the two lowest doses of hexamethonium. However, the two highest doses of hexamethonium resulted in a greater reduction in the RSNA and MAP in SHRs compared with Wistar rats. There was a significant positive correlation between the alterations in RSNA and MAP in response to the intravenous injection of hexamethonium in the Wistar rats and SHRs. There were no significant differences in the timing of the maximal effects on RSNA, MAP or HR or in recovery following hexamethonium treatment. These results suggest that there is an association between the RSNA and MAP response to intravenous injection of hexamethonium and that the alterations in MAP in response to hexamethonium may be used to evaluate basal sympathetic nerve activity.

  19. Hemostatic abnormalities in Noonan syndrome.

    PubMed

    Artoni, Andrea; Selicorni, Angelo; Passamonti, Serena M; Lecchi, Anna; Bucciarelli, Paolo; Cerutti, Marta; Cianci, Paola; Gianniello, Francesca; Martinelli, Ida

    2014-05-01

    A bleeding diathesis is a common feature of Noonan syndrome, and various coagulation abnormalities have been reported. Platelet function has never been carefully investigated. The degree of bleeding diathesis in a cohort of patients with Noonan syndrome was evaluated by a validated bleeding score and investigated with coagulation and platelet function tests. If ratios of prothrombin time and/or activated partial thromboplastin time were prolonged, the activity of clotting factors was measured. Individuals with no history of bleeding formed the control group. The study population included 39 patients and 28 controls. Bleeding score was ≥2 (ie, suggestive of a moderate bleeding diathesis) in 15 patients (38.5%) and ≥4 (ie, suggestive of a severe bleeding diathesis) in 7 (17.9%). Abnormal coagulation and/or platelet function tests were found in 14 patients with bleeding score ≥2 (93.3%) but also in 21 (87.5%) of those with bleeding score <2. The prothrombin time and activated partial thromboplastin time were prolonged in 18 patients (46%) and partial deficiency of factor VII, alone or in combination with the deficiency of other vitamin K-dependent factors, was the most frequent coagulation abnormality. Moreover, platelet aggregation and secretion were reduced in 29 of 35 patients (82.9%, P < .01 for all aggregating agents). Nearly 40% of patients with the Noonan syndrome had a bleeding diathesis and >90% of them had platelet function and/or coagulation abnormalities. Results of these tests should be taken into account in the management of bleeding or invasive procedures in these patients. Copyright © 2014 by the American Academy of Pediatrics.

  20. Abnormal nuclear envelopes in the striatum and motor deficits in DYT11 myoclonus-dystonia mouse models

    PubMed Central

    Yokoi, Fumiaki; Dang, Mai T.; Zhou, Tong; Li, Yuqing

    2012-01-01

    DYT11 myoclonus-dystonia (M-D) is a movement disorder characterized by myoclonic jerks with dystonic symptoms and caused by mutations in paternally expressed SGCE, which codes for ɛ-sarcoglycan. Paternally inherited Sgce heterozygous knock-out (KO) mice exhibit motor deficits and spontaneous myoclonus. Abnormal nuclear envelopes have been reported in cellular and mouse models of early-onset DYT1 generalized torsion dystonia; however, the relationship between the abnormal nuclear envelopes and motor symptoms are not clear. Furthermore, it is not known whether abnormal nuclear envelope exists in non-DYT1 dystonia. In the present study, abnormal nuclear envelopes in the striatal medium spiny neurons (MSNs) were found in Sgce KO mice. To analyze whether the loss of ɛ-sarcoglycan in the striatum alone causes abnormal nuclear envelopes, motor deficits or myoclonus, we produced paternally inherited striatum-specific Sgce conditional KO (Sgce sKO) mice and analyzed their phenotypes. Sgce sKO mice exhibited motor deficits in both beam-walking and accelerated rotarod tests, while they did not exhibit abnormal nuclear envelopes, alteration in locomotion, or myoclonus. The results suggest that the loss of ɛ-sarcoglycan in the striatum contributes to motor deficits, while it alone does not produce abnormal nuclear envelopes or myoclonus. Development of therapies targeting the striatum to compensate for the loss of ɛ-sarcoglycan function may rescue the motor deficits in DYT11 M-D patients. PMID:22080833

  1. UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures

    PubMed Central

    Liu, Yidan; Zhang, Bin; Meng, Xiaoyu; Korn, Matthew J.; Parent, Jack M.; Lu, Lin-Yu; Yu, Xiaochun

    2017-01-01

    ABSTRACT The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Loss of UHRF1 abolishes 5mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but its biologic function is not clear. Here, we have generated Uhrf2 knockout mice and characterized the role of UHRF2 in vivo. Uhrf2 knockout mice are viable, but the adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain. Despite no global DNA methylation changes, 5mC levels are decreased at certain genomic loci in the brains of Uhrf2 knockout mice. Therefore, our study has revealed a unique role of UHRF2 in the maintenance of local 5mC levels in brain that is distinct from that of its paralog UHRF1. PMID:28402695

  2. An Abnormal Psychology Community Based Interview Assignment

    ERIC Educational Resources Information Center

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  3. Intrinsic spontaneous activity and subthreshold oscillations in neurones of the rat dorsal column nuclei in culture

    PubMed Central

    Reboreda, Antonio; Sánchez, Estela; Romero, Marcos; Lamas, J Antonio

    2003-01-01

    The basis of rhythmic activity observed at the dorsal column nuclei (DCN) is still open to debate. This study has investigated the electrophysiological properties of isolated DCN neurones deprived of any synaptic influence, using the perforated-patch technique. About half of the DCN neurones (64/130) were spontaneously active. More than half of the spontaneous neurones (36/64) showed a low threshold membrane oscillation (LTO) with a mean frequency of 11.4 Hz (range: 4.3–22.1 Hz, n = 20; I = 0). Cells showing LTOs also invariably showed a rhythmic 1.2 Hz clustering activity (groups of 2–5 action potentials separated by silent LTO periods). Also, more than one-third of the silent neurones presented clustering activity, always accompanied by LTOs, when slightly depolarised. The frequency of LTOs was voltage dependent and could be abolished by TTX (0.5 μM) and riluzole (30 μM), suggesting the participation of a sodium current. LTOs were also abolished by TEA (15 mM), which transformed clustering into tonic activity. In voltage clamp, most DCN neurones (85 %) showed a TTX-/riluzole-sensitive persistent sodium current (INa,p), which activated at about -60 mV and had a half-maximum activation at −49.8 mV. An M-like, non-inactivating outward current was present in 95 % of DCN neurones, and TEA (15 mM) inhibited this current by 73.7 %. The non-inactivating outward current was also inhibited by barium (1 mM) and linopirdine (10 μM), which suggests its M-like nature; both drugs failed to block the LTOs, but induced a reduction in their frequency by 56 and 20 %, respectively. These results demonstrate for the first time that DCN neurones have a complex and intrinsically driven clustering discharge pattern, accompanied by subthreshold membrane oscillations. Subthreshold oscillations rely on the interplay of a persistent sodium current and a non-inactivating TEA-sensitive outward current. PMID:12844503

  4. Relationship between auditory thresholds, central spontaneous activity and hair cell loss after acoustic trauma

    PubMed Central

    Mulders, W.H.A.M.; Ding, D.; Salvi, R.; Robertson, D.

    2011-01-01

    Acoustic trauma caused by exposure to a very loud sound increases spontaneous activity in central auditory structures such as the inferior colliculus. This hyperactivity has been suggested as a neural substrate for tinnitus, a phantom hearing sensation. In previous studies we have described a tentative link between the frequency region of hearing impairment and the corresponding tonotopic regions in the inferior colliculus showing hyperactivity. In this study we further investigated the relationship between cochlear compound action potential threshold loss, cochlear outer and inner hair cell loss and central hyperactivity in inferior colliculus of guinea pigs. Two weeks after a 10 kHz pure tone acoustic trauma, a tight relationship was demonstrated between the frequency region of compound action potential threshold loss and frequency regions in the inferior colliculus showing hyperactivity. Extending the duration of the acoustic trauma from 1 to 2 h did not result in significant increases in final cochlear threshold loss, but did result in a further increase of spontaneous firing rates in the inferior colliculus. Interestingly, hair cell loss was not present in the frequency regions where elevated cochlear thresholds and central hyperactivity were measured, suggesting that subtle changes in hair cell or primary afferent neural function are sufficient for central hyperactivity to be triggered and maintained. PMID:21491427

  5. Psychopathic traits associated with abnormal hemodynamic activity in salience and default mode networks during auditory oddball task.

    PubMed

    Anderson, Nathaniel E; Maurer, J Michael; Steele, Vaughn R; Kiehl, Kent A

    2018-06-01

    Psychopathy is a personality disorder accompanied by abnormalities in emotional processing and attention. Recent theoretical applications of network-based models of cognition have been used to explain the diverse range of abnormalities apparent in psychopathy. Still, the physiological basis for these abnormalities is not well understood. A significant body of work has examined psychopathy-related abnormalities in simple attention-based tasks, but these studies have largely been performed using electrocortical measures, such as event-related potentials (ERPs), and they often have been carried out among individuals with low levels of psychopathic traits. In this study, we examined neural activity during an auditory oddball task using functional magnetic resonance imaging (fMRI) during a simple auditory target detection (oddball) task among 168 incarcerated adult males, with psychopathic traits assessed via the Hare Psychopathy Checklist-Revised (PCL-R). Event-related contrasts demonstrated that the largest psychopathy-related effects were apparent between the frequent standard stimulus condition and a task-off, implicit baseline. Negative correlations with interpersonal-affective dimensions (Factor 1) of the PCL-R were apparent in regions comprising default mode and salience networks. These findings support models of psychopathy describing impaired integration across functional networks. They additionally corroborate reports which have implicated failures of efficient transition between default mode and task-positive networks. Finally, they demonstrate a neurophysiological basis for abnormal mobilization of attention and reduced engagement with stimuli that have little motivational significance among those with high psychopathic traits.

  6. Spontaneous acute spinal subdural hematoma: spontaneous recovery from severe paraparesis--case report and review.

    PubMed

    Payer, Michael; Agosti, Reto

    2010-11-01

    Spontaneous idiopathic acute spinal subdural hematomas are highly exceptional. Neurological symptoms are usually severe, and rapid diagnosis with MRI is mandatory. Surgical evacuation has frequently been used therapeutically; however, spontaneous recovery in mild cases has also been reported. We present a case of spontaneous recovery from severe paraparesis after spontaneous acute SSDH, and review the English-speaking literature.

  7. Recurrent abnormalities in conifer cones and the evolutionary origins of flower-like structures.

    PubMed

    Rudall, Paula J; Hilton, Jason; Vergara-Silva, Francisco; Bateman, Richard M

    2011-03-01

    Conifer cones are reproductive structures that are typically of restricted growth and either exclusively pollen-bearing (male) or exclusively ovule-bearing (female). Here, we review two common spontaneous developmental abnormalities of conifer cones: proliferated cones, in which the apex grows vegetatively, and bisexual cones, which possess both male and female structures. Emerging developmental genetic data, combined with evidence from comparative morphology, ontogeny and palaeobotany, provide new insights into the evolution of both cones and flowers, and prompt novel strategies for understanding seed-plant evolution. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Dynamic Brain Network Correlates of Spontaneous Fluctuations in Attention.

    PubMed

    Kucyi, Aaron; Hove, Michael J; Esterman, Michael; Hutchison, R Matthew; Valera, Eve M

    2017-03-01

    Human attention is intrinsically dynamic, with focus continuously shifting between elements of the external world and internal, self-generated thoughts. Communication within and between large-scale brain networks also fluctuates spontaneously from moment to moment. However, the behavioral relevance of dynamic functional connectivity and possible link with attentional state shifts is unknown. We used a unique approach to examine whether brain network dynamics reflect spontaneous fluctuations in moment-to-moment behavioral variability, a sensitive marker of attentional state. Nineteen healthy adults were instructed to tap their finger every 600 ms while undergoing fMRI. This novel, but simple, approach allowed us to isolate moment-to-moment fluctuations in behavioral variability related to attention, independent of common confounds in cognitive tasks (e.g., stimulus changes, response inhibition). Spontaneously increasing tap variance ("out-of-the-zone" attention) was associated with increasing activation in dorsal-attention and salience network regions, whereas decreasing tap variance ("in-the-zone" attention) was marked by increasing activation of default mode network (DMN) regions. Independent of activation, tap variance representing out-of-the-zone attention was also time-locked to connectivity both within DMN and between DMN and salience network regions. These results provide novel mechanistic data on the understudied neural dynamics of everyday, moment-to-moment attentional fluctuations, elucidating the behavioral importance of spontaneous, transient coupling within and between attention-relevant networks. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Cherubism with multiple dental abnormalities: a rare presentation

    PubMed Central

    Misra, Satya Ranjan; Mishra, Lora; Mohanty, Neeta; Mohanty, Susant

    2014-01-01

    Cherubism is a progressive, hereditary fibro-osseous lesion exclusively affecting the jaw bones. It is caused by the abnormal functioning of osteoblasts and osteoclasts, leading to replacement of normal bone by cellular fibrous tissue and immature bone, which produces painless progressive growth of the jaw, with a round facial appearance. It was first described in 1933 by Jones as ‘familial multilocular cystic disease of the jaws’. The term ‘cherubism’ was later coined to describe the rounded facial appearance resulting from jaw hypertrophy that was reminiscent of cherubs depicted throughout Renaissance art. The bony lesions generally occur at an early age, affect one or both jaws symmetrically, and grow progressively until puberty. Spontaneous regression is seen in most cases, although surgical re-contouring may be required for others for aesthetic reasons. PMID:25301429

  10. Abortive Spontaneous Egg Activation: An Emerging Biological Threat for the Existence of Mammals.

    PubMed

    Prasad, Shilpa; Tiwari, Meenakshi; Chaube, Shail K

    2017-06-01

    Mammals are important for balancing the natural ecosystem, but in the past few decades, several species have rapidly been entered under threatened category worldwide. The environmental changes, loss of natural habitats, human activities, and thereby stress are responsible for a gradual decline in reproductive outcome. Stress induces generation of reactive oxygen species (ROS). High physiological level of ROS drives abortive spontaneous egg activation (SEA), while beyond the physiological level causes oxidative stress (OS). The OS induces apoptosis and deteriorates egg quality that limits reproductive outcome. The reduced reproductive outcome is one of the major causes for gradual decline in population size of several mammalian species. Despite having several conservation programs, a gradual decline in species reproductive outcome and their population size is the serious concern for the existence of threatened mammalian species. Thus, it is important to identify and prevent the underlying causes responsible for abortive SEA, which could be an emerging problem for several mammalian species that are threatened or at the verge of extinction.

  11. A copy number variation genotyping method for aneuploidy detection in spontaneous abortion specimens.

    PubMed

    Chen, Songchang; Liu, Deyuan; Zhang, Junyu; Li, Shuyuan; Zhang, Lanlan; Fan, Jianxia; Luo, Yuqin; Qian, Yeqing; Huang, Hefeng; Liu, Chao; Zhu, Huanhuan; Jiang, Zhengwen; Xu, Chenming

    2017-02-01

    Chromosomal abnormalities such as aneuploidy have been shown to be responsible for causing spontaneous abortion. Genetic evaluation of abortions is currently underperformed. Screening for aneuploidy in the products of conception can help determine the etiology. We designed a high-throughput ligation-dependent probe amplification (HLPA) assay to examine aneuploidy of 24 chromosomes in miscarriage tissues and aimed to validate the performance of this technique. We carried out aneuploidy screening in 98 fetal tissue samples collected from female subjects with singleton pregnancies who experienced spontaneous abortion. The mean maternal age was 31.6 years (range: 24-43), and the mean gestational age was 10.2 weeks (range: 4.6-14.1). HLPA was performed in parallel with array comparative genomic hybridization, which is the gold standard for aneuploidy detection in clinical practices. The results from the two platforms were compared. Forty-nine out of ninety-eight samples were found to be aneuploid. HLPA showed concordance with array comparative genomic hybridization in diagnosing aneuploidy. High-throughput ligation-dependent probe amplification is a rapid and accurate method for aneuploidy detection. It can be used as a cost-effective screening procedure in clinical spontaneous abortions. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  12. GABA-A receptor antagonists increase firing, bursting and synchrony of spontaneous activity in neuronal networks grown on microelectrode arrays: a step towards chemical "fingerprinting"

    EPA Science Inventory

    Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical "fingerprints") could be used to classify chemical modes of action....

  13. CRISPR correction of the PRKAG2 gene mutation in the patient's induced pluripotent stem cell-derived cardiomyocytes eliminates electrophysiological and structural abnormalities.

    PubMed

    Ben Jehuda, Ronen; Eisen, Binyamin; Shemer, Yuval; Mekies, Lucy N; Szantai, Agnes; Reiter, Irina; Cui, Huanhuan; Guan, Kaomei; Haron-Khun, Shiraz; Freimark, Dov; Sperling, Silke R; Gherghiceanu, Mihaela; Arad, Michael; Binah, Ofer

    2018-02-01

    Mutations in the PRKAG2 gene encoding the γ-subunit of adenosine monophosphate kinase (AMPK) cause hypertrophic cardiomyopathy (HCM) and familial Wolff-Parkinson-White (WPW) syndrome. Patients carrying the R302Q mutation in PRKAG2 present with sinus bradycardia, escape rhythms, ventricular preexcitation, supraventricular tachycardia, and atrioventricular block. This mutation affects AMPK activity and increases glycogen storage in cardiomyocytes. The link between glycogen storage, WPW syndrome, HCM, and arrhythmias remains unknown. The purpose of this study was to investigate the pathological changes caused by the PRKAG2 mutation. We tested the hypothesis that patient's induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) display clinical aspects of the disease. Using clustered regularly interspaced short palindromic repeats (CRISPR) technology, we corrected the mutation and then generated isogenic iPSC-CMs. Action potentials were recorded from spontaneously firing and paced cardiomyocytes using the patch clamp technique. Using a microelectrode array setup, we recorded electrograms from iPSC-CMs clusters. Transmission electron microscopy was used to detect ultrastructural abnormalities in the mutated iPSC-CMs. PRKAG2-mutated iPSC-CMs exhibited abnormal firing patterns, delayed afterdepolarizations, triggered arrhythmias, and augmented beat rate variability. Importantly, CRISPR correction eliminated the electrophysiological abnormalities, the augmented glycogen, storage, and cardiomyocyte hypertrophy. PRKAG2-mutated iPSC-CMs displayed functional and structural abnormalities, which were abolished by correcting the mutation in the patient's iPSCs using CRISPR technology. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  14. Interprofessional learning, impression management, and spontaneity in the acute healthcare setting.

    PubMed

    Bell, Elaine; McAllister, Sue; Ward, Paul R; Russell, Alison

    2016-09-01

    Spontaneous learning is integral to definitions of interprofessional learning (IPL) because it has been suggested that spontaneous learning can be deeply connected with the work that people do in collaboration with colleagues via their professional networks. However, its nature and the processes involved are not well understood. Goffman's theory of impression management offers a useful theoretical framework to consider the way in which interaction in the workplace connects to spontaneous learning. This article explores the current literature to investigate the usefulness of this framework to better understand and identify spontaneous learning in the workplace. Aspects such as the connections between spontaneous learning occurring in formal and informal work activities, the spaces in which it occurs, and the influence of professional networking are considered. It is proposed that research directed to developing a better understanding of the nature of spontaneous learning in IPL will assist in connecting this learning to formal IPL curricula, enhancing IPL and patient outcomes.

  15. Abnormal Neural Progenitor Cells Differentiated from Induced Pluripotent Stem Cells Partially Mimicked Development of TSC2 Neurological Abnormalities.

    PubMed

    Li, Yaqin; Cao, Jiqing; Chen, Menglong; Li, Jing; Sun, Yiming; Zhang, Yu; Zhu, Yuling; Wang, Liang; Zhang, Cheng

    2017-04-11

    Tuberous sclerosis complex (TSC) is a disease featuring devastating and therapeutically challenging neurological abnormalities. However, there is a lack of specific neural progenitor cell models for TSC. Here, the pathology of TSC was studied using primitive neural stem cells (pNSCs) from a patient presenting a c.1444-2A>C mutation in TSC2. We found that TSC2 pNSCs had higher proliferative activity and increased PAX6 expression compared with those of control pNSCs. Neurons differentiated from TSC2 pNSCs showed enlargement of the soma, perturbed neurite outgrowth, and abnormal connections among cells. TSC2 astrocytes had increased saturation density and higher proliferative activity. Moreover, the activity of the mTOR pathway was enhanced in pNSCs and induced in neurons and astrocytes. Thus, our results suggested that TSC2 heterozygosity caused neurological malformations in pNSCs, indicating that its heterozygosity might be sufficient for the development of neurological abnormalities in patients. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  16. Ultrafast table-top dynamic radiography of spontaneous or stimulated events

    DOEpatents

    Smilowitz, Laura; Henson, Bryan

    2018-01-16

    Disclosed herein are representative embodiments of methods, apparatus, and systems for performing radiography. For example, certain embodiments concern X-ray radiography of spontaneous events. Particular embodiments of the disclosed technology provide continuous high-speed x-ray imaging of spontaneous dynamic events, such as explosions, reaction-front propagation, and even material failure. Further, in certain embodiments, x-ray activation and data collection activation are triggered by the object itself that is under observation (e.g., triggered by a change of state detected by one or more sensors monitoring the object itself).

  17. Effect of desipramine on spontaneous activity of hippocampal CA1 neuron after transient cerebral ischemia in rats.

    PubMed

    Zhu, Z T; Zhang, X X; Liu, J; Jin, G Z

    1996-01-01

    To study the spontaneous firing of CA1 neurons in rat hippocampus after transient cerebral ischemia and the effect of desipramine (Des) on the post-ischemic electric activity of CA1 neurons. Single-unit extracellular recordings were performed in rats on d 3 after 10 min of cerebral ischemia by occlusion of 4 arteries. Des and saline were injected into a tail vein. The histological changes of CA1 neurons was assessed by the neuronal density of the CA1 sector. The spontaneous firing rate of CA1 neurons on d 3 after ischemia was enhanced in comparison with the control value. Des (0.2 and 0.4 mg.kg-1, i.v., n = 5 & 6, respectively) reduced dose-dependently the increase of firing rate with maximal inhibition by 6 min (58% & 85%) to 9 min (69% & 94%) (vs vehicle group, P < 0.01). About 50% cells in CA1 region showed necrotic changes. Des antagonized the hyperexcitability of CA1 neurons after cerebral ischemia.

  18. Lysyl Oxidase Induces Vascular Oxidative Stress and Contributes to Arterial Stiffness and Abnormal Elastin Structure in Hypertension: Role of p38MAPK.

    PubMed

    Martínez-Revelles, Sonia; García-Redondo, Ana B; Avendaño, María S; Varona, Saray; Palao, Teresa; Orriols, Mar; Roque, Fernanda R; Fortuño, Ana; Touyz, Rhian M; Martínez-González, Jose; Salaices, Mercedes; Rodríguez, Cristina; Briones, Ana M

    2017-09-01

    Vascular stiffness, structural elastin abnormalities, and increased oxidative stress are hallmarks of hypertension. Lysyl oxidase (LOX) is an elastin crosslinking enzyme that produces H 2 O 2 as a by-product. We addressed the interplay between LOX, oxidative stress, vessel stiffness, and elastin. Angiotensin II (Ang II)-infused hypertensive mice and spontaneously hypertensive rats (SHR) showed increased vascular LOX expression and stiffness and an abnormal elastin structure. Mice over-expressing LOX in vascular smooth muscle cells (TgLOX) exhibited similar mechanical and elastin alterations to those of hypertensive models. LOX inhibition with β-aminopropionitrile (BAPN) attenuated mechanical and elastin alterations in TgLOX mice, Ang II-infused mice, and SHR. Arteries from TgLOX mice, Ang II-infused mice, and/or SHR exhibited increased vascular H 2 O 2 and O 2 .- levels, NADPH oxidase activity, and/or mitochondrial dysfunction. BAPN prevented the higher oxidative stress in hypertensive models. Treatment of TgLOX and Ang II-infused mice and SHR with the mitochondrial-targeted superoxide dismutase mimetic mito-TEMPO, the antioxidant apocynin, or the H 2 O 2 scavenger polyethylene glycol-conjugated catalase (PEG-catalase) reduced oxidative stress, vascular stiffness, and elastin alterations. Vascular p38 mitogen-activated protein kinase (p38MAPK) activation was increased in Ang II-infused and TgLOX mice and this effect was prevented by BAPN, mito-TEMPO, or PEG-catalase. SB203580, the p38MAPK inhibitor, normalized vessel stiffness and elastin structure in TgLOX mice. We identify LOX as a novel source of vascular reactive oxygen species and a new pathway involved in vascular stiffness and elastin remodeling in hypertension. LOX up-regulation is associated with enhanced oxidative stress that promotes p38MAPK activation, elastin structural alterations, and vascular stiffness. This pathway contributes to vascular abnormalities in hypertension. Antioxid. Redox Signal. 27

  19. Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art.

    PubMed

    Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

    2013-01-01

    Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience.

  20. Sculpting the Intrinsic Modular Organization of Spontaneous Brain Activity by Art

    PubMed Central

    Lin, Chia-Shu; Liu, Yong; Huang, Wei-Yuan; Lu, Chia-Feng; Teng, Shin; Ju, Tzong-Ching; He, Yong; Wu, Yu-Te; Jiang, Tianzi; Hsieh, Jen-Chuen

    2013-01-01

    Artistic training is a complex learning that requires the meticulous orchestration of sophisticated polysensory, motor, cognitive, and emotional elements of mental capacity to harvest an aesthetic creation. In this study, we investigated the architecture of the resting-state functional connectivity networks from professional painters, dancers and pianists. Using a graph-based network analysis, we focused on the art-related changes of modular organization and functional hubs in the resting-state functional connectivity network. We report that the brain architecture of artists consists of a hierarchical modular organization where art-unique and artistic form-specific brain states collectively mirror the mind states of virtuosos. We show that even in the resting state, this type of extraordinary and long-lasting training can macroscopically imprint a neural network system of spontaneous activity in which the related brain regions become functionally and topologically modularized in both domain-general and domain-specific manners. The attuned modularity reflects a resilient plasticity nurtured by long-term experience. PMID:23840527

  1. Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas

    PubMed Central

    Westermann, Frank; Muth, Daniel; Benner, Axel; Bauer, Tobias; Henrich, Kai-Oliver; Oberthuer, André; Brors, Benedikt; Beissbarth, Tim; Vandesompele, Jo; Pattyn, Filip; Hero, Barbara; König, Rainer; Fischer, Matthias; Schwab, Manfred

    2008-01-01

    Background Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype. In MYCN single-copy neuroblastomas, elevated MYCN mRNA and protein levels are paradoxically associated with a more favorable clinical phenotype, including disseminated tumors that subsequently regress spontaneously (stage 4s-non-amplified). In this study, we asked whether distinct transcriptional MYCN or c-MYC activities are associated with specific neuroblastoma phenotypes. Results We defined a core set of direct MYCN/c-MYC target genes by applying gene expression profiling and chromatin immunoprecipitation (ChIP, ChIP-chip) in neuroblastoma cells that allow conditional regulation of MYCN and c-MYC. Their transcript levels were analyzed in 251 primary neuroblastomas. Compared to localized-non-amplified neuroblastomas, MYCN/c-MYC target gene expression gradually increases from stage 4s-non-amplified through stage 4-non-amplified to MYCN amplified tumors. This was associated with MYCN activation in stage 4s-non-amplified and predominantly c-MYC activation in stage 4-non-amplified tumors. A defined set of MYCN/c-MYC target genes was induced in stage 4-non-amplified but not in stage 4s-non-amplified neuroblastomas. In line with this, high expression of a subset of MYCN/c-MYC target genes identifies a patient subtype with poor overall survival independent of the established risk markers amplified MYCN, disease stage, and age at diagnosis. Conclusions High MYCN/c-MYC target gene expression is a hallmark of malignant neuroblastoma progression, which is predominantly driven by c-MYC in stage 4-non-amplified tumors. In contrast, moderate MYCN function gain in stage 4s-non-amplified tumors induces only a restricted set of target genes that is still compatible with spontaneous regression. PMID:18851746

  2. Enhancement of oscillatory activity in the endopiriform nucleus of rats raised under abnormal oral conditions.

    PubMed

    Yoshimura, Hiroshi; Hasumoto-Honjo, Miho; Sugai, Tokio; Segami, Natsuki; Kato, Nobuo

    2014-02-21

    Endopiriform nucleus (EPN) is located deep to the piriform cortex, and has neural connections with not only neighboring sensory areas but also subcortical areas where emotional and nociceptive information is processed. Well-balanced oral condition might play an important role in stability of brain activities. When the oral condition is impaired, several areas in the brain might be affected. In the present study, we investigated whether abnormal conditions of oral region influence neural activities in the EPN. Orthodontic appliance that generates continuous force and chronic pain-related stress was fixed to maxillary incisors of rats, and raised. Field potential recordings were made from the EPN of brain slices. We previously reported that the EPN has an ability to generate membrane potential oscillation. In the present study, we have applied the same methods to assess activities of neuron clusters in the EPN. In the case of normal rats, stable field potential oscillations were induced in the EPN by application of low-frequency electrical stimulation under the medium with caffeine. In the case of rats with the orthodontic appliance, stable field potential oscillations were also induced, but both duration of oscillatory activities and wavelet number were increased. The enhanced oscillations were depressed by blockade of NMDA receptors. Thus, impairment of oral health under application of continuous orthodontic force and chronic pain-related stress enhanced neural activities in the EPN, in which up-regulation of NMDA receptors may be concerned. These findings suggest that the EPN might be involved in information processing with regard to abnormal conditions of oral region. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen.

    PubMed

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

    2013-02-01

    Glial calcium (Ca(2+)) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca(2+) waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O(2) tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca(2+) activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology.

  4. Starting and Stopping Spontaneous Family Conflicts.

    ERIC Educational Resources Information Center

    Vuchinich, Samuel

    1987-01-01

    Examined how 52 nondistressed families managed spontaneous verbal conflicts during family dinners. Found conflict initiation to be evenly distributed across family roles. Extension of conflict was constrained by constant probability of a next conflict move occurring. Most conflicts ended with no resolution. Mothers were most active in closing…

  5. Close pathological correlations between chronic kidney disease and reproductive organ-associated abnormalities in female cotton rats.

    PubMed

    Ichii, Osamu; Nakamura, Teppei; Irie, Takao; Kouguchi, Hirokazu; Sotozaki, Kozue; Horino, Taro; Sunden, Yuji; Elewa, Yaser Hosny Ali; Kon, Yasuhiro

    2018-03-01

    population has led to a concomitant age-related increase in chronic kidney disease. Moreover, the global prevalence of patients with chronic kidney disease is gradually increasing, which poses a serious public health problem. The limited number of spontaneous chronic kidney disease animal models, which resemble chronic kidney disease pathogenesis in elderly individuals, is a major limitation in the development of experimental and curative medicines for chronic kidney disease. This pathological study clarified that sex-related factors, including hormones, and abnormalities of the female reproductive system, such as pyometra, are closely associated with chronic kidney disease development by using cotton rats ( Sigmodon hispidus). Further, ovariectomy inhibited the phenotypes of the female reproductive system, immunological abnormalities, and chronic kidney disease. Thus, this laboratory rodent serves as a novel and useful spontaneous chronic kidney disease model to elucidate the candidate disease factors and the pathogenesis of chronic kidney disease both in human and experimental medicine.

  6. Caffeine depression of spontaneous activity in rabbit sino-atrial node cells.

    PubMed

    Satoh, H

    1993-05-01

    1. Effects of caffeine on the action potentials and the membrane currents in spontaneously beating rabbit sino-atrial (SA) node cells were examined using a two-microelectrode technique. 2. Cumulative administrations of caffeine (1-10 mM) caused a negative chronotropic effect in a concentration-dependent manner, which was not modified by atropine (0.1 microM). At 10 mM, caffeine increased the amplitude and prolonged the duration of action potentials significantly; the other parameters were unaffected. 3. In 3 of 16 preparations, caffeine (5 mM) elicited arrhythmia. At high Ca2+ (8.1 mM), caffeine (5 mM) increased the incidence of arrhythmia. 4. Caffeine (0.5-10 mM) enhanced the slow inward current, but at 10 mM decreased the enhanced peak current by 5 mM. The hyperpolarization-activated inward current was also enhanced by caffeine, but 10 mM caffeine decreased the current peak as compared with that at 5 mM. In addition, caffeine inhibited the delayed rectifying outward current in a concentration-dependent manner, accompanied by a depressed activation curve without any shift in the half-maximum activation voltage. 5. Caffeine elevated the cytoplasmic Ca2+ level in the SA node cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results suggest that caffeine enhances and/or inhibits the ionic currents and elicits arrhythmia due to the induction of cellular calcium overload.

  7. Cardiac abnormality prediction using HMLP network

    NASA Astrophysics Data System (ADS)

    Adnan, Ja'afar; Ahmad, K. A.; Mat, Muhamad Hadzren; Rizman, Zairi Ismael; Ahmad, Shahril

    2018-02-01

    Cardiac abnormality often occurs regardless of gender, age and races but depends on the lifestyle. This problem sometimes does not show any symptoms and usually detected once it already critical which lead to a sudden death to the patient. Basically, cardiac abnormality is the irregular electrical signal that generate by the pacemaker of the heart. This paper attempts to develop a program that can detect cardiac abnormality activity through implementation of Hybrid Multilayer Perceptron (HMLP) network. A certain amount of data of the heartbeat signals from the electrocardiogram (ECG) will be used in this project to train the MLP and HMLP network by using Modified Recursive Prediction Error (MRPE) algorithm and to test the network performance.

  8. On the spontaneous collective motion of active matter

    PubMed Central

    Wang, Shenshen; Wolynes, Peter G.

    2011-01-01

    Spontaneous directed motion, a hallmark of cell biology, is unusual in classical statistical physics. Here we study, using both numerical and analytical methods, organized motion in models of the cytoskeleton in which constituents are driven by energy-consuming motors. Although systems driven by small-step motors are described by an effective temperature and are thus quiescent, at higher order in step size, both homogeneous and inhomogeneous, flowing and oscillating behavior emerges. Motors that respond with a negative susceptibility to imposed forces lead to an apparent negative-temperature system in which beautiful structures form resembling the asters seen in cell division. PMID:21876141

  9. On the spontaneous collective motion of active matter.

    PubMed

    Wang, Shenshen; Wolynes, Peter G

    2011-09-13

    Spontaneous directed motion, a hallmark of cell biology, is unusual in classical statistical physics. Here we study, using both numerical and analytical methods, organized motion in models of the cytoskeleton in which constituents are driven by energy-consuming motors. Although systems driven by small-step motors are described by an effective temperature and are thus quiescent, at higher order in step size, both homogeneous and inhomogeneous, flowing and oscillating behavior emerges. Motors that respond with a negative susceptibility to imposed forces lead to an apparent negative-temperature system in which beautiful structures form resembling the asters seen in cell division.

  10. Abnormal gastrointestinal endocrine cells in patients with diabetes type 1: relationship to gastric emptying and myoelectrical activity.

    PubMed

    El-Salhy, M; Sitohy, B

    2001-11-01

    Gastrointestinal symptoms in patients with diabetes are believed to be caused by gastrointestinal dysmotility and secretion/absorption disturbances, and the gut endocrine cells play an important part in regulating these two functions. Studies on animal models of human diabetes type I revealed abnormality in these cells, but it is unknown whether abnormality also occurs in patients with diabetes. Eleven patients with long duration of diabetes type I and organ complications, as well as gastrointestinal symptoms, were studied. Endocrine cells in different segments of the gastrointestinal tract were detected by immunocytochemistry and quantified by computerized image analysis. Gastric emptying was measured by scintigraphy and gastric myoelectric activity was determined by electrogastrography. An abnormal density of gastrointestinal endocrine cells was found in patients with diabetes. This abnormality occurred in all segments of the upper and lower gastrointestinal tract investigated, and included most of the endocrine cell types. The patients showed delayed gastric emptying, which correlated closely with the acute glucose level, but did not correlate with HbA1c. Gastric emptying also correlated closely with the density of duodenal serotonin and secretin cells. The patients exhibited bradygastrias and tachygastrias. These dysrhythmias, however, did not differ significantly from controls. The endocrine cells are the anatomical units responsible for the production of gut hormones, and the change in their density would reflect a change in the capacity of producing these hormones. The abnormality in density of the gastrointestinal endocrine cells may contribute to the development of gastrointestinal dysmotility and the symptoms encountered in patients with diabetes.

  11. Detection of Cardiopulmonary Activity and Related Abnormal Events Using Microsoft Kinect Sensor.

    PubMed

    Al-Naji, Ali; Chahl, Javaan

    2018-03-20

    Monitoring of cardiopulmonary activity is a challenge when attempted under adverse conditions, including different sleeping postures, environmental settings, and an unclear region of interest (ROI). This study proposes an efficient remote imaging system based on a Microsoft Kinect v2 sensor for the observation of cardiopulmonary-signal-and-detection-related abnormal cardiopulmonary events (e.g., tachycardia, bradycardia, tachypnea, bradypnea, and central apnoea) in many possible sleeping postures within varying environmental settings including in total darkness and whether the subject is covered by a blanket or not. The proposed system extracts the signal from the abdominal-thoracic region where cardiopulmonary activity is most pronounced, using a real-time image sequence captured by Kinect v2 sensor. The proposed system shows promising results in any sleep posture, regardless of illumination conditions and unclear ROI even in the presence of a blanket, whilst being reliable, safe, and cost-effective.

  12. Detection of Cardiopulmonary Activity and Related Abnormal Events Using Microsoft Kinect Sensor

    PubMed Central

    Chahl, Javaan

    2018-01-01

    Monitoring of cardiopulmonary activity is a challenge when attempted under adverse conditions, including different sleeping postures, environmental settings, and an unclear region of interest (ROI). This study proposes an efficient remote imaging system based on a Microsoft Kinect v2 sensor for the observation of cardiopulmonary-signal-and-detection-related abnormal cardiopulmonary events (e.g., tachycardia, bradycardia, tachypnea, bradypnea, and central apnoea) in many possible sleeping postures within varying environmental settings including in total darkness and whether the subject is covered by a blanket or not. The proposed system extracts the signal from the abdominal-thoracic region where cardiopulmonary activity is most pronounced, using a real-time image sequence captured by Kinect v2 sensor. The proposed system shows promising results in any sleep posture, regardless of illumination conditions and unclear ROI even in the presence of a blanket, whilst being reliable, safe, and cost-effective. PMID:29558414

  13. Relationship between individual neuron and network spontaneous activity in developing mouse cortex.

    PubMed

    Barnett, Heather M; Gjorgjieva, Julijana; Weir, Keiko; Comfort, Cara; Fairhall, Adrienne L; Moody, William J

    2014-12-15

    Spontaneous synchronous activity (SSA) that propagates as electrical waves is found in numerous central nervous system structures and is critical for normal development, but the mechanisms of generation of such activity are not clear. In previous work, we showed that the ventrolateral piriform cortex is uniquely able to initiate SSA in contrast to the dorsal neocortex, which participates in, but does not initiate, SSA (Lischalk JW, Easton CR, Moody WJ. Dev Neurobiol 69: 407-414, 2009). In this study, we used Ca(2+) imaging of cultured embryonic day 18 to postnatal day 2 coronal slices (embryonic day 17 + 1-4 days in culture) of the mouse cortex to investigate the different activity patterns of individual neurons in these regions. In the piriform cortex where SSA is initiated, a higher proportion of neurons was active asynchronously between waves, and a larger number of groups of coactive cells was present compared with the dorsal cortex. When we applied GABA and glutamate synaptic antagonists, asynchronous activity and cellular clusters remained, while synchronous activity was eliminated, indicating that asynchronous activity is a result of cell-intrinsic properties that differ between these regions. To test the hypothesis that higher levels of cell-autonomous activity in the piriform cortex underlie its ability to initiate waves, we constructed a conductance-based network model in which three layers differed only in the proportion of neurons able to intrinsically generate bursting behavior. Simulations using this model demonstrated that a gradient of intrinsic excitability was sufficient to produce directionally propagating waves that replicated key experimental features, indicating that the higher level of cell-intrinsic activity in the piriform cortex may provide a substrate for SSA generation. Copyright © 2014 the American Physiological Society.

  14. Spontaneous triadic engagement in bonobos (Pan paniscus) and chimpanzees (Pan troglodytes).

    PubMed

    MacLean, Evan; Hare, Brian

    2013-08-01

    Humans are believed to have evolved a unique motivation to participate in joint activities that first develops during infancy and supports the development of shared intentionality. We conducted five experiments with bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) (Total n = 119) to assess their motivation to spontaneously participate in joint activities with a conspecific or a human. We found that even the youngest subjects preferred to interact together with a human and a toy rather than engaging in an identical game alone. In addition, we found that subjects could spontaneously interact with a human in a turn-taking game involving passing a ball back and forth and used behaviors to elicit additional interaction when the game was disrupted. However, when paired with a conspecific, subjects preferred to interact with an object individually rather than together. Our results indicate that nonhuman apes are motivated to engage in triadic activities if they occur spontaneously with humans and require a minimum amount of coordination. These findings leave open the question of whether these activities are coordinated through shared intentions.

  15. Fetal Heart Rate Monitoring During Surgical Correction of Spontaneous Pneumothorax During Pregnancy: Lessons in In Utero Resuscitation.

    PubMed

    Wilson, Bailey; Burt, Bryan; Baker, Byron; Clark, Steven L; Belfort, Michael; Gandhi, Manisha

    2016-01-01

    Spontaneous pneumothorax during pregnancy has potentially serious implications for the mother and fetus. When surgical correction is required, complex maternal physiologic alterations may significantly affect fetal well-being. A woman underwent thoracoscopic lung resection and pleurodesis at 29 weeks of gestation. At various points during the procedure, maternal hemodynamic and respiratory consequences of anesthetic and surgical management resulted in severe fetal heart rate (FHR) decelerations and bradycardia. In each instance, physiologic manipulations based on an understanding of the likely cause of fetal hypoxia allowed correction of the FHR abnormalities without delivery. Nonsurgical perinatal intervention based on FHR monitoring and analysis of the likely pathophysiologic abnormalities underlying fetal decelerations may allow the gravid woman to undergo complex procedures and continue the pregnancy.

  16. Abnormal Magnetic Field Effects on Electrogenerated Chemiluminescence

    NASA Astrophysics Data System (ADS)

    Pan, Haiping; Shen, Yan; Wang, Hongfeng; He, Lei; Hu, Bin

    2015-03-01

    We report abnormal magnetic field effects on electrogenerated chemiluminescence (MFEECL) based on triplet emission from the Ru(bpy)3Cl2-TPrA electrochemical system: the appearance of MFEECL after magnetic field ceases. In early studies the normal MFEECL have been observed from electrochemical systems during the application of magnetic field. Here, the abnormal MFEECL suggest that the activated charge-transfer [Ru(bpy)33+ … TPrA•] complexes may become magnetized in magnetic field and experience a long magnetic relaxation after removing magnetic field. Our analysis indicates that the magnetic relaxation can gradually increase the density of charge-transfer complexes within reaction region due to decayed magnetic interactions, leading to a positive component in the abnormal MFEECL. On the other hand, the magnetic relaxation facilitates an inverse conversion from triplets to singlets within charge-transfer complexes. The inverse triplet --> singlet conversion reduces the density of triplet light-emitting states through charge-transfer complexes and gives rise to a negative component in the abnormal MFEECL. The combination of positive and negative components can essentially lead to a non-monotonic profile in the abnormal MFEECL after ceasing magnetic field. Nevertheless, our experimental studies may reveal un-usual magnetic behaviors with long magnetic relaxation from the activated charge-transfer [Ru(bpy)33+ … TPrA•] complexes in solution at room temperature.

  17. Changes in Brain Activation Associated with Spontaneous Improvization and Figural Creativity After Design-Thinking-Based Training: A Longitudinal fMRI Study.

    PubMed

    Saggar, Manish; Quintin, Eve-Marie; Bott, Nicholas T; Kienitz, Eliza; Chien, Yin-Hsuan; Hong, Daniel W-C; Liu, Ning; Royalty, Adam; Hawthorne, Grace; Reiss, Allan L

    2017-07-01

    Creativity is widely recognized as an essential skill for entrepreneurial success and adaptation to daily-life demands. However, we know little about the neural changes associated with creative capacity enhancement. For the first time, using a prospective, randomized control design, we examined longitudinal changes in brain activity associated with participating in a five-week design-thinking-based Creative Capacity Building Program (CCBP), when compared with Language Capacity Building Program (LCBP). Creativity, an elusive and multifaceted construct, is loosely defined as an ability to produce useful/appropriate and novel outcomes. Here, we focus on one of the facets of creative thinking-spontaneous improvization. Participants were assessed pre- and post-intervention for spontaneous improvization skills using a game-like figural Pictionary-based fMRI task. Whole-brain group-by-time interaction revealed reduced task-related activity in CCBP participants (compared with LCBP participants) after training in the right dorsolateral prefrontal cortex, anterior/paracingulate gyrus, supplementary motor area, and parietal regions. Further, greater cerebellar-cerebral connectivity was observed in CCBP participants at post-intervention when compared with LCBP participants. In sum, our results suggest that improvization-based creative capacity enhancement is associated with reduced engagement of executive functioning regions and increased involvement of spontaneous implicit processing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Dynamic exercise training prevents exercise pressor reflex overactivity in spontaneously hypertensive rats

    PubMed Central

    Iwamoto, Gary A.; Vongpatanasin, Wanpen; Mitchell, Jere H.; Smith, Scott A.

    2015-01-01

    Cardiovascular responses to exercise are exaggerated in hypertension. We previously demonstrated that this heightened cardiovascular response to exercise is mediated by an abnormal skeletal muscle exercise pressor reflex (EPR) with important contributions from its mechanically and chemically sensitive components. Exercise training attenuates exercise pressor reflex function in healthy subjects as well as in heart failure rats. However, whether exercise training has similar physiological benefits in hypertension remains to be elucidated. Thus we tested the hypothesis that the EPR overactivity manifest in hypertension is mitigated by exercise training. Changes in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in response to muscle contraction, passive muscle stretch, and hindlimb intra-arterial capsaicin administration were examined in untrained normotensive Wistar-Kyoto rats (WKYUT; n = 6), exercise-trained WKY (WKYET; n = 7), untrained spontaneously hypertensive rats (SHRUT; n = 8), and exercise-trained SHR (SHRET; n = 7). Baseline MAP after decerebration was significantly decreased by 3 mo of wheel running in SHRET (104 ± 9 mmHg) compared with SHRUT (125 ± 10 mmHg). As previously reported, the pressor and renal sympathetic responses to muscle contraction, stretch, and capsaicin administration were significantly higher in SHRUT than WKYUT. Exercise training significantly attenuated the enhanced contraction-induced elevations in MAP (SHRUT: 53 ± 11 mmHg; SHRET: 19 ± 3 mmHg) and RSNA (SHRUT: 145 ± 32%; SHRET: 57 ± 11%). Training produced similar attenuating effects in SHR during passive stretch and capsaicin administration. These data demonstrate that the abnormally exaggerated EPR function that develops in hypertensive rats is significantly diminished by exercise training. PMID:26163445

  19. Spontaneous Anterior Lens Capsule Rupture Of a Patient with Alport Syndrome - A Case Report.

    PubMed

    Trifonova, Kalina; Jordanoff, George; Stoyanov, Valentin; Slaveykov, Kiril

    2017-12-15

    Alport syndrome is a progressive genetic disease which is characterised by glomerulonephritis, sensorineural deafness and ocular abnormalities. We aimed to present a clinical case of a patient with Alport syndrome with spontaneous anterior lens capsule rupture. A 16-year-old male with histologically proven Alport syndrome was hospitalised in the Department of Ophthalmology, University Hospital "Prof. Stoyan Kirkovich", Stara Zagora with low vision, pain, redness, high IOP and rupture of the anterior lenticular capsule of the right eye. Phacoaspiration was successfully performed (Millenium, Bausch& Lomb, Rochester, New York, USA) with the bimanual irrigation-aspiration system (Geuder AG, Heidelberg, Germany) with excellent visual results. As the syndrome is quite rare and can lead to diagnostic difficulties for the ophthalmologist complications such as spontaneous or traumatic rupture of the capsule are not uncommon. In such cases, phacoaspiration is an efficient method for clear lens extraction after ruptures of the anterior lenticular capsule of young patients with Alport syndrome.

  20. Neural substrates of spontaneous musical performance: an FMRI study of jazz improvisation.

    PubMed

    Limb, Charles J; Braun, Allen R

    2008-02-27

    To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity.

  1. Spontaneous Oscillation by Hair Bundles of the Bullfrog's Sacculus

    PubMed Central

    Martin, Pascal; Bozovic, D.; Choe, Y.; Hudspeth, A. J.

    2007-01-01

    One prominent manifestation of mechanical activity in hair cells is spontaneous otoacoustic emission, the unprovoked emanation of sound by an internal ear. Because active hair-bundle motility probably constitutes the active process of non-mammalian hair cells, we investigated the ability of hair bundles in the bullfrog's sacculus to produce oscillations that might underlie spontaneous otoacoustic emissions. When maintained in the ear's normal ionic milieu, many bundles oscillated spontaneously through distances as great as 80 nm at frequencies of 5-50 Hz. Whole-cell recording disclosed that the positive phase of movement was associated with the opening of transduction channels. Gentamicin, which blocks transduction channels, reversibly arrested oscillation; drugs that affect the cAMP phosphorylation pathway and might influence myosin's activity altered the rate of oscillation. Increasing the Ca2+ concentration rendered oscillations faster and smaller until they were suppressed; lowering the Ca2+ concentration moderately with chelators had the opposite effect. When a bundle was offset with a stimulus fiber, oscillations were transiently suppressed but gradually resumed. Loading a bundle by partial displacement clamping, which simulated the presence of the accessory structures to which a bundle is ordinarily attached, increased the frequency and diminished the magnitude of oscillation. These observations accord with a model in which oscillations arise from the interplay of the hair bundle's negative stiffness with the activity of adaptation motors and with Ca2+-dependent relaxation of gating springs. PMID:12805294

  2. Reduced spontaneous but relatively normal deliberate vicarious representations in psychopathy

    PubMed Central

    Meffert, Harma; Gazzola, Valeria; den Boer, Johan A.; Bartels, Arnold A. J.

    2013-01-01

    Psychopathy is a personality disorder associated with a profound lack of empathy. Neuroscientists have associated empathy and its interindividual variation with how strongly participants activate brain regions involved in their own actions, emotions and sensations while viewing those of others. Here we compared brain activity of 18 psychopathic offenders with 26 control subjects while viewing video clips of emotional hand interactions and while experiencing similar interactions. Brain regions involved in experiencing these interactions were not spontaneously activated as strongly in the patient group while viewing the video clips. However, this group difference was markedly reduced when we specifically instructed participants to feel with the actors in the videos. Our results suggest that psychopathy is not a simple incapacity for vicarious activations but rather reduced spontaneous vicarious activations co-existing with relatively normal deliberate counterparts. PMID:23884812

  3. Spontaneous abortion and recurrent miscarriage: A comparison of cytogenetic diagnosis in 250 cases.

    PubMed

    Choi, Tae Yeong; Lee, Hye Min; Park, Won Kyoung; Jeong, So Yeong; Moon, Hwa Sook

    2014-11-01

    The purpose of this study was to determine the frequency and distribution of cytogenetically abnormal miscarriages in couples with spontaneous abortions (SA) or recurrent miscarriages (RM). Karyotyping of specimens from 164 abortuses with SA and 86 abortuses with RM was successfully performed according to the standard cytogenetic methods using G-banding technique. Among the total 164 cases of SA group, 81 (49.4%) were euploid and the rest (83, 50.6%) showed chromosomal abnormalities. In RM(≥2) and RM(≥3) group, 31 (36.0%)/27 (34.6%) cases were euploid and 55 (64.0%)/51(65.4%) cases were abnormal, respectively. A statistically significant difference was found in the rate of cytogenetic abnormality between SA and RM groups (P<0.05). In all groups, women with advanced maternal age (≥35 years) had a higher rate of chromosome anomalies compared with women younger than age 35 (normal:abnormal = 32.4%:67.6% for ≥35 years and 53.8%:46.2% for <35 years in SA; 19.2%:80.8%/21.7%:78.3% for ≥35 years and 43.3%:56.7%/40.0%:60.0% for <35 years in RM(≥2) and RM(≥3), respectively; P<0.05). In SA group, an increase of normal karyotypes was noted with increased gestational age (<10 week, 38.0%; 10-15 week, 53.5%; 16-20 week, 65.7%). In RM group, most of cases were in <10 week and the frequency of trisomies with chromosomes 1 to 10 were increased compared with that of SA. There was a statistically significant difference in the frequency and distribution of chromosomal abnormalities between SA and RM groups. Our results will provide useful information for diagnosis and genetic counseling of patients with SA or RM.

  4. Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women.

    PubMed Central

    Rosenstein, I J; Morgan, D J; Lamont, R F; Sheehan, M; Doré, C J; Hay, P E; Taylor-Robinson, D

    2000-01-01

    OBJECTIVES: To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. METHODS: A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. RESULTS: Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. CONCLUSIONS: Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen. PMID:10968599

  5. Effect of intravaginal clindamycin cream on pregnancy outcome and on abnormal vaginal microbial flora of pregnant women.

    PubMed

    Rosenstein, I J; Morgan, D J; Lamont, R F; Sheehan, M; Doré, C J; Hay, P E; Taylor-Robinson, D

    2000-01-01

    To determine whether intravaginal clindamycin cream reduces the incidence of abnormal pregnancy outcome in women with abnormal vaginal microbial flora graded as intermediate or BV and to investigate the effect of the antibiotic on vaginal microbial flora. A prospective cohort study of pregnant women in an antenatal clinic of a district general hospital. The subjects were 268 women who had abnormal vaginal microbial flora at first clinic visit by examination of a Gram-stained vaginal smear and 34 women with a normal vaginal flora. Two hundred and thirty-seven women were evaluable. Women with abnormal Gram-stained smears (graded as II or III) on clinic recall were randomised to receive treatment (intravaginal clindamycin cream) or placebo and followed to assess outcome of pregnancy, vaginal flora, and detection of Mycoplasma hominis and Ureaplasma urealyticum after treatment. Abnormal outcomes of pregnancy were not significantly different in treated and placebo groups by Chi square (P = 0.2). However, women with grade III flora responded better to clindamycin than women with grade II flora by numbers of abnormal outcomes (P = 0.03) and return to normal vaginal flora (P = 0.01) (logistic regression analysis model). This may be due to differences in vaginal bacterial species in these grades. Women whose abnormal vaginal flora had spontaneously returned to normal on follow-up and were therefore not treated (revertants) had as many abnormal outcomes as placebos suggesting that damage by abnormal bacterial species occurred early in pregnancy. Gram-stain screening distinguishing grade II from grade III flora may be helpful in prescribing treatment other than clindamycin for women with grade II flora. Earlier diagnosis and treatment may be more effective in preventing an abnormal outcome, possibly as soon as pregnancy is diagnosed or even offered as a pre-conception screen.

  6. Photonic Crystals-Inhibited Spontaneous Emission: Optical Antennas-Enhanced Spontaneous Emission

    NASA Astrophysics Data System (ADS)

    Yablonovitch, Eli

    Photonic crystals are also part of everyday technological life in opto-electronic telecommunication devices that provide us with internet, cloud storage, and email. But photonic crystals have also been identified in nature, in the coloration of peacocks, parrots, chameleons, butterflies and many other species.In spite of its broad applicability, the original motivation of photonic crystals was to create a ``bandgap'' in which the spontaneous emission of light would be inhibited. Conversely, the opposite is now possible. The ``optical antenna'' can accelerate spontaneous emission. Over 100 years after the radio antenna, we finally have tiny ``optical antennas'' which can act on molecules and quantum dots. Employing optical antennas, spontaneous light emission can become faster than stimulated emission.

  7. Low doses of alcohol potentiate GABA sub B inhibition of spontaneous activity of hippocampal CA1 neurons in vivo

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Criado, J.R.; Thies, R.

    1991-03-11

    Low doses of alcohol facilitate firing of hippocampal neurons. Such doses also enhance the inhibitory actions of GABA. Alcohol is known to potentiate inhibition via GABA{sub A} receptors. However, the effects of alcohol on GABA{sub B} receptor function are not understood. Spontaneous activity of single units was recorded from CA1 neurons of male rats anesthetized with 1.0% halothane. Electrical recordings and local application of drugs were done with multi-barrel pipettes. CA1 pyramidal neurons fired spontaneous bursts of action potentials. Acute alcohol decreased the interval between bursts, a mild excitatory action. Alcohol also more than doubled the period of complete inhibitionmore » produced by local application of both GABA and baclofen. These data suggest that GABA{sub B}-mediated inhibition is also potentiated by low doses of alcohol.« less

  8. Spontaneous calcium waves in Bergman glia increase with age and hypoxia and may reduce tissue oxygen

    PubMed Central

    Mathiesen, Claus; Brazhe, Alexey; Thomsen, Kirsten; Lauritzen, Martin

    2013-01-01

    Glial calcium (Ca2+) waves constitute a means to spread signals between glial cells and to neighboring neurons and blood vessels. These waves occur spontaneously in Bergmann glia (BG) of the mouse cerebellar cortex in vivo. Here, we tested three hypotheses: (1) aging and reduced blood oxygen saturation alters wave activity; (2) glial Ca2+ waves change cerebral oxygen metabolism; and (3) neuronal and glial wave activity is correlated. We used two-photon microscopy in the cerebellar cortexes of adult (8- to 15-week-old) and aging (48- to 80-week-old) ketamine-anesthetized mice after bolus loading with OGB-1/AM and SR101. We report that the occurrence of spontaneous waves is 20 times more frequent in the cerebellar cortex of aging as compared with adult mice, which correlated with a reduction in resting brain oxygen tension. In adult mice, spontaneous glial wave activity increased on reducing resting brain oxygen tension, and ATP-evoked glial waves reduced the tissue O2 tension. Finally, although spontaneous Purkinje cell (PC) activity was not associated with increased glia wave activity, spontaneous glial waves did affect intracellular Ca2+ activity in PCs. The increased wave activity during aging, as well as low resting brain oxygen tension, suggests a relationship between glial waves, brain energy homeostasis, and pathology. PMID:23211964

  9. Enlargement of Ribbons in Zebrafish Hair Cells Increases Calcium Currents But Disrupts Afferent Spontaneous Activity and Timing of Stimulus Onset

    PubMed Central

    Schreck, Mary; Petralia, Ronald S.; Wang, Ya-Xian; Zhang, Qiuxiang

    2017-01-01

    In sensory hair cells of auditory and vestibular organs, the ribbon synapse is required for the precise encoding of a wide range of complex stimuli. Hair cells have a unique presynaptic structure, the synaptic ribbon, which organizes both synaptic vesicles and calcium channels at the active zone. Previous work has shown that hair-cell ribbon size is correlated with differences in postsynaptic activity. However, additional variability in postsynapse size presents a challenge to determining the specific role of ribbon size in sensory encoding. To selectively assess the impact of ribbon size on synapse function, we examined hair cells in transgenic zebrafish that have enlarged ribbons, without postsynaptic alterations. Morphologically, we found that enlarged ribbons had more associated vesicles and reduced presynaptic calcium-channel clustering. Functionally, hair cells with enlarged ribbons had larger global and ribbon-localized calcium currents. Afferent neuron recordings revealed that hair cells with enlarged ribbons resulted in reduced spontaneous spike rates. Additionally, despite larger presynaptic calcium signals, we observed fewer evoked spikes with longer latencies from stimulus onset. Together, our work indicates that hair-cell ribbon size influences the spontaneous spiking and the precise encoding of stimulus onset in afferent neurons. SIGNIFICANCE STATEMENT Numerous studies support that hair-cell ribbon size corresponds with functional sensitivity differences in afferent neurons and, in the case of inner hair cells of the cochlea, vulnerability to damage from noise trauma. Yet it is unclear whether ribbon size directly influences sensory encoding. Our study reveals that ribbon enlargement results in increased ribbon-localized calcium signals, yet reduces afferent spontaneous activity and disrupts the timing of stimulus onset, a distinct aspect of auditory and vestibular encoding. These observations suggest that varying ribbon size alone can influence

  10. Drug-induced modification of the system properties associated with spontaneous human electroencephalographic activity

    NASA Astrophysics Data System (ADS)

    Liley, David T.; Cadusch, Peter J.; Gray, Marcus; Nathan, Pradeep J.

    2003-11-01

    The benzodiazepine (BZ) class of minor tranquilizers are important modulators of the γ-amino butyric acid (GABAA)/BZ receptor complex that are well known to affect the spectral properties of spontaneous electroencephalographic activity. While it is experimentally well established that the BZs reduce total alpha band (8 13 Hz) power and increase total beta band (13 30 Hz) power, it is unclear what the physiological basis for this effect is. Based on a detailed theory of cortical electrorhythmogenesis it is conjectured that such an effect is explicable in terms of the modulation of GABAergic neurotransmission within locally connected populations of excitatory and inhibitory cortical neurons. Motivated by this theory, fixed order autoregressive moving average (ARMA) models were fitted to spontaneous eyes-closed electroencephalograms recorded from subjects before and approximately 2 h after the oral administration of a single 1 mg dose of the BZ alprazolam. Subsequent pole-zero analysis revealed that BZs significantly transform the dominant system pole such that its frequency and damping increase. Comparisons of ARMA derived power spectra with fast Fourier transform derived spectra indicate an enhanced ability to identify benzodiazepine induced electroencephalographic changes. This experimental result is in accord with the theoretical predictions implying that alprazolam enhances inhibition acting on inhibitory neurons more than inhibition acting on excitatory neurons. Further such a result is consistent with reported cortical neuronal distributions of the various GABAA receptor pharmacological subtypes. Therefore physiologically specified fixed order ARMA modeling is expected to become an important tool for the systematic investigation and modeling of a wide range of cortically acting compounds.

  11. Non-traumatic spontaneous acute epidural hematoma in a patient with sickle cell disease.

    PubMed

    Serarslan, Yurdal; Aras, Mustafa; Altaş, Murat; Kaya, Hasan; Urfalı, Boran

    2014-01-01

    A 19-year-old female with sickle cell anemia (SCD) was referred to our hospital after two days of hospitalization at another hospital for a headache crisis. This headache crisis was due to a raised intracranial pressure; these symptoms were noted and included in her comprehensive list of symptoms. There was an acute drop in the hemoglobin and hematocrit levels. The cranial CT scan demonstrated a left fronto-parietal acute epidural hematoma (AEH) and a calvarial bone expansion, which was suggestive of medullary hematopoiesis. The patient underwent emergent craniotomy and evacuation of the hematoma. There were no abnormal findings intra-operatively apart from the AEH, except skull thickening and active petechial bleeding from the dural arteries. Repeated CT scan showed a complete evacuation of the hematoma. The possible underlying pathophysiological mechanisms were discussed. In addition to the factors mentioned in the relevant literature, any active petechial bleeding from the dural arteries on the separated surface of the dura from the skull could have contributed to the expanding of the AEH in our patient. Neurosurgeons and other health care providers should be aware of spontaneous AEH in patients with SCD. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  12. Abnormal mTOR Activation in Autism.

    PubMed

    Winden, Kellen D; Ebrahimi-Fakhari, Darius; Sahin, Mustafa

    2018-01-25

    The mechanistic target of rapamycin (mTOR) is an important signaling hub that integrates environmental information regarding energy availability and stimulates anabolic molecular processes and cell growth. Abnormalities in this pathway have been identified in several syndromes in which autism spectrum disorder (ASD) is highly prevalent. Several studies have investigated mTOR signaling in developmental and neuronal processes that, when dysregulated, could contribute to the development of ASD. Although many potential mechanisms still remain to be fully understood, these associations are of great interest because of the clinical availability of mTOR inhibitors. Clinical trials evaluating the efficacy of mTOR Expected final online publication date for the Annual Review of Neuroscience Volume 41 is July 8, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  13. Effect of Changing the Joint Kinematics of Knees With a Ruptured Anterior Cruciate Ligament on the Molecular Biological Responses and Spontaneous Healing in a Rat Model.

    PubMed

    Kokubun, Takanori; Kanemura, Naohiko; Murata, Kenji; Moriyama, Hideki; Morita, Sadao; Jinno, Tetsuya; Ihara, Hidetoshi; Takayanagi, Kiyomi

    2016-11-01

    The poor healing capacity of a completely ruptured anterior cruciate ligament (ACL) has been attributed to an insufficient vascular supply, cellular metabolism, and deficient premature scaffold formation because of the unique intra-articular environment. However, previous studies have focused on intra-articular factors without considering extra-articular factors, including the biomechanical aspects of ACL-deficient knees. Changing the joint kinematics of an ACL-ruptured knee will improve cellular biological responses and lead to spontaneous healing through the mechanotransduction mechanism. Controlled laboratory study. A total of 66 skeletally mature Wistar rats were randomly assigned to a sham-operated group (SO), ACL-transection group (ACL-T), controlled abnormal movement group (CAM), and an intact group (IN). The ACL was completely transected at the midportion in the ACL-T and CAM groups, and the CAM group underwent extra-articular braking to control for abnormal tibial translation. The SO group underwent skin and joint capsule incisions and tibial drilling, without ACL transection and extra-articular braking. The animals were allowed full cage activity until sacrifice at 1, 2, 4, 6, and 8 weeks postoperatively for histological, molecular biological, and biomechanical assessment. All injured ACLs in the ACL-T group were not healed, but those in the CAM group healed spontaneously, showing a typical ligament healing response. Regarding the molecular biological response, there was an upregulation of anabolic factors (ie, transforming growth factor-β) and downregulation of catabolic factors (ie, matrix metalloproteinase). Examination of the mechanical properties at 8 weeks after injury showed that >50% of the strength of the intact ACL had returned. Our results suggest that changing the joint kinematics of knees with a ruptured ACL alters the molecular biological responses and leads to spontaneous healing. These data support our hypothesis that the

  14. Early Activation of Ventral Hippocampus and Subiculum during Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

    PubMed Central

    Toyoda, Izumi; Bower, Mark R.; Leyva, Fernando

    2013-01-01

    Temporal lobe epilepsy is the most common form of epilepsy in adults. The pilocarpine-treated rat model is used frequently to investigate temporal lobe epilepsy. The validity of the pilocarpine model has been challenged based largely on concerns that seizures might initiate in different brain regions in rats than in patients. The present study used 32 recording electrodes per rat to evaluate spontaneous seizures in various brain regions including the septum, dorsomedial thalamus, amygdala, olfactory cortex, dorsal and ventral hippocampus, substantia nigra, entorhinal cortex, and ventral subiculum. Compared with published results from patients, seizures in rats tended to be shorter, spread faster and more extensively, generate behavioral manifestations more quickly, and produce generalized convulsions more frequently. Similarities to patients included electrographic waveform patterns at seizure onset, variability in sites of earliest seizure activity within individuals, and variability in patterns of seizure spread. Like patients, the earliest seizure activity in rats was recorded most frequently within the hippocampal formation. The ventral hippocampus and ventral subiculum displayed the earliest seizure activity. Amygdala, olfactory cortex, and septum occasionally displayed early seizure latencies, but not above chance levels. Substantia nigra and dorsomedial thalamus demonstrated consistently late seizure onsets, suggesting their unlikely involvement in seizure initiation. The results of the present study reveal similarities in onset sites of spontaneous seizures in patients with temporal lobe epilepsy and pilocarpine-treated rats that support the model's validity. PMID:23825415

  15. Spontaneous voltage and current fluctuations in tissue cultured mouse dorsal root ganglion cells.

    PubMed

    Mathers, D A; Barker, J L

    1984-02-13

    Fetal mouse dorsal root ganglion (DRG) neurons were maintained in primary dissociated cell culture for periods of 7 days to 3 months. Intracellular recordings from these cells revealed the presence of spontaneous subthreshold potentials in 101/177 neurons studied. When measured at the resting membrane potential, these spontaneous voltage events took two forms: (a) high frequency potential fluctuations several millivolts in peak-to-peak amplitude and (b) small, discrete hyperpolarizations. Neurons exhibiting either type of event were designated as 'active' DRG cells. No spontaneous potentials were seen in DRG cells hyperpolarized to membrane voltages more negative than -64 +/- 11.5 mV (n = 5 cells). Under voltage-clamp conditions, the subthreshold potentials of active DRG cells were replaced by fluctuations in outward current. The power spectral density, S(f) of these current fluctuations was approximated by an equation of the form S(f) = (S(o)/[1 + (f/fc) alpha] where 2 less than or equal to a less than or equal to 3 and the half-power frequency fc = 11.3 +/- 3.1 Hz at 23 degrees C (n = 17 cells). The spontaneous voltage fluctuations of active DRG cells were abolished in Ca2+-free saline, and of the divalent metal cations Sr2+, Mg2+, Ba2+, Co2+ and Mn2+, only Sr2+ could substitute for Ca2+ in the maintenance of this activity. Tetraethylammonium ions (1-10 mM) reversibly blocked the spontaneous potentials, while caffeine (10 mM) increased the frequency of these events. The spontaneous voltage fluctuations were not dependent on the presence of spinal cord neurons in the culture plate, and they were also observed in cultured DRG cells derived from adult mice.

  16. Transient Abnormal Myelopoiesis and AML in Down Syndrome: an Update.

    PubMed

    Bhatnagar, Neha; Nizery, Laure; Tunstall, Oliver; Vyas, Paresh; Roberts, Irene

    2016-10-01

    Children with constitutional trisomy 21 (Down syndrome (DS)) have a unique predisposition to develop myeloid leukaemia of Down syndrome (ML-DS). This disorder is preceded by a transient neonatal preleukaemic syndrome, transient abnormal myelopoiesis (TAM). TAM and ML-DS are caused by co-operation between trisomy 21, which itself perturbs fetal haematopoiesis and acquired mutations in the key haematopoietic transcription factor gene GATA1. These mutations are found in almost one third of DS neonates and are frequently clinically and haematologcially 'silent'. While the majority of cases of TAM undergo spontaneous remission, ∼10 % will progress to ML-DS by acquiring transforming mutations in additional oncogenes. Recent advances in the unique biological, cytogenetic and molecular characteristics of TAM and ML-DS are reviewed here.

  17. Spontaneous and posed facial expression in Parkinson's disease.

    PubMed

    Smith, M C; Smith, M K; Ellgring, H

    1996-09-01

    Spontaneous and posed emotional facial expressions in individuals with Parkinson's disease (PD, n = 12) were compared with those of healthy age-matched controls (n = 12). The intensity and amount of facial expression in PD patients were expected to be reduced for spontaneous but not posed expressions. Emotional stimuli were video clips selected from films, 2-5 min in duration, designed to elicit feelings of happiness, sadness, fear, disgust, or anger. Facial movements were coded using Ekman and Friesen's (1978) Facial Action Coding System (FACS). In addition, participants rated their emotional experience on 9-point Likert scales. The PD group showed significantly less overall facial reactivity than did controls when viewing the films. The predicted Group X Condition (spontaneous vs. posed) interaction effect on smile intensity was found when PD participants with more severe disease were compared with those with milder disease and with controls. In contrast, ratings of emotional experience were similar for both groups. Depression was positively associated with emotion rating but not with measures of facial activity. Spontaneous facial expression appears to be selectively affected in PD, whereas posed expression and emotional experience remain relatively intact.

  18. [X-ray computed tomographic abnormalities in schizophrenia. Trial of relationship with clinical data].

    PubMed

    D'Amato, T; Rochet, T; Dalery, J; Chauchat, J H; Terra, J L; Arteaga, C; Marie-Cardine, M

    1992-01-01

    Computerized tomography (CT-scan) studies in schizophrenia revealed that some patients have neuromorphological abnormalities. The structural changes consist mainly in lateral and third ventricle enlargement, and in cortical atrophy. The present study evaluates these three changes in 42 schizophrenics aged 18 to 50, compared to 24 healthy controls. Diagnosis were established from information gathered by personal interview with the SADS-LA. Clinical sub-types were evaluated according to the DSM III-R criteria. Moreover, detailed symptoms were rated according to the Positive And Negative Syndrome Scale (PANSS). CT scans were recorded in floppy disks and blindly analyzed. Schizophrenics shown significant higher mean size of lateral and third ventricles, and higher mean anterior cortical atrophy than healthy subjects. Significant differences were also found between subtypes, with more marked abnormalities in the disorganized group. The relationship between brain abnormalities and clinical symptoms recorded with the PANSS, were analysed using Pearson correlates. Positive correlations concerned mainly negative symptoms like blunted affect, emotional withdrawal, difficulties in abstract thinking, passive apathetic social withdrawal and lack of spontaneity of conversation. Positive correlations are also observed with some symptoms classified with the PANSS in the General Psychopathology scale such as mannerism and disorientation. Negative correlation concerned most of PANSS positive symptoms.

  19. COMPLEMENT ACTIVATION FRAGMENT Bb IN EARLY PREGNANCY AND SPONTANEOUS PRETERM BIRTH

    PubMed Central

    LYNCH, ANNE M.; GIBBS, RONALD S.; MURPHY, JAMES R.; BYERS, TIM; NEVILLE, MARGARET C.; GICLAS, PATRICIA C.; SALMON, JANE E.; VAN HECKE, TRISHA M; MICHAEL HOLERS, V.

    2008-01-01

    Objective To determine if an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks gestation or SPTB between 34 and 37 weeks gestation (late SPTB). Study Design Prospective study of 784 women enrolled at < 20 weeks gestation. Results Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks gestation and 25 (3.2%) a SPTB between 34 and 37 weeks gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks gestation as compared with women who had levels of Bb in the lower three quartiles (95% CI 1.5 to 14, P = 0.003). There was no association between Bb and late SPTB (RR= 0.8, 95% CI = 0.3 to 2). Conclusions A significant relationship was found between an elevated Bb in early pregnancy and SPTB < 34 weeks gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition. PMID:18928972

  20. Slow spontaneous hemodynamic oscillations during sleep measured with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Virtanen, Jaakko; Näsi, Tiina; Noponen, Tommi; Toppila, Jussi; Salmi, Tapani; Ilmoniemi, Risto J.

    2011-07-01

    Spontaneous cerebral hemodynamic oscillations below 100 mHz reflect the level of cerebral activity, modulate hemodynamic responses to tasks and stimuli, and may aid in detecting various pathologies of the brain. Near-infrared spectroscopy (NIRS) is ideally suited for both measuring spontaneous hemodynamic oscillations and monitoring sleep, but little research has been performed to combine these two applications. We analyzed 30 all-night NIRS-electroencephalography (EEG) sleep recordings to investigate spontaneous hemodynamic activity relative to sleep stages determined by polysomnography. Signal power of hemodynamic oscillations in the low-frequency (LF, 40-150 mHz) and very-low-frequency (VLF, 3-40 mHz) bands decreased in slow-wave sleep (SWS) compared to light sleep (LS) and rapid-eye-movement (REM) sleep. No statistically significant (p < 0.05) differences in oscillation power between LS and REM were observed. However, the period of VLF oscillations around 8 mHz increased in REM sleep in line with earlier studies with other modalities. These results increase our knowledge of the physiology of sleep, complement EEG data, and demonstrate the applicability of NIRS to studying spontaneous hemodynamic fluctuations during sleep.

  1. Associations of lifetime active and passive smoking with spontaneous abortion, stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical data from the Women's Health Initiative.

    PubMed

    Hyland, Andrew; Piazza, Kenneth M; Hovey, Kathleen M; Ockene, Judith K; Andrews, Christopher A; Rivard, Cheryl; Wactawski-Wende, Jean

    2015-07-01

    To examine the associations between tobacco exposure and adverse pregnancy outcomes using quantitative measures of lifetime active smoking and secondhand smoke (SHS) exposure. Historical reproductive data on 80 762 women who participated in the Women's Health Initiative Observational Study were examined with a cross-sectional analysis. We assessed self-reported lifetime active and passive tobacco smoke exposure, self-reported spontaneous abortions, stillbirths and ectopic pregnancies. When compared with never-smoking women, participants who were ever active smokers during their reproductive years had ORs (OR) of 1.16 (95% CI 1.08 to 1.26) for 1 or more spontaneous abortions, 1.44 (95% CI 1.20 to 1.73) for 1 or more stillbirths, and 1.43 (95% CI 1.10 to 1.86) for 1 or more ectopic pregnancies. Never-smoking women participants with the highest levels of lifetime SHS exposure, including childhood >10 years, adult home >20 years and adult work exposure >10 years, when compared with never-smoking women with no SHS exposure had adjusted ORs of 1.17 (95% CI 1.05 to 1.30) for spontaneous abortion, 1.55 (95% CI 1.21 to 1.97) for stillbirth, and 1.61 (95% CI 1.16 to 2.24) for ectopic pregnancy. Women who were ever-smokers during their reproductive years had significantly greater estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Never-smoking women with the highest levels of lifetime exposure to SHS had significantly increased estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Spontaneous ad hoc mobile cloud computing network.

    PubMed

    Lacuesta, Raquel; Lloret, Jaime; Sendra, Sandra; Peñalver, Lourdes

    2014-01-01

    Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes.

  3. Enhancement by citral of glutamatergic spontaneous excitatory transmission in adult rat substantia gelatinosa neurons.

    PubMed

    Zhu, Lan; Fujita, Tsugumi; Jiang, Chang-Yu; Kumamoto, Eiichi

    2016-02-10

    Although citral, which is abundantly present in lemongrass, has various actions including antinociception, how citral affects synaptic transmission has not been examined as yet. Citral activates in heterologous cells transient receptor potential vanilloid-1, ankyrin-1, and melastatin-8 (TRPV1, TRPA1, and TRPM8, respectively) channels, the activation of which in the spinal lamina II [substantia gelatinosa (SG)] increases the spontaneous release of L-glutamate from nerve terminals. It remains to be examined what types of transient receptor potential channel in native neurons are activated by citral. With a focus on transient receptor potential activation, we examined the effect of citral on glutamatergic spontaneous excitatory transmission using the whole-cell patch-clamp technique to SG neurons in adult rat spinal cord slices. Bath-applied citral for 3 min increased the frequency of spontaneous excitatory postsynaptic current in a concentration-dependent manner (half-maximal effective concentration=0.58 mM), with a small increase in its amplitude. The spontaneous excitatory postsynaptic current frequency increase produced by citral was repeated at a time interval of 30 min, albeit this action recovered with a slow time course after washout. The presynaptic effect of citral was inhibited by TRPA1 antagonist HC-030031, but not by voltage-gated Na-channel blocker tetrodotoxin, TRPV1 antagonist capsazepine, and TRPM8 antagonist BCTC. It is concluded that citral increases spontaneous L-glutamate release in SG neurons by activating TRPA1 channels. Considering that the SG plays a pivotal role in modulating nociceptive transmission from the periphery, the citral activity could contribute toward at least a part of the modulation.

  4. Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation

    PubMed Central

    Limb, Charles J.; Braun, Allen R.

    2008-01-01

    To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity. PMID:18301756

  5. EGF-dependent re-routing of vesicular recycling switches spontaneous phosphorylation suppression to EGFR signaling

    PubMed Central

    Baumdick, Martin; Brüggemann, Yannick; Schmick, Malte; Xouri, Georgia; Sabet, Ola; Davis, Lloyd; Chin, Jason W; Bastiaens, Philippe IH

    2015-01-01

    Autocatalytic activation of epidermal growth factor receptor (EGFR) coupled to dephosphorylating activity of protein tyrosine phosphatases (PTPs) ensures robust yet diverse responses to extracellular stimuli. The inevitable tradeoff of this plasticity is spontaneous receptor activation and spurious signaling. We show that a ligand-mediated switch in EGFR trafficking enables suppression of spontaneous activation while maintaining EGFR’s capacity to transduce extracellular signals. Autocatalytic phosphorylation of tyrosine 845 on unliganded EGFR monomers is suppressed by vesicular recycling through perinuclear areas with high PTP1B activity. Ligand-binding results in phosphorylation of the c-Cbl docking tyrosine and ubiquitination of the receptor. This secondary signal relies on EGF-induced EGFR self-association and switches suppressive recycling to directional trafficking. The re-routing regulates EGFR signaling response by the transit-time to late endosomes where it is switched-off by high PTP1B activity. This ubiquitin-mediated switch in EGFR trafficking is a uniquely suited solution to suppress spontaneous activation while maintaining responsiveness to EGF. DOI: http://dx.doi.org/10.7554/eLife.12223.001 PMID:26609808

  6. Abnormal Uterine Bleeding

    MedlinePlus

    ... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

  7. Endogenous cholinergic tone modulates spontaneous network level neuronal activity in primary cortical cultures grown on multi-electrode arrays.

    PubMed

    Hammond, Mark W; Xydas, Dimitris; Downes, Julia H; Bucci, Giovanna; Becerra, Victor; Warwick, Kevin; Constanti, Andrew; Nasuto, Slawomir J; Whalley, Benjamin J

    2013-03-26

    Cortical cultures grown long-term on multi-electrode arrays (MEAs) are frequently and extensively used as models of cortical networks in studies of neuronal firing activity, neuropharmacology, toxicology and mechanisms underlying synaptic plasticity. However, in contrast to the predominantly asynchronous neuronal firing activity exhibited by intact cortex, electrophysiological activity of mature cortical cultures is dominated by spontaneous epileptiform-like global burst events which hinders their effective use in network-level studies, particularly for neurally-controlled animat ('artificial animal') applications. Thus, the identification of culture features that can be exploited to produce neuronal activity more representative of that seen in vivo could increase the utility and relevance of studies that employ these preparations. Acetylcholine has a recognised neuromodulatory role affecting excitability, rhythmicity, plasticity and information flow in vivo although its endogenous production by cortical cultures and subsequent functional influence upon neuronal excitability remains unknown. Consequently, using MEA electrophysiological recording supported by immunohistochemical and RT-qPCR methods, we demonstrate for the first time, the presence of intrinsic cholinergic neurons and significant, endogenous cholinergic tone in cortical cultures with a characterisation of the muscarinic and nicotinic components that underlie modulation of spontaneous neuronal activity. We found that tonic muscarinic ACh receptor (mAChR) activation affects global excitability and burst event regularity in a culture age-dependent manner whilst, in contrast, tonic nicotinic ACh receptor (nAChR) activation can modulate burst duration and the proportion of spikes occurring within bursts in a spatio-temporal fashion. We suggest that the presence of significant endogenous cholinergic tone in cortical cultures and the comparability of its modulatory effects to those seen in intact brain

  8. PFOS induces behavioral alterations, including spontaneous hyperactivity that is corrected by dexamfetamine in zebrafish larvae.

    PubMed

    Spulber, Stefan; Kilian, Pascal; Wan Ibrahim, Wan Norhamidah; Onishchenko, Natalia; Ulhaq, Mazhar; Norrgren, Leif; Negri, Sara; Di Tuccio, Marcello; Ceccatelli, Sandra

    2014-01-01

    Perfluorooctane sulfonate (PFOS) is a widely spread environmental contaminant. It accumulates in the brain and has potential neurotoxic effects. The exposure to PFOS has been associated with higher impulsivity and increased ADHD prevalence. We investigated the effects of developmental exposure to PFOS in zebrafish larvae, focusing on the modulation of activity by the dopaminergic system. We exposed zebrafish embryos to 0.1 or 1 mg/L PFOS (0.186 or 1.858 µM, respectively) and assessed swimming activity at 6 dpf. We analyzed the structure of spontaneous activity, the hyperactivity and the habituation during a brief dark period (visual motor response), and the vibrational startle response. The findings in zebrafish larvae were compared with historical data from 3 months old male mice exposed to 0.3 or 3 mg/kg/day PFOS throughout gestation. Finally, we investigated the effects of dexamfetamine on the alterations in spontaneous activity and startle response in zebrafish larvae. We found that zebrafish larvae exposed to 0.1 mg/L PFOS habituate faster than controls during a dark pulse, while the larvae exposed to 1 mg/L PFOS display a disorganized pattern of spontaneous activity and persistent hyperactivity. Similarly, mice exposed to 0.3 mg/kg/day PFOS habituated faster than controls to a new environment, while mice exposed to 3 mg/kg/day PFOS displayed more intense and disorganized spontaneous activity. Dexamfetamine partly corrected the hyperactive phenotype in zebrafish larvae. In conclusion, developmental exposure to PFOS in zebrafish induces spontaneous hyperactivity mediated by a dopaminergic deficit, which can be partially reversed by dexamfetamine in zebrafish larvae.

  9. Analysis of SOS-Induced Spontaneous Prophage Induction in Corynebacterium glutamicum at the Single-Cell Level

    PubMed Central

    Nanda, Arun M.; Heyer, Antonia; Krämer, Christina; Grünberger, Alexander; Kohlheyer, Dietrich

    2014-01-01

    The genome of the Gram-positive soil bacterium Corynebacterium glutamicum ATCC 13032 contains three integrated prophage elements (CGP1 to -3). Recently, it was shown that the large lysogenic prophage CGP3 (∼187 kbp) is excised spontaneously in a small number of cells. In this study, we provide evidence that a spontaneously induced SOS response is partly responsible for the observed spontaneous CGP3 induction. Whereas previous studies focused mainly on the induction of prophages at the population level, we analyzed the spontaneous CGP3 induction at the single-cell level using promoters of phage genes (Pint2 and Plysin) fused to reporter genes encoding fluorescent proteins. Flow-cytometric analysis revealed a spontaneous CGP3 activity in about 0.01 to 0.08% of the cells grown in standard minimal medium, which displayed a significantly reduced viability. A PrecA-eyfp promoter fusion revealed that a small fraction of C. glutamicum cells (∼0.2%) exhibited a spontaneous induction of the SOS response. Correlation of PrecA to the activity of downstream SOS genes (PdivS and PrecN) confirmed a bona fide induction of this stress response rather than stochastic gene expression. Interestingly, the reporter output of PrecA and CGP3 promoter fusions displayed a positive correlation at the single-cell level (ρ = 0.44 to 0.77). Furthermore, analysis of the PrecA-eyfp/Pint2-e2-crimson strain during growth revealed the highest percentage of spontaneous PrecA and Pint2 activity in the early exponential phase, when fast replication occurs. Based on these studies, we postulate that spontaneously occurring DNA damage induces the SOS response, which in turn triggers the induction of lysogenic prophages. PMID:24163339

  10. Central command: control of cardiac sympathetic and vagal efferent nerve activity and the arterial baroreflex during spontaneous motor behaviour in animals.

    PubMed

    Matsukawa, Kanji

    2012-01-01

    Feedforward control by higher brain centres (termed central command) plays a role in the autonomic regulation of the cardiovascular system during exercise. Over the past 20 years, workers in our laboratory have used the precollicular-premammillary decerebrate animal model to identify the neural circuitry involved in the CNS control of cardiac autonomic outflow and arterial baroreflex function. Contrary to the traditional idea that vagal withdrawal at the onset of exercise causes the increase in heart rate, central command did not decrease cardiac vagal efferent nerve activity but did allow cardiac sympathetic efferent nerve activity to produce cardiac acceleration. In addition, central command-evoked inhibition of the aortic baroreceptor-heart rate reflex blunted the baroreflex-mediated bradycardia elicited by aortic nerve stimulation, further increasing the heart rate at the onset of exercise. Spontaneous motor activity and associated cardiovascular responses disappeared in animals decerebrated at the midcollicular level. These findings indicate that the brain region including the caudal diencephalon and extending to the rostral mesencephalon may play a role in generating central command. Bicuculline microinjected into the midbrain ventral tegmental area of decerebrate rats produced a long-lasting repetitive activation of renal sympathetic nerve activity that was synchronized with the motor nerve discharge. When lidocaine was microinjected into the ventral tegmental area, the spontaneous motor activity and associated cardiovascular responses ceased. From these findings, we conclude that cerebral cortical outputs trigger activation of neural circuits within the caudal brain, including the ventral tegmental area, which causes central command to augment cardiac sympathetic outflow at the onset of exercise in decerebrate animal models.

  11. The quality of preterm infants' spontaneous movements: an early indicator of intelligence and behaviour at school age.

    PubMed

    Butcher, Phillipa R; van Braeckel, Koen; Bouma, Anke; Einspieler, Christa; Stremmelaar, Elisabeth F; Bos, Arend F

    2009-08-01

    The quality of very preterm infants' spontaneous movements at 11 to 16 weeks post-term age is a powerful predictor of their later neurological status. This study investigated whether early spontaneous movements also have predictive value for the intellectual and behavioural problems that children born very preterm often experience. Spontaneous movement quality was assessed, using Prechtl's method, at 11 to 16 weeks post-term in 65 infants born at Spontaneous movement quality at 11 to 16 weeks post-term was significantly, positively associated with later intelligence. The number of normal postural patterns displayed contributed most strongly to the association, which was not mediated by neurological status. Fidgety movements, strong predictors of later neurological dysfunction, were not associated with intelligence. Spontaneous movement quality was not associated with internalising or externalising problems but showed a trend to an association with attention problems. These findings suggest that, in children born preterm, early spontaneous movement quality has clear prognostic value for neurological and intellectual outcome, and to a lesser extent, for attentional outcome. However, cognitive outcome was associated with the presence of specific, age-appropriate postural patterns, while neurological outcome has been associated with the presence of global movement abnormalities. The presence of specific, age-appropriate postural patterns may reflect the integrity of areas of the brain involved in cognitive processing and the

  12. Abnormal auditory pattern perception in schizophrenia.

    PubMed

    Haigh, Sarah M; Coffman, Brian A; Murphy, Timothy K; Butera, Christiana D; Salisbury, Dean F

    2016-10-01

    Mismatch negativity (MMN) in response to deviation from physical sound parameters (e.g., pitch, duration) is reduced in individuals with long-term schizophrenia (Sz), suggesting deficits in deviance detection. However, MMN can appear at several time intervals as part of deviance detection. Understanding which part of the processing stream is abnormal in Sz is crucial for understanding MMN pathophysiology. We measured MMN to complex pattern deviants, which have been shown to produce multiple MMNs in healthy controls (HC). Both simple and complex MMNs were recorded from 27 Sz and 27 matched HC. For simple MMN, pitch- and duration-deviants were presented among frequent standard tones. For complex MMN, patterns of five single tones were repeatedly presented, with the occasional deviant group of tones containing an extra sixth tone. Sz showed smaller pitch MMN (p=0.009, ~110ms) and duration MMN (p=0.030, ~170ms) than healthy controls. For complex MMN, there were two deviance-related negativities. The first (~150ms) was not significantly different between HC and SZ. The second was significantly reduced in Sz (p=0.011, ~400ms). The topography of the late complex MMN was consistent with generators in anterior temporal cortex. Worse late MMN in Sz was associated with increased emotional withdrawal, poor attention, lack of spontaneity/conversation, and increased preoccupation. Late MMN blunting in schizophrenia suggests a deficit in later stages of deviance processing. Correlations with negative symptoms measures are preliminary, but suggest that abnormal complex auditory perceptual processes may compound higher-order cognitive and social deficits in the disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Analysis of spontaneous EEG activity in Alzheimer's disease using cross-sample entropy and graph theory.

    PubMed

    Gomez, Carlos; Poza, Jesus; Gomez-Pilar, Javier; Bachiller, Alejandro; Juan-Cruz, Celia; Tola-Arribas, Miguel A; Carreres, Alicia; Cano, Monica; Hornero, Roberto

    2016-08-01

    The aim of this pilot study was to analyze spontaneous electroencephalography (EEG) activity in Alzheimer's disease (AD) by means of Cross-Sample Entropy (Cross-SampEn) and two local measures derived from graph theory: clustering coefficient (CC) and characteristic path length (PL). Five minutes of EEG activity were recorded from 37 patients with dementia due to AD and 29 elderly controls. Our results showed that Cross-SampEn values were lower in the AD group than in the control one for all the interactions among EEG channels. This finding indicates that EEG activity in AD is characterized by a lower statistical dissimilarity among channels. Significant differences were found mainly for fronto-central interactions (p <; 0.01, permutation test). Additionally, the application of graph theory measures revealed diverse neural network changes, i.e. lower CC and higher PL values in AD group, leading to a less efficient brain organization. This study suggests the usefulness of our approach to provide further insights into the underlying brain dynamics associated with AD.

  14. The perception of musical spontaneity in improvised and imitated jazz performances.

    PubMed

    Engel, Annerose; Keller, Peter E

    2011-01-01

    The ability to evaluate spontaneity in human behavior is called upon in the esthetic appreciation of dramatic arts and music. The current study addresses the behavioral and brain mechanisms that mediate the perception of spontaneity in music performance. In a functional magnetic resonance imaging experiment, 22 jazz musicians listened to piano melodies and judged whether they were improvised or imitated. Judgment accuracy (mean 55%; range 44-65%), which was low but above chance, was positively correlated with musical experience and empathy. Analysis of listeners' hemodynamic responses revealed that amygdala activation was stronger for improvisations than imitations. This activation correlated with the variability of performance timing and intensity (loudness) in the melodies, suggesting that the amygdala is involved in the detection of behavioral uncertainty. An analysis based on the subjective classification of melodies according to listeners' judgments revealed that a network including the pre-supplementary motor area, frontal operculum, and anterior insula was most strongly activated for melodies judged to be improvised. This may reflect the increased engagement of an action simulation network when melodic predictions are rendered challenging due to perceived instability in the performer's actions. Taken together, our results suggest that, while certain brain regions in skilled individuals may be generally sensitive to objective cues to spontaneity in human behavior, the ability to evaluate spontaneity accurately depends upon whether an individual's action-related experience and perspective taking skills enable faithful internal simulation of the given behavior.

  15. The Perception of Musical Spontaneity in Improvised and Imitated Jazz Performances

    PubMed Central

    Engel, Annerose; Keller, Peter E.

    2011-01-01

    The ability to evaluate spontaneity in human behavior is called upon in the esthetic appreciation of dramatic arts and music. The current study addresses the behavioral and brain mechanisms that mediate the perception of spontaneity in music performance. In a functional magnetic resonance imaging experiment, 22 jazz musicians listened to piano melodies and judged whether they were improvised or imitated. Judgment accuracy (mean 55%; range 44–65%), which was low but above chance, was positively correlated with musical experience and empathy. Analysis of listeners’ hemodynamic responses revealed that amygdala activation was stronger for improvisations than imitations. This activation correlated with the variability of performance timing and intensity (loudness) in the melodies, suggesting that the amygdala is involved in the detection of behavioral uncertainty. An analysis based on the subjective classification of melodies according to listeners’ judgments revealed that a network including the pre-supplementary motor area, frontal operculum, and anterior insula was most strongly activated for melodies judged to be improvised. This may reflect the increased engagement of an action simulation network when melodic predictions are rendered challenging due to perceived instability in the performer's actions. Taken together, our results suggest that, while certain brain regions in skilled individuals may be generally sensitive to objective cues to spontaneity in human behavior, the ability to evaluate spontaneity accurately depends upon whether an individual's action-related experience and perspective taking skills enable faithful internal simulation of the given behavior. PMID:21738518

  16. Imbalanced spontaneous brain activity in orbitofrontal-insular circuits in individuals with cognitive vulnerability to depression.

    PubMed

    Zhang, Xiaocui; Di, Xin; Lei, Hui; Yang, Juan; Xiao, Jing; Wang, Xiang; Yao, Shuqiao; Rao, Hengyi

    2016-07-01

    The hopelessness theory of depression posits that individuals with negative cognitive styles are at risk of developing depression following negative life events. The purpose of this work was to examine whether individuals with cognitive vulnerability to depression (CVD) exhibit similar spontaneous brain activity patterns as compared to patients with major depressive disorder (MDD). Subjects with CVD (N=32), drug-naïve first-episode patients with major depressive disorder (N=32), and sex-, age- and education-matched healthy controls (HCs; N=35) were subjected to resting state functional magnetic resonance imaging (RS-fMRI) and amplitudes of low-frequency fluctuation (ALFF) was compared between the groups. Pearson correlation analysis was performed between regional ALFFs and psychometric scores, namely the Cognitive Style Questionnaire (CSQ) and the Center for Epidemiologic Studies Depression (CES-D) scale scores. Significant group differences in ALFF values were observed bilaterally in the orbitofrontal cortex (OFC) and insular cortex (IC), and in the left fusiform gyrus (FFG). Compared to HCs, CVD subjects had reduced ALFFs in the bilateral OFC and increased ALFF in the bilateral IC and the left FFG, which were similar to the differences observed between the HCs and MDD patients. Compared to MDD patients, CVD subjects showed significant reduced ALFF values in right IC. Additionally, CSQ scores for the CVD group correlated with ALFF values in the left IC. We did not conduct a longitudinal study. Our findings were limited in cross-sectional analysis. A hypoactive OFC and hyperactive IC in a resting-state may underlie an imbalance in the spontaneous brain activity in orbitofrontal-insular circuits, and these differences may represent a trait-related marker of vulnerability to depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Arteriolymphatic Fistula: An Unusual Cause of Spontaneous Swelling in the Left Supraclavicular Region

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Karuppiah Viswanathan, Ashok Mithra, E-mail: ashokmithrakv@gmail.com; Irodi, Aparna; Keshava, Shyamkumar N., E-mail: aparna-shyam@yahoo.com

    2016-09-15

    An abnormal fistulous communication between an artery and lymphatic system is a rare occurrence. We report a 38-year-old male presenting with sudden onset, spontaneous, pulsatile swelling in the left supraclavicular region following a recent cardiac catheterisation via right femoral arterial access. On evaluation, he was found to have a femoral arteriolymphatic fistula. He was managed conservatively with ultrasound-guided compression with complete resolution of symptoms at follow-up. This case describes a hitherto unknown complication of percutaneous vascular cannulation presenting in an unusual manner, diagnosed with Doppler Ultrasonography and CT angiography and managed effectively with a non-invasive therapeutic image-guided manoeuvre.

  18. BRAIN ACONITASE ACTIVITY IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR-KYOTO (WKY) RATS.

    EPA Science Inventory

    Animal models of susceptibility are critical for human health risk assessment. Previous studies indicate that spontaneously hypertensive (SHR) rats are more sensitive than Wistar-Kyoto (WKY) rats to the cholinesterase (ChE) inhibitors such as carbaryl and chlorpyrifos. This diffe...

  19. [Spontaneous bacterial peritonitis].

    PubMed

    Velkey, Bálint; Vitális, Eszter; Vitális, Zsuzsanna

    2017-01-01

    Spontaneous bacterial peritonitis occurs most commonly in cirrhotic patients with ascites. Pathogens get into the circulation by intestinal translocation and colonize in peritoneal fluid. Diagnosis of spontaneous bacterial peritonitis is based on elevated polymorphonuclear leukocyte count in the ascites (>0,25 G/L). Ascites culture is often negative but aids to get information about antibiotic sensitivity in positive cases. Treatment in stable patient can be intravenous then orally administrated ciprofloxacin or amoxicillin/clavulanic acid, while in severe cases intravenous III. generation cephalosporin. Nosocomial spontaneous bacterial peritonitis often caused by Gram-positive bacteria and multi-resistant pathogens can also be expected thus carbapenem should be the choice of the empiric treatment. Antibiotic prophylaxis should be considered. Norfloxacin is used most commonly, but changes are expected due to increase in quinolone resistance. As a primary prophylaxis, a short-term antibiotic treatment is recommended after gastrointestinal bleeding for 5 days, while long-term prophylaxis is for patients with low ascites protein, and advanced disease (400 mg/day). Secondary prophylaxis is recommended for all patients recovered from spontaneous bacterial peritonitis. Due to increasing antibiotic use of antibiotics prophylaxis is debated to some degree. Orv. Hetil., 2017, 158(2), 50-57.

  20. High-efficiency electroluminescence and amplified spontaneous emission from a thermally activated delayed fluorescent near-infrared emitter

    NASA Astrophysics Data System (ADS)

    Kim, Dae-Hyeon; D'Aléo, Anthony; Chen, Xian-Kai; Sandanayaka, Atula D. S.; Yao, Dandan; Zhao, Li; Komino, Takeshi; Zaborova, Elena; Canard, Gabriel; Tsuchiya, Youichi; Choi, Eunyoung; Wu, Jeong Weon; Fages, Frédéric; Brédas, Jean-Luc; Ribierre, Jean-Charles; Adachi, Chihaya

    2018-02-01

    Near-infrared organic light-emitting diodes and semiconductor lasers could benefit a variety of applications including night-vision displays, sensors and information-secured displays. Organic dyes can generate electroluminescence efficiently at visible wavelengths, but organic light-emitting diodes are still underperforming in the near-infrared region. Here, we report thermally activated delayed fluorescent organic light-emitting diodes that operate at near-infrared wavelengths with a maximum external quantum efficiency of nearly 10% using a boron difluoride curcuminoid derivative. As well as an effective upconversion from triplet to singlet excited states due to the non-adiabatic coupling effect, this donor-acceptor-donor compound also exhibits efficient amplified spontaneous emission. By controlling the polarity of the active medium, the maximum emission wavelength of the electroluminescence spectrum can be tuned from 700 to 780 nm. This study represents an important advance in near-infrared organic light-emitting diodes and the design of alternative molecular architectures for photonic applications based on thermally activated delayed fluorescence.

  1. Resting-state activity in development and maintenance of normal brain function.

    PubMed

    Pizoli, Carolyn E; Shah, Manish N; Snyder, Abraham Z; Shimony, Joshua S; Limbrick, David D; Raichle, Marcus E; Schlaggar, Bradley L; Smyth, Matthew D

    2011-07-12

    One of the most intriguing recent discoveries concerning brain function is that intrinsic neuronal activity manifests as spontaneous fluctuations of the blood oxygen level-dependent (BOLD) functional MRI signal. These BOLD fluctuations exhibit temporal synchrony within widely distributed brain regions known as resting-state networks. Resting-state networks are present in the waking state, during sleep, and under general anesthesia, suggesting that spontaneous neuronal activity plays a fundamental role in brain function. Despite its ubiquitous presence, the physiological role of correlated, spontaneous neuronal activity remains poorly understood. One hypothesis is that this activity is critical for the development of synaptic connections and maintenance of synaptic homeostasis. We had a unique opportunity to test this hypothesis in a 5-y-old boy with severe epileptic encephalopathy. The child developed marked neurologic dysfunction in association with a seizure disorder, resulting in a 1-y period of behavioral regression and progressive loss of developmental milestones. His EEG showed a markedly abnormal pattern of high-amplitude, disorganized slow activity with frequent generalized and multifocal epileptiform discharges. Resting-state functional connectivity MRI showed reduced BOLD fluctuations and a pervasive lack of normal connectivity. The child underwent successful corpus callosotomy surgery for treatment of drop seizures. Postoperatively, the patient's behavior returned to baseline, and he resumed development of new skills. The waking EEG revealed a normal background, and functional connectivity MRI demonstrated restoration of functional connectivity architecture. These results provide evidence that intrinsic, coherent neuronal signaling may be essential to the development and maintenance of the brain's functional organization.

  2. Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection

    PubMed Central

    Sciaranghella, Gaia; Tong, Neath; Mahan, Alison E.; Suscovich, Todd J.; Alter, Galit

    2013-01-01

    Objective To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection. Design Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction. Methods Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication. Results Although the emergence of exhausted, CD21low tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21low activated memory B cells was lower in spontaneous controllers. Conclusion Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment. PMID:23135171

  3. Acute dynamin inhibition dissects synaptic vesicle recycling pathways that drive spontaneous and evoked neurotransmission

    PubMed Central

    Chung, ChiHye; Barlyko, Barbara; Leitz, Jeremy; Liu, Xinran; Kavalali, Ege T.

    2010-01-01

    Synapses maintain synchronous, asynchronous and spontaneous forms of neurotransmission that are distinguished by their Ca2+-dependence and time course. Despite recent advances in our understanding of the mechanisms that underlie these three forms of release, it remains unclear whether they originate from the same vesicle population or arise from distinct vesicle pools with diverse propensities for release. Here, we used a reversible inhibitor of dynamin, dynasore, to dissect the vesicle pool dynamics underlying the three forms of neurotransmitter release in hippocampal GABAergic inhibitory synapses. In dynasore, evoked synchronous release and asynchronous neurotransmission detected after activity showed marked and unrecoverable depression within seconds. In contrast, spontaneous release remained intact after intense stimulation in dynasore or during prolonged (~1 hour) application of dynasore at rest, suggesting that separate recycling pathways maintain evoked and spontaneous synaptic vesicle trafficking. In addition, simultaneous imaging of spectrally separable styryl dyes revealed that in a given synapse vesicles that recycle spontaneously and in response to activity do not mix. These findings suggest that evoked synchronous and asynchronous release originate from the same vesicle pool that recycles rapidly in a dynamin-dependent manner, while a distinct vesicle pool sustains spontaneous release independent of dynamin activation. This result lends further support to the notion that synapses harbor distinct vesicle populations with divergent release properties that maintain independent forms of neurotransmission. PMID:20107062

  4. Spontaneous mirror-symmetry breaking induces inverse energy cascade in 3D active fluids

    PubMed Central

    Słomka, Jonasz; Dunkel, Jörn

    2017-01-01

    Classical turbulence theory assumes that energy transport in a 3D turbulent flow proceeds through a Richardson cascade whereby larger vortices successively decay into smaller ones. By contrast, an additional inverse cascade characterized by vortex growth exists in 2D fluids and gases, with profound implications for meteorological flows and fluid mixing. The possibility of a helicity-driven inverse cascade in 3D fluids had been rejected in the 1970s based on equilibrium-thermodynamic arguments. Recently, however, it was proposed that certain symmetry-breaking processes could potentially trigger a 3D inverse cascade, but no physical system exhibiting this phenomenon has been identified to date. Here, we present analytical and numerical evidence for the existence of an inverse energy cascade in an experimentally validated 3D active fluid model, describing microbial suspension flows that spontaneously break mirror symmetry. We show analytically that self-organized scale selection, a generic feature of many biological and engineered nonequilibrium fluids, can generate parity-violating Beltrami flows. Our simulations further demonstrate how active scale selection controls mirror-symmetry breaking and the emergence of a 3D inverse cascade. PMID:28193853

  5. Correlation between protein expression of FOXP3 and level of FOXP3 promoter methylation in recurrent spontaneous abortion.

    PubMed

    Hou, Wenhui; Li, Zhuyu; Li, Yinguang; Fang, Liyuan; Li, Jie; Huang, Jia; Li, Xiaoqing; You, Zeshan

    2016-11-01

    The aim of this study was to investigate the level of Forkhead box P3 (FOXP3) promoter methylation and protein expression in recurrent spontaneous abortion and to elucidate the pathogenesis of unexplained recurrent spontaneous abortion (URSA). We assessed a total of 56 URSA patients with a normal embryo, 24 recurrent spontaneous abortion (RSA) patients with an abnormal embryo (as control group 1), and 39 normal pregnant women (as control group 2). The expression of FOXP3 protein in deciduas was assessed through Western blot, and the level of FOXP3 promoter methylation was detected using bisulfite-assisted genomic sequencing polymerase chain reaction. The expressing quantity of FOXP3 protein in the URSA group was significantly lower than that in control groups 1 and 2, both with a P-value < 0.05. By contrast, no statistical difference was observed in the expressing quantity of FOXP3 protein of the two control groups (P = 0.212). The FOXP3 promoter methylation level in the URSA group was significantly higher than that in the two control groups, both of which exhibited a statistical difference of P-values < 0.05. Meanwhile, no statistical difference was observed in the FOXP3 promoter methylation level of the two control groups (P = 0.141). A negative correlation was found between the FOXP3 promoter methylation level and the expressing quantity of FOXP3 protein (r = -0.861, P < 0.05). Increasing FOXP3 promoter methylation levels may cause abnormal immune tolerance through the downregulation expression of the FOXP3 protein, which in turn leads to URSA. © 2016 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.

  6. Accurate means of detecting and characterizing abnormal patterns of ventricular activation by phase image analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Botvinick, E.H.; Frais, M.A.; Shosa, D.W.

    1982-08-01

    The ability of scintigraphic phase image analysis to characterize patterns of abnormal ventricular activation was investigated. The pattern of phase distribution and sequential phase changes over both right and left ventricular regions of interest were evaluated in 16 patients with normal electrical activation and wall motion and compared with those in 8 patients with an artificial pacemaker and 4 patients with sinus rhythm with the Wolff-Parkinson-White syndrome and delta waves. Normally, the site of earliest phase angle was seen at the base of the interventricular septum, with sequential change affecting the body of the septum and the cardiac apex andmore » then spreading laterally to involve the body of both ventricles. The site of earliest phase angle was located at the apex of the right ventricle in seven patients with a right ventricular endocardial pacemaker and on the lateral left ventricular wall in one patient with a left ventricular epicardial pacemaker. In each case the site corresponded exactly to the position of the pacing electrode as seen on posteroanterior and left lateral chest X-ray films, and sequential phase changes spread from the initial focus to affect both ventricles. In each of the patients with the Wolff-Parkinson-White syndrome, the site of earliest ventricular phase angle was located, and it corresponded exactly to the site of the bypass tract as determined by endocardial mapping. In this way, four bypass pathways, two posterior left paraseptal, one left lateral and one right lateral, were correctly localized scintigraphically. On the basis of the sequence of mechanical contraction, phase image analysis provides an accurate noninvasive method of detecting abnormal foci of ventricular activation.« less

  7. Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family.

    PubMed

    Hasanzadeh-NazarAbadi, Mohammad; Baghbani, Fatemeh; Namazi, Iman; Mirzaee, Salmeh

    2014-08-01

    Approximately 205 million pregnancies occur each year in the worldwide. On the other hand, Spontaneous abortion has been reported in 15-20% of all diagnosed pregnancies. The most common cause of spontaneous abortion is chromosomal abnormalities of the embryo. Robertsonian translocation carriers specially 21-14 are the most common balanced rearrangement among the carrier couples with the history of spontaneous abortion. In order to search for balanced chromosomal rearrangement and cytogenetic disorders, 10 members of related family with consanguinity marriage with the history of recurrent miscarriage were assessed. Cytogenetic evaluation on the basis G-banding technique at high resolution was performed in 3 couples and their related family with the history of idiopathic RSA in order to postulate any balanced chromosomal rearrangement. six members of them appeared with robertsonian balanced translocation between chromosome No.21 to No. 14 with the karyotype of 45, XX, t (14, 21) and 45, XY, t (14, 21), which this results are in agreement with several similar works which claimed that the risk of spontaneous abortion in couples with balanced chromosomal rearrangements is higher compared with general population. Considering to results of present study, it seems as if the cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer wills valuable information for genetic consulting.

  8. Gamma abnormalities during perception of illusory figures in autism.

    PubMed

    Brown, Caroline; Gruber, Thomas; Boucher, Jill; Rippon, Gina; Brock, Jon

    2005-06-01

    This experiment was designed to test the hypothesis that perceptual abnormalities in autism might be associated with alteration of induced gamma activity patterns overlying visual cortical regions. EEG was recorded from six adolescents with autism and eight controls matched on chronological age, and verbal and nonverbal mental age, whilst identifying the presence or absence of an illusory Kanizsa shape. Although there were no reaction time or accuracy differences between the groups there were significant task-related differences in cortical activity. Control participants showed typical gamma-band activity over parietal regions at around 350 msec post onset of shape trials, similar to gamma patterns found in previous studies with non-impaired adults. In contrast, autistic participants showed overall increased activity, including an early 100 msec gamma peak and a late induced peak, 50 to 70 msec earlier than that shown by the control group. We interpret the abnormal gamma activity to reflect decreased "signal to noise" due to decreased inhibitory processing. In this experiment we did not establish a link between altered perception and abnormal gamma, as the autistic participants' behaviour did not differ from the controls. Future work should be designed to replicate this phenomenon and establish the perceptual consequences of altered gamma activity.

  9. Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis.

    PubMed

    Alshikho, Mohamad J; Zürcher, Nicole R; Loggia, Marco L; Cernasov, Paul; Chonde, Daniel B; Izquierdo Garcia, David; Yasek, Julia E; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R; Cudkowicz, Merit E; Hooker, Jacob M; Atassi, Nazem

    2016-12-13

    In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [ 11 C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [ 11 C]-PBR28 uptake. In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [ 11 C]-PBR28 binding in the left motor cortex was correlated with FA (r = -0.68, p < 0.05) and cortical thickness (r = -0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = -0.77, p < 0.05), and cortical thickness (r = -0.75, p < 0.05) in the motor cortex. Increased uptake of the glial marker [ 11 C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. © 2016 American Academy of Neurology.

  10. [Primary spontaneous pneumomediastinum].

    PubMed

    Togashi, K; Hosaka, Y

    2007-12-01

    We report 5 cases of spontaneous pneumomediastinum. They were 4 men and 1 female with a mean age of 17 (14-25). Four patients developed sport-related pneumomediastinum and 1 patient had a karaoke-related condition. Primary spontaneous pneumomediasinum is a rare condition. In addition, there is no previous report describing karaoke-related spontaneous pneumomediastinum. Each of the patients experienced chest pain and/or neck pain before consulting our hospital. Chest roentgenogram and chest computed tomography showed pneumomediastinum without esophageal or tracheal injury. Four patients did not require hospitalization, but 1 patient was necessary to hospitalize for 7 days because of severe chest and neck pain. None of these 5 patients has had any recurrence for more than 1 year. Differentiating this entity from other diseases involving anterior chest pain is important.

  11. Spontaneous seizures in a rat model of multiple prenatal freeze lesioning.

    PubMed

    Kamada, Takashi; Sun, Wei; Takase, Kei-Ichiro; Shigeto, Hiroshi; Suzuki, Satoshi O; Ohyagi, Yasumasa; Kira, Jun-Ichi

    2013-08-01

    Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Electroencephalogram (EEG) and video recording were performed from postnatal day (P) 35 to P77. Brain tissues were examined immunohistochemically at P28 and P78 using semiquantitative densitometry. Eleven of 16 rats (68.8%) showed spontaneous seizures arising in the hippocampus from P47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. FCD was observed in the bilateral frontoparietal lobes. The expression levels of N-methyl-d-aspartate receptor (NMDAR) subunits 1, 2A, 2B, the glutamate/aspartate transporter and the glial glutamate transporter 1 (GLT1) at FCD sites were increased at P28 and P78. There were no major histological abnormalities in the hippocampi compared with those in the cortex. However, the expression levels of NMDAR 2A and 2B were increased at P28. Levels of NMDAR1, 2A and 2B, the glutamate/aspartate transporter and GLT1 were also increased at P78. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. Alterations in the levels of glutamatergic and GABAergic

  12. Abnormal kinetic behavior of cytochrome oxidase in a case of Leigh disease.

    PubMed Central

    Glerum, M; Robinson, B H; Spratt, C; Wilson, J; Patrick, D

    1987-01-01

    Cultured skin fibroblasts from a child with fatal lacticacidemia displayed an abnormally high lactate:pyruvate ratio of 77:1, compared with control values of 22:1-27:1. When protease-treated isolated mitochondria were used, activity of the respiratory-chain enzymes was found to be approximately 60% of normal, and adenosine triphosphate synthesis was found to be normal with all substrates tested. In mitochondria prepared by means of digitonin treatment, adenosine triphosphate synthesis was depressed with all substrates tested, suggesting a defect in the operation of the cytochrome oxidase complex. In disrupted whole cells from the patient, cytochrome oxidase activity was 56% of the activity in the control cell line with the lowest activity. In the presence of a twofold excess of oxidized cytochrome c, patient cells showed 31% of the activity in controls. Cytochrome oxidase activity in both sonicated whole-cell preparations and in sonicated mitochondria displayed abnormal kinetics with regard to the substrate-reduced cytochrome c, which was particularly evident in the presence of excess oxidized cytochrome c. We believe that kinetically abnormal cytochrome oxidase complex is responsible for the biochemical and clinical abnormalities present in this patient. PMID:2821802

  13. Lysyl Oxidase Induces Vascular Oxidative Stress and Contributes to Arterial Stiffness and Abnormal Elastin Structure in Hypertension: Role of p38MAPK

    PubMed Central

    Martínez-Revelles, Sonia; García-Redondo, Ana B.; Avendaño, María S.; Varona, Saray; Palao, Teresa; Orriols, Mar; Roque, Fernanda R.; Fortuño, Ana; Touyz, Rhian M.; Martínez-González, Jose; Salaices, Mercedes

    2017-01-01

    Abstract Aims: Vascular stiffness, structural elastin abnormalities, and increased oxidative stress are hallmarks of hypertension. Lysyl oxidase (LOX) is an elastin crosslinking enzyme that produces H2O2 as a by-product. We addressed the interplay between LOX, oxidative stress, vessel stiffness, and elastin. Results: Angiotensin II (Ang II)-infused hypertensive mice and spontaneously hypertensive rats (SHR) showed increased vascular LOX expression and stiffness and an abnormal elastin structure. Mice over-expressing LOX in vascular smooth muscle cells (TgLOX) exhibited similar mechanical and elastin alterations to those of hypertensive models. LOX inhibition with β-aminopropionitrile (BAPN) attenuated mechanical and elastin alterations in TgLOX mice, Ang II-infused mice, and SHR. Arteries from TgLOX mice, Ang II-infused mice, and/or SHR exhibited increased vascular H2O2 and O2.− levels, NADPH oxidase activity, and/or mitochondrial dysfunction. BAPN prevented the higher oxidative stress in hypertensive models. Treatment of TgLOX and Ang II-infused mice and SHR with the mitochondrial-targeted superoxide dismutase mimetic mito-TEMPO, the antioxidant apocynin, or the H2O2 scavenger polyethylene glycol-conjugated catalase (PEG-catalase) reduced oxidative stress, vascular stiffness, and elastin alterations. Vascular p38 mitogen-activated protein kinase (p38MAPK) activation was increased in Ang II-infused and TgLOX mice and this effect was prevented by BAPN, mito-TEMPO, or PEG-catalase. SB203580, the p38MAPK inhibitor, normalized vessel stiffness and elastin structure in TgLOX mice. Innovation: We identify LOX as a novel source of vascular reactive oxygen species and a new pathway involved in vascular stiffness and elastin remodeling in hypertension. Conclusion: LOX up-regulation is associated with enhanced oxidative stress that promotes p38MAPK activation, elastin structural alterations, and vascular stiffness. This pathway contributes to vascular abnormalities in

  14. Spontaneous evaluative inferences and their relationship to spontaneous trait inferences.

    PubMed

    Schneid, Erica D; Carlston, Donal E; Skowronski, John J

    2015-05-01

    Three experiments are reported that explore affectively based spontaneous evaluative impressions (SEIs) of stimulus persons. Experiments 1 and 2 used modified versions of the savings in relearning paradigm (Carlston & Skowronski, 1994) to confirm the occurrence of SEIs, indicating that they are equivalent whether participants are instructed to form trait impressions, evaluative impressions, or neither. These experiments also show that SEIs occur independently of explicit recall for the trait implications of the stimuli. Experiment 3 provides a single dissociation test to distinguish SEIs from spontaneous trait inferences (STIs), showing that disrupting cognitive processing interferes with a trait-based prediction task that presumably reflects STIs, but not with an affectively based social approach task that presumably reflects SEIs. Implications of these findings for the potential independence of spontaneous trait and evaluative inferences, as well as limitations and important steps for future study are discussed. (c) 2015 APA, all rights reserved).

  15. Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

    PubMed

    Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

    2016-07-01

    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.

  16. Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia

    PubMed Central

    Segarra, Nuria; Metastasio, Antonio; Ziauddeen, Hisham; Spencer, Jennifer; Reinders, Niels R; Dudas, Robert B; Arrondo, Gonzalo; Robbins, Trevor W; Clark, Luke; Fletcher, Paul C; Murray, Graham K

    2016-01-01

    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states. PMID:26708106

  17. [Oxytocin administration during spontaneous labour: Guidelines for clinical practice. Guidelines short text].

    PubMed

    Dupont, C; Carayol, M; Le Ray, C; Barasinski, C; Beranger, R; Burguet, A; Chantry, A; Chiesa, C; Coulm, B; Evrard, A; Fischer, C; Gaucher, L; Guillou, C; Leroy, F; Phan, E; Rousseau, A; Tessier, V; Vendittelli, F; Deneux-Tharaux, C; Riethmuller, D

    2017-01-01

    To define the different stages of spontaneous labour. To determine the indications, modalities of use and the effects of administering synthetic oxytocin. And to describe undesirable maternal and perinatal outcomes associated with the use of synthetic oxytocin. A systematic review was carried out by searching Medline database and websites of obstetrics learned societies until March 2016. The 1st stage of labor is divided in a latence phase and an active phase, which switch at 5cm of cervical dilatation. Rate of cervical dilatation is considered as abnormal below 1cm per 4hour during the first part of the active phase, and below 1cm per 2hours above 7cm of dilatation. During the latent phase of the first stage of labor, i.e. before 5cm of cervical dilatation, it is recommended that an amniotomy not be performed routinely and not to use oxytocin systematically. It is not recommended to expect the active phase of labor to start the epidural analgesia if patient requires it. If early epidural analgesia was performed, the administration of oxytocin must not be systematic. If dystocia during the active phase, an amniotomy is recommended in first-line treatment. In the absence of an improvement within an hour, oxytocin should be administrated. However, in the case of an extension of the second stage beyond 2hours, it is recommended to administer oxytocin to correct a lack of progress of the presentation. If dynamic dystocia, it is recommended to start initial doses of oxytocin at 2mUI/min, to respect at least 30min intervals between increases in oxytocin doses delivered, and to increase oxytocin doses by 2mUI/min intervals without surpassing a maximum IV flow rate of 20mUI/min. The reported maternal adverse effects concern uterine hyperstimulation, uterine rupture and post-partum haemorrhage, and those of neonatal adverse effects concern foetal heart rate anomalies associated with uterine hyperstimulation, neonatal morbidity and mortality, neonatal jaundice, weak suck

  18. Non-traumatic and spontaneous hemothorax in the setting of forensic medical examination: a systematic literature survey.

    PubMed

    Janik, Martin; Straka, Lubomir; Krajcovic, Jozef; Hejna, Petr; Hamzik, Julian; Novomesky, Frantisek

    2014-03-01

    Spontaneous hemothorax is a well-known yet seldom-reported entity in forensic literature. While trauma-related hemothorax is frequently encountered in a medicolegal setting, non-traumatic and spontaneous hemothorax are relatively uncommon entities. The wide range of causes that can trigger fatal intrathoracic bleeding include thoracic aortic dissection, followed by vascular malformations, various oncological diseases, and connective tissue abnormalities. In rare instances, extramedullary hematopoiesis, ectopic pregnancy, congenital heart defects, amyloidosis, or parasitic diseases may constitute a source of bleeding. This etiological heterogeneity may, as a result, cause diagnostic difficulties during post-mortem elucidation of hemothorax. It should be borne in mind that hemothorax after low-energy trauma does not exclusively indicate traumatic hemorrhage, hence, the non-traumatic origin of bleeding must be taken into consideration. In this paper, we present a systematic review of the relevant literature enriched by the results of our observations to investigate the etiologies and recommendations for the post-mortem diagnosis of spontaneous hemothorax in an attempt to better delineate the possible medicolegal considerations. It is important that forensic pathologist as well as clinicians are aware of the diseases that could potentially give rise to fatal hemothorax. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  19. [Spontaneous bacterial peritonitis: impact of microbiological changes].

    PubMed

    Almeida, Paulo Roberto Lerias de; Camargo, Nutianne Schneider; Arenz, Maximilhano; Tovo, Cristiane Valle; Galperim, Bruno; Behar, Paulo

    2007-01-01

    Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and the changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used in the treatment. To evaluate the change in the epidemiology and antibiotic resistance of the bacteria causing spontaneous bacterial peritonitis in a 7 years period. All the cases of cirrhotic patients with spontaneous bacterial peritonitis with positive cultural examination were retrospectively studied. Two periods were evaluated: 1997-1998 and 2002-2003. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. In the first period (1997-1998) there were 33 cases, 3 (9%) with polymicrobial infection. The most common were: E.coli in 13 (36,11%), Staphylococcus coagulase-negative in 6 (16,66%), K. pneumoniae in 5 (13,88%), S. aureus in 4 (11,11%) and S. faecalis in 3 (8,33%). In 2003-2004, there were 43 cases, 2 (5%) with polymicrobial infection. The most frequent were: Staphylococus coagulase-negative in 16 (35,55%), S. aureus in 8 (17,77%), E. coli in 7 (15,55%) and K. pneumoniae in 3 (6,66%). No one was using antibiotic prophilaxys. The prevalence of S. aureus methicillin-resitant to quinolone and trimethoprim-sulfamethoxazole changed from 25% to 50%, and vancomicin was the only one with absolute activity during all the period. In the same way, the prevalence of E. coli resistant to third generation cephalosporin and to quinolone changed from 0% to 16%. There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.

  20. Heart rate dynamics before spontaneous onset of ventricular fibrillation in patients with healed myocardial infarcts

    NASA Technical Reports Server (NTRS)

    Makikallio, T. H.; Koistinen, J.; Jordaens, L.; Tulppo, M. P.; Wood, N.; Golosarsky, B.; Peng, C. K.; Goldberger, A. L.; Huikuri, H. V.

    1999-01-01

    The traditional methods of analyzing heart rate (HR) variability have failed to predict imminent ventricular fibrillation (VF). We sought to determine whether new methods of analyzing RR interval variability based on nonlinear dynamics and fractal analysis may help to detect subtle abnormalities in RR interval behavior before the onset of life-threatening arrhythmias. RR interval dynamics were analyzed from 24-hour Holter recordings of 15 patients who experienced VF during electrocardiographic recording. Thirty patients without spontaneous or inducible arrhythmia events served as a control group in this retrospective case control study. Conventional time- and frequency-domain measurements, the short-term fractal scaling exponent (alpha) obtained by detrended fluctuation analysis, and the slope (beta) of the power-law regression line (log power - log frequency, 10(-4)-10(-2) Hz) of RR interval dynamics were determined. The short-term correlation exponent alpha of RR intervals (0.64 +/- 0.19 vs 1.05 +/- 0.12; p <0.001) and the power-law slope beta (-1.63 +/- 0.28 vs -1.31 +/- 0.20, p <0.001) were lower in the patients before the onset of VF than in the control patients, but the SD and the low-frequency spectral components of RR intervals did not differ between the groups. The short-term scaling exponent performed better than any other measurement of HR variability in differentiating between the patients with VF and controls. Altered fractal correlation properties of HR behavior precede the spontaneous onset of VF. Dynamic analysis methods of analyzing RR intervals may help to identify abnormalities in HR behavior before VF.

  1. Complement activation fragment Bb in early pregnancy and spontaneous preterm birth.

    PubMed

    Lynch, Anne M; Gibbs, Ronald S; Murphy, James R; Byers, Tim; Neville, Margaret C; Giclas, Patricia C; Salmon, Jane E; Van Hecke, Trisha M; Holers, V Michael

    2008-10-01

    The objective of this study was to determine whether an elevated level of the complement activation fragment Bb in early pregnancy was associated with spontaneous preterm birth (SPTB) at less than 34 weeks' gestation or SPTB between 34 and 37 weeks' gestation (late SPTB). This was a prospective study of 784 women enrolled at less than 20 weeks' gestation. Following exclusions, 13 women (1.7%) had a SPTB at less than 34 weeks' gestation and 25 (3.2%) a SPTB between 34 and 37 weeks' gestation. Women with Bb in the top quartile were 4.7 times more likely to have an SPTB less than 34 weeks' gestation as compared with women who had levels of Bb in the lower 3 quartiles (95% confidence interval [CI] 1.5-14, P = .003). There was no association between Bb and late SPTB (relative risk 0.8, 95% CI 0.3-2). A significant relationship was found between an elevated Bb in early pregnancy and SPTB less than 34 weeks' gestation. These results suggest that inflammatory events in early pregnancy are part of the pathogenic mechanisms of this condition.

  2. Spontaneous Seizures and Altered Gene Expression in GABA Signaling Pathways in a mind bomb Mutant Zebrafish

    PubMed Central

    Hortopan, Gabriela A.; Dinday, Matthew T.; Baraban, Scott C.

    2010-01-01

    Disruption of E3 ubiquitin ligase activity in immature zebrafish mind bomb mutants, leads to a failure in Notch signaling, excessive numbers of neurons, and depletion of neural progenitor cells. This neurogenic phenotype is associated with defects in neural patterning and brain development. Because developmental brain abnormalities are recognized as an important feature of childhood neurological disorders such as epilepsy and autism, we determined whether zebrafish mutants with grossly abnormal brain structure exhibit spontaneous electrical activity that resembles the long-duration, high-amplitude multi-spike discharges reported in immature zebrafish exposed to convulsant drugs. Electrophysiological recordings from agar immobilized mind bomb mutants at three days postfertilization (dpf) confirmed the occurrence of electrographic seizure activity; seizure-like behaviors were also noted during locomotion video tracking of freely behaving mutants. To identify genes differentially expressed in the mind bomb mutant and provide insight into molecular pathways that may mediate these epileptic phenotypes, a transcriptome analysis was performed using microarray. Interesting candidate genes were further analyzed using conventional reverse transcriptasepolymerase chain reaction (RT-PCR) and real-time quantitative PCR (qPCR), as well as whole-mount in situ hybridization. Approximately 150 genes, some implicated in development, transcription, cell metabolism and signal transduction, are differentially regulated including down-regulation of several genes necessary for GABA-mediated signaling. These findings identify a collection of gene transcripts that may be responsible for the abnormal electrical discharge and epileptic activities observed in a mind bomb zebrafish mutant. This work may have important implications for neurological and neurodevelopmental disorders associated with mutations in ubiquitin ligase activity. Notch is an essential component of an evolutionarily

  3. Reduced spontaneous neuronal activity in the insular cortex and thalamus in healthy adults with insomnia symptoms.

    PubMed

    Liu, Chun-Hong; Liu, Cun-Zhi; Zhang, Jihui; Yuan, Zhen; Tang, Li-Rong; Tie, Chang-Le; Fan, Jin; Liu, Qing-Quan

    2016-10-01

    Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. EEG background activity is abnormal in the temporal and inferior parietal cortex in benign rolandic epilepsy of childhood: a LORETA study.

    PubMed

    Besenyei, M; Varga, E; Fekete, I; Puskás, S; Hollódy, K; Fogarasi, A; Emri, M; Opposits, G; Kis, S A; Clemens, B

    2012-01-01

    Benign rolandic epilepsy of childhood (BERS) is an epilepsy syndrome with presumably genetic-developmental etiology. The pathological basis of this syndrome is completely unknown. We postulated that a developmental abnormality presumably results in abnormal EEG background activity findings. 20 children with typical BERS and an age- and sex-matched group of healthy control children underwent EEG recording and analysis. 60×2 s epochs of waking EEG background activity (without epileptiform potentials and artifacts) were analyzed in the 1-25 Hz frequency range, in very narrow bands (VNB, 1 Hz bandwidth). LORETA (Low Resolution Electromagnetic Tomography) localized multiple distributed sources of EEG background activity in the Talairach space. LORETA activity (current source density) was computed for 2394 voxels and 25 VNBs. Normalized LORETA data were processed to voxel-wise comparison between the BERS and control groups. Bonferroni-corrected p<0.05 Student's t-values were accepted as statistically significant. Increased LORETA activity was found in the BERS group (as compared to the controls) in the left and right temporal lobes (fusiform gyri, posterior parts of the superior, middle and inferior temporal gyri) and in the angular gyri in the parietal lobes, in the 4-6 Hz VNBs, mainly at 5 Hz. (1) Areas of abnormal LORETA activity exactly correspond to the temporal and parietal cortical areas that are major components of the Mirsky attention model and also the perisylvian speech network. Thus the LORETA findings may correspond to impaired attention and speech in BERS patients. (2) The LORETA findings may contribute to delineating the epileptic network in BERS. The novel findings may contribute to investigating neuropsychological disturbances and organization of the epileptic network in BERS. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Penttinen, Kirsi; Siirtola, Harri; Àvalos-Salguero, Jorge; Vainio, Tiina; Juhola, Martti; Aalto-Setälä, Katriina

    2015-01-01

    Comprehensive functioning of Ca2+ cycling is crucial for excitation–contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs. PMID:26308621

  6. Novel Analysis Software for Detecting and Classifying Ca2+ Transient Abnormalities in Stem Cell-Derived Cardiomyocytes.

    PubMed

    Penttinen, Kirsi; Siirtola, Harri; Àvalos-Salguero, Jorge; Vainio, Tiina; Juhola, Martti; Aalto-Setälä, Katriina

    2015-01-01

    Comprehensive functioning of Ca2+ cycling is crucial for excitation-contraction coupling of cardiomyocytes (CMs). Abnormal Ca2+ cycling is linked to arrhythmogenesis, which is associated with cardiac disorders and heart failure. Accordingly, we have generated spontaneously beating CMs from induced pluripotent stem cells (iPSC) derived from patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), which is an inherited and severe cardiac disease. Ca2+ cycling studies have revealed substantial abnormalities in these CMs. Ca2+ transient analysis performed manually lacks accepted analysis criteria, and has both low throughput and high variability. To overcome these issues, we have developed a software tool, AnomalyExplorer based on interactive visualization, to assist in the classification of Ca2+ transient patterns detected in CMs. Here, we demonstrate the usability and capability of the software, and we also compare the analysis efficiency to manual analysis. We show that AnomalyExplorer is suitable for detecting normal and abnormal Ca2+ transients; furthermore, this method provides more defined and consistent information regarding the Ca2+ abnormality patterns and cell line specific differences when compared to manual analysis. This tool will facilitate and speed up the analysis of CM Ca2+ transients, making it both more accurate and user-independent. AnomalyExplorer can be exploited in Ca2+ cycling analysis to study basic disease pathology and the effects of different drugs.

  7. Ziprasidone-induced spontaneous orgasm.

    PubMed

    Boora, K; Chiappone, K; Dubovsky, S; Xu, J

    2010-06-01

    Neuroleptic treatment in schizophrenic patients has been associated with sexual dysfunction, including impotence and decreased libido. Spontaneous ejaculation without sexual arousal during typical antipsychotic treatment is a rare condition that has been described with zuclopentixol, trifluoperazine, and thiothixene. Here, we are reporting a case of spontaneous orgasm with ziprasidone in a bipolar patient. This patient began to repeatedly experience spontaneous sexual arousal and orgasm, which she had never experienced in the past. Ziprasidone might be causing an increase in sexual orgasm by 5-HT2 receptor antagonism, which preclinical evidence suggests that it facilitates dopamine release in the cortex.

  8. Intelligence-related differences in the asymmetry of spontaneous cerebral activity.

    PubMed

    Santarnecchi, Emiliano; Tatti, Elisa; Rossi, Simone; Serino, Vinicio; Rossi, Alessandro

    2015-09-01

    Recent evidence suggests the spontaneous BOLD signal synchronization of corresponding interhemispheric, homotopic regions as a stable trait of human brain physiology, with emerging differences in such organization being also related to some pathological conditions. To understand whether such brain functional symmetries play a role into higher-order cognitive functioning, here we correlated the functional homotopy profiles of 119 healthy subjects with their intelligence level. Counterintuitively, reduced homotopic connectivity in above average-IQ versus average-IQ subjects was observed, with significant reductions in visual and somatosensory cortices, supplementary motor area, rolandic operculum, and middle temporal gyrus, possibly suggesting that a downgrading of interhemispheric talk at rest could be associated with higher cognitive functioning. These regions also showed an increased spontaneous synchrony with medial structures located in ipsi- and contralateral hemispheres, with such pattern being mostly detectable for regions placed in the left hemisphere. The interactions with age and gender have been also tested, with different patterns for subjects above and below 25 years old and less homotopic connectivity in the prefrontal cortex and posterior midline regions in female participants with higher IQ scores. These findings support prior evidence suggesting a functional role for homotopic connectivity in human cognitive expression, promoting the reduction of synchrony between primary sensory regions as a predictor of higher intelligence levels. © 2015 Wiley Periodicals, Inc.

  9. Spontaneous Chronic Pain After Experimental Thoracotomy Revealed by Conditioned Place Preference: Morphine Differentiates Tactile Evoked Pain From Spontaneous Pain.

    PubMed

    Hung, Ching-Hsia; Wang, Jeffrey Chi-Fei; Strichartz, Gary R

    2015-09-01

    Chronic pain after surgery limits social activity, interferes with work, and causes emotional suffering. A major component of such pain is reported as resting or spontaneous pain with no apparent external stimulus. Although experimental animal models can simulate the stimulus-evoked chronic pain that occurs after surgery, there have been no studies of spontaneous chronic pain in such models. Here the conditioned place preference (CPP) paradigm was used to reveal resting pain after experimental thoracotomy. Male Sprague Dawley rats received a thoracotomy with 1-hour rib retraction, resulting in evoked tactile hypersensitivity, previously shown to last for at least 9 weeks. Intraperitoneal injections of morphine (2.5 mg/kg) or gabapentin (40 mg/kg) gave equivalent 2- to 3-hour-long relief of tactile hypersensitivity when tested 12 to 14 days postoperatively. In separate experiments, single trial CPP was conducted 1 week before thoracotomy and then 12 days (gabapentin) or 14 days (morphine) after surgery, followed the next day by 1 conditioning session with morphine or gabapentin, both versus saline. The gabapentin-conditioned but not the morphine-conditioned rats showed a significant preference for the analgesia-paired chamber, despite the equivalent effect of the 2 agents in relieving tactile allodynia. These results show that experimental thoracotomy in rats causes spontaneous pain and that some analgesics, such as morphine, that reduce evoked pain do not also relieve resting pain, suggesting that pathophysiological mechanisms differ between these 2 aspects of long-term postoperative pain. Perspective: Spontaneous pain, a hallmark of chronic postoperative pain, is demonstrated here in a rat model of experimental postthoracotomy pain, further validating the use of this model for the development of analgesics to treat such symptoms. Although stimulus-evoked pain was sensitive to systemic morphine, spontaneous pain was not, suggesting different mechanistic

  10. Are barriers to physical activity similar for adults with and without abnormal glucose metabolism?

    PubMed

    Hume, Clare; Dunstan, David; Salmon, Jo; Healy, Genevieve; Andrianopoulos, Nick; Owen, Neville

    2010-01-01

    The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged > or =25 years. AGM was identified through an oral glucose tolerance test. The previous week's physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Of the 7088 participants (47.5 +/- 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P < .001). Key barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

  11. Spontaneous Ad Hoc Mobile Cloud Computing Network

    PubMed Central

    Lacuesta, Raquel; Sendra, Sandra; Peñalver, Lourdes

    2014-01-01

    Cloud computing helps users and companies to share computing resources instead of having local servers or personal devices to handle the applications. Smart devices are becoming one of the main information processing devices. Their computing features are reaching levels that let them create a mobile cloud computing network. But sometimes they are not able to create it and collaborate actively in the cloud because it is difficult for them to build easily a spontaneous network and configure its parameters. For this reason, in this paper, we are going to present the design and deployment of a spontaneous ad hoc mobile cloud computing network. In order to perform it, we have developed a trusted algorithm that is able to manage the activity of the nodes when they join and leave the network. The paper shows the network procedures and classes that have been designed. Our simulation results using Castalia show that our proposal presents a good efficiency and network performance even by using high number of nodes. PMID:25202715

  12. Inconsistencies in spontaneous and intentional trait inferences.

    PubMed

    Ma, Ning; Vandekerckhove, Marie; Baetens, Kris; Van Overwalle, Frank; Seurinck, Ruth; Fias, Wim

    2012-11-01

    This study explores the fMRI correlates of observers making trait inferences about other people under conflicting social cues. Participants were presented with several behavioral descriptions involving an agent that implied a particular trait. The last behavior was either consistent or inconsistent with the previously implied trait. This was done under instructions that elicited either spontaneous trait inferences ('read carefully') or intentional trait inferences ('infer a trait'). The results revealed that when the behavioral descriptions violated earlier trait implications, regardless of instruction, the medial prefrontal cortex (mPFC) was more strongly recruited as well as the domain-general conflict network including the posterior medial frontal cortex (pmFC) and the right prefrontal cortex (rPFC). These latter two areas were more strongly activated under intentional than spontaneous instructions. These findings suggest that when trait-relevant behavioral information is inconsistent, not only is activity increased in the mentalizing network responsible for trait processing, but control is also passed to a higher level conflict monitoring network in order to detect and resolve the contradiction.

  13. Early physiological abnormalities after simian immunodeficiency virus infection.

    PubMed

    Horn, T F; Huitron-Resendiz, S; Weed, M R; Henriksen, S J; Fox, H S

    1998-12-08

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

  14. Spontaneous Thought and Vulnerability to Mood Disorders: The Dark Side of the Wandering Mind.

    PubMed

    Marchetti, Igor; Koster, Ernst H W; Klinger, Eric; Alloy, Lauren B

    2016-09-01

    There is increasing interest in spontaneous thought, namely task-unrelated or rest-related mental activity. Spontaneous thought is an umbrella term for processes like mindwandering, involuntary autobiographical memory, and daydreaming, with evidence elucidating adaptive and maladaptive consequences. In this theoretical framework, we propose that, apart from its positive functions, spontaneous thought is a precursor for cognitive vulnerability in individuals who are at-risk for mood disorders. Importantly, spontaneous thought mostly focuses on unattained goals and evaluates the discrepancy between current and desired status (Klinger, 1971, 2013a). In individuals who stably (i.e., trait negative affectivity) or transitorily (i.e., stress) experience negative emotions in reaction to goal-discrepancy, spontaneous thought fosters major cognitive vulnerabilities (e.g., rumination, hopelessness, low self-esteem, and cognitive reactivity) which, in turn, enhance depression. Furthermore, we also highlight preliminary links between spontaneous thought and bipolar disorder. The evidence for this framework is reviewed and we discuss theoretical and clinical implications of our proposal.

  15. Spontaneous Thought and Vulnerability to Mood Disorders: The Dark Side of the Wandering Mind

    PubMed Central

    Marchetti, Igor; Koster, Ernst H.W.; Klinger, Eric; Alloy, Lauren B.

    2017-01-01

    There is increasing interest in spontaneous thought, namely task-unrelated or rest-related mental activity. Spontaneous thought is an umbrella term for processes like mindwandering, involuntary autobiographical memory, and daydreaming, with evidence elucidating adaptive and maladaptive consequences. In this theoretical framework, we propose that, apart from its positive functions, spontaneous thought is a precursor for cognitive vulnerability in individuals who are at-risk for mood disorders. Importantly, spontaneous thought mostly focuses on unattained goals and evaluates the discrepancy between current and desired status (Klinger, 1971, 2013a). In individuals who stably (i.e., trait negative affectivity) or transitorily (i.e., stress) experience negative emotions in reaction to goal-discrepancy, spontaneous thought fosters major cognitive vulnerabilities (e.g., rumination, hopelessness, low self-esteem, and cognitive reactivity) which, in turn, enhance depression. Furthermore, we also highlight preliminary links between spontaneous thought and bipolar disorder. The evidence for this framework is reviewed and we discuss theoretical and clinical implications of our proposal. PMID:28785510

  16. [Glucooxidative stress and spontaneous abortion in pregnant women with diabetes mellitus type 1].

    PubMed

    Todorova, K; Ivanov, S; Mazneĭkova, V; Genova, M

    2005-01-01

    The pregnancies in women with Diabetes mellitus are in condition of increased glucooxidative stress, which could be toxic for the developing embryo. END-POINTS: To evaluate the levels of selenium and glutation peroxidase in pregnant women with Diabetes mellitus type 1 in the first trimester of pregnancy and to establish whether there is a correlation between the diabetic glycemic control and occurrence of spontaneous abortions. Prospective study of 75 women for 1 year period. he pregnant women were divided in 3 groups as follows: 1st group--30 pregnant women with Diabetes mellitus type 1 with normal outcome; 2nd group--16 pregnant women with Diabetes mellitus type 1 with spontaneous abortion; 3rd group--29 healthy pregnant controls. The activity of GI-Px in red blood cells was measured in hemolysat of EDTA plasma in Germany. The levels of glucosylated haemoglobin were also evaluated. 1. In all pregnant women the levels of selenium were lower without significant difference between them 1st group--0.12 +/- 0.6 mmol/l, 2ndd group 0.13 +/- 0.1 mmol/l, 3rd group 0.13 +/- 0.7 mmol/l (P > 0.05). 2. There is an increase in the activity of GI-Px, which is statistically significant in the healthy pregnant women 47.8 +/- 13.3 U/g Hb and diabetic pregnant women with normal outcome 48. 6 +/- 8.4 U/g Hb. There is no statistically significant difference in the activity of GI-Px in diabetic pregnant women with spontaneous abortions and the healthy controls (P > 0. 05). 3. Negative correlation between the levels of selenium and the activity of GI-Px was proved in healthy pregnant women (r = - 0.4; P < 0.05). No correlation was found between the level of the selenium and the activity of GI-Px into the two groups of diabetic pregnant women. 4. There is a correlation in the levels of diabetic pregnant women with spontaneous abortions (r = -0.38; P < 0.001). The increased activity of GI-Px in diabetic pregnant women with spontaneous abortions is a result of increased antioxidative

  17. Meiotic abnormalities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  18. Being Spontaneous: The Future of Telehealth Implementation?

    PubMed

    Mars, Maurice; Scott, Richard E

    2017-09-01

    The smartphone simplifies interprofessional communication, and smartphone applications can facilitate telemedicine activity. Much has been written about the steps that need to be followed to implement and establish a successful telemedicine service that is integrated into everyday clinical practice. A traditional and systematic approach has evolved incorporating activities such as strategy development, needs assessment, business cases and plans, readiness assessment, implementation plans, change management interventions, and ongoing monitoring and evaluation. This "best practice" has been promoted in the telehealth literature for many years. In contrast, several recent initiatives have arisen without any such formal undertakings. This article describes the strengths and weaknesses of two "spontaneous" telemedicine services in dermatology and burn management that have evolved in South Africa. Two spontaneous services were identified and reviewed. In one unsolicited service, doctors at rural referring hospitals have been taking photographs of skin lesions and sending them with a brief text message history to dermatologists using the instant messaging smartphone app, WhatsApp. In the other, burns service, admissions to the burns unit or the clinic were triaged by telephonic description of the case and completion of a preadmission questionnaire. More recently, management and referral decisions are made only after completion of the questionnaire and subsequent submission of photographs of the burn sent by WhatsApp, with the decision transmitted by text message. Although efficient and effective, potential legal and ethical shortcomings have been identified. These "spontaneous" telehealth services challenge traditional best practice, yet appear to lead to truly integrated practice and, therefore, are successful and warrant further study.

  19. Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: Disruptive effect of cocaine

    PubMed Central

    Larson, Alice A.; Thomas, Mark J.; McElhose, Alex; Kovács, Katalin J.

    2011-01-01

    Mast cells are located in the central nervous system (CNS) of many mammals and stress induces their degranulation. We postulated that mast cells are associated with wakefulness and stimulatory tone in the CNS, as reflected by spontaneous motor activity. Because stress also precipitates drug-seeking behavior in cocaine addicts, we also postulated that cocaine manifests its effects through this relationship. We investigated the influence of single and repeated injections of cocaine on circulating corticosterone, motor activity and degranulation of mast cells in both the thalamus and meninges of mice. Mice were subjected to 5 consecutive days of cocaine or saline followed by a single injection of cocaine or saline 11 days later. Spontaneous locomotor activity was measure for one hour after the final injection before death. Neither a single injection nor prior treatment with cocaine increased motor activity compared to saline-injected controls, however, repeated administration of cocaine induced a significant sensitization to its behavioral effect when delivered 11 days later. In mice that received only saline, motor activity correlated positively with mast cell degranulation in the meninges but not in the thalamus. Cocaine, regardless of the treatment schedule, disrupted this correlation. The concentration of corticosterone did not differ amongst groups and did not correlate with either behavior or mast cell parameters in any group. The correlation between behavioral activity and the mast cell degranulation in the meninges suggests that these parameters are linked. The disruptive effect of cocaine on this relationship indicates a role downstream from mast cells in the regulation of motor activity. PMID:21561602

  20. Gender differences in brain activity and the relationship between brain activity and differences in prevalence rates between male and female major depressive disorder patients: a resting-state fMRI study.

    PubMed

    Yao, Zhijian; Yan, Rui; Wei, Maobin; Tang, Hao; Qin, Jiaolong; Lu, Qing

    2014-11-01

    We examined the gender-difference effect on abnormal spontaneous neuronal activity of male and female major depressive disorder (MDD) patients using the amplitude of low-frequency fluctuation (ALFF) and the further clarified the relationship between the abnormal ALFF and differences in MDD prevalence rates between male and female patients. Fourteen male MDD patients, 13 female MDD patients and 15 male and 15 female well matched healthy controls (HCs) completed this study. The ALFF approach was used, and Pearson correlation was conducted to observe a possible clinical relevance. There were widespread differences in ALFF values between female and male MDD patients, including some important parts of the frontoparietal network, auditory network, attention network and cerebellum network. In female MDD patients, there was a positive correlation between average ALFF values of the left postcentral gyrus and the severity of weight loss symptom. The gender-difference effect leading to abnormal brain activity is an important underlying pathomechanism for different somatic symptoms in MDD patients of different genders and is likely suggestive of higher MDD prevalence rates in females. The abnormal ALFF resulting from the gender-difference effect might improve our understanding of the differences in prevalence rates between male and female MDD patients from another perspective. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Associations of recurrent miscarriages with chromosomal abnormalities, thrombophilia allelic polymorphisms and/or consanguinity in Saudi Arabia.

    PubMed

    Turki, Rola F; Assidi, Mourad; Banni, Huda A; Zahed, Hanan A; Karim, Sajjad; Schulten, Hans-Juergen; Abu-Elmagd, Muhammad; Rouzi, Abdulrahim A; Bajouh, Osama; Jamal, Hassan S; Al-Qahtani, Mohammed H; Abuzenadah, Adel M

    2016-10-10

    Recurrent pregnancy loss (RPL) or recurrent spontaneous abortion is an obstetric complication that affects couples at reproductive age. Previous reports documented a clear relationship between parents with chromosomal abnormalities and both recurrent miscarriages and infertility. However, limited data is available from the Arabian Peninsula which is known by higher rates of consanguineous marriages. The main goal of this study was to determine the prevalence of chromosomal abnormalities and thrombophilic polymorphisms, and to correlate them with RPL and consanguinity in Saudi Arabia. Cytogenetic analysis of 171 consent patients with RPL was performed by the standard method of 72-h lymphocyte culture and GTG banding. Allelic polymorphisms of three thrombophilic genes (Factor V Leiden, Prothrombin A20210G, MTHFR C677T) were performed using PCR-RFLP (restriction fragment length polymorphism) and gel electrophoresis. Data analysis revealed that 7.6 % of patients were carrier of numerical or structural chromosomal abnormalities. A high rate of translocations (46 %) was associated to increased incidence of RPL. A significant correlation between consanguineous RPL patients and chromosomal abnormalities (P < 0.05) was found. Both Factor V Leiden and Prothrombin A20210G allelic polymorphisms were significantly associated with a higher prevalence of RPL. This study demonstrated a strong association between RPL and the prevalence of chromosomal abnormalities and inherited thrombophilia. Given the high rate of consanguineous marriages in the Saudi population, these results underline the importance of systematic cytogenetic investigation and genetic counseling preferably at the premarital stage or at least during early pregnancy phase through preimplantation genetic diagnosis (PGD).

  2. Rapid spontaneous cerebrospinal fluid leak detected in the gastrointestinal tract.

    PubMed

    Ma, Hong Yun; Sen, Papia; Stein, Evan G; Freeman, Leonard M

    2014-02-01

    There are many causes of cerebrospinal (CSF) leaks. Most cases are secondary to blunt trauma and iatrogenic trauma caused by postoperative sequelae. Occasionally, CSF leakage may occur from nontraumatic or "spontaneous" causes, such as benign intracranial hypertension and "empty sella syndrome." Mass effect due to an encephalocele or meningocele may also be seen. Radionuclide cisternography is a sensitive method of determining CSF leak when combined with intranasal cotton pledget placement and analysis. We present a spontaneous CSF fluid leak that was detected when scintigraphic activity appeared first in the gastrointestinal tract.

  3. From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model

    PubMed Central

    Marques, Hugo Gravato; Bharadwaj, Arjun; Iida, Fumiya

    2014-01-01

    In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions. PMID:25057775

  4. Glial activation colocalizes with structural abnormalities in amyotrophic lateral sclerosis

    PubMed Central

    Alshikho, Mohamad J.; Zürcher, Nicole R.; Loggia, Marco L.; Cernasov, Paul; Chonde, Daniel B.; Izquierdo Garcia, David; Yasek, Julia E.; Akeju, Oluwaseun; Catana, Ciprian; Rosen, Bruce R.; Cudkowicz, Merit E.

    2016-01-01

    Objective: In this cross-sectional study, we aimed to evaluate brain structural abnormalities in relation to glial activation in the same cohort of participants. Methods: Ten individuals with amyotrophic lateral sclerosis (ALS) and 10 matched healthy controls underwent brain imaging using integrated MR/PET and the radioligand [11C]-PBR28. Diagnosis history and clinical assessments including Upper Motor Neuron Burden Scale (UMNB) were obtained from patients with ALS. Diffusion tensor imaging (DTI) analyses including tract-based spatial statistics and tractography were applied. DTI metrics including fractional anisotropy (FA) and diffusivities (mean, axial, and radial) were measured in regions of interest. Cortical thickness was assessed using surface-based analysis. The locations of structural changes, measured by DTI and the areas of cortical thinning, were compared to regional glial activation measured by relative [11C]-PBR28 uptake. Results: In this cohort of individuals with ALS, reduced FA and cortical thinning colocalized with regions demonstrating higher radioligand binding. [11C]-PBR28 binding in the left motor cortex was correlated with FA (r = −0.68, p < 0.05) and cortical thickness (r = −0.75, p < 0.05). UMNB was correlated with glial activation (r = +0.75, p < 0.05), FA (r = −0.77, p < 0.05), and cortical thickness (r = −0.75, p < 0.05) in the motor cortex. Conclusions: Increased uptake of the glial marker [11C]-PBR28 colocalizes with changes in FA and cortical thinning. This suggests a link between disease mechanisms (gliosis and inflammation) and structural changes (cortical thinning and white and gray matter changes). In this multimodal neuroimaging work, we provide an in vivo model to investigate the pathogenesis of ALS. PMID:27837005

  5. Abnormal branching and regression of the notochord and its relationship to foregut abnormalities.

    PubMed

    Vleesch Dubois, V N; Quan Qi, B; Beasley, S W; Williams, A

    2002-04-01

    An abnormally positioned notochord has been reported in embryos that develop foregut abnormalities, vertebral defects and other abnormalities of the VATER association. This study examines the patterns of regression of the abnormal notochord in the rat model of the VATER association and investigates the relationship between developmental abnormalities of the notochord and those of the vertebra and foregut. Timed-pregnant Sprague-Dawley rats were given daily intraperitoneal injections of 1.75 mg/kg adriamycin on gestational days 6 - 9 inclusive. Rats were sacrificed between days 14 and 20 and their embryos harvested, histologically sectioned and stained and examined serially. The location and appearance of the degenerating notochord and its relationship to regional structural defects were analysed. All 26 embryos exposed to adriamycin developed foregut abnormalities and had an abnormal notochord. The notochord disappeared by a process of apoptotic degeneration that lagged behind that of the normal embryo: the notochord persisted in the abnormal embryo beyond day 17, whereas in the normal rat it had already disappeared. Similarly, formation of the nucleus pulposus was delayed. Vertebral abnormalities occurred when the notochord was ventrally-positioned. The notochord disappears during day 16 in the normal embryo whereas abnormal branches of the notochord persist until day 19 in the adriamycin-treated embryo. Degeneration of the notochord is dominated by apoptosis. An excessively ventrally-placed notochord is closely associated with abnormalities of the vertebral column, especially hemivertebrae.

  6. Human Papillomavirus Infection as a Possible Cause of Spontaneous Abortion and Spontaneous Preterm Delivery

    PubMed Central

    Ambühl, Lea Maria Margareta; Baandrup, Ulrik; Dybkær, Karen; Blaakær, Jan; Uldbjerg, Niels; Sørensen, Suzette

    2016-01-01

    Based on the current literature, we aimed to provide an overview on Human Papillomavirus prevalence in normal pregnancies and pregnancies with adverse outcome. We conducted a systematic literature search in PubMed and Embase. Data extracted from the articles and used for analysis included HPV prevalence, pregnancy outcome, geographical location, investigated tissue types, and HPV detection methods. The overall HPV prevalence in normal full-term pregnancies was found to be 17.5% (95% CI; 17.3–17.7) for cervix, 8.3% (95% CI; 7.6–9.1) for placental tissue, 5.7% (95% CI; 5.1–6.3) for amniotic fluid, and 10.9% (95% CI; 10.1–11.7) for umbilical cord blood. Summary estimates for HPV prevalence of spontaneous abortions and spontaneous preterm deliveries, in cervix (spontaneous abortions: 24.5%, and preterm deliveries: 47%, resp.) and placenta (spontaneous abortions: 24.9%, and preterm deliveries: 50%, resp.), were identified to be higher compared to normal full-term pregnancies (P < 0.05 and P < 0.0001). Great variation in HPV prevalence was observed between study populations of different geographical locations. This review demonstrates an association between spontaneous abortion, spontaneous preterm delivery, and the presence of HPV in both the cervix and the placenta. However, a reliable conclusion is difficult to draw due to the limited number of studies conducted on material from pregnancies with adverse outcome and the risk of residual confounding. PMID:27110088

  7. Localization of spontaneous bursting neuronal activity in the preterm human brain with simultaneous EEG-fMRI.

    PubMed

    Arichi, Tomoki; Whitehead, Kimberley; Barone, Giovanni; Pressler, Ronit; Padormo, Francesco; Edwards, A David; Fabrizi, Lorenzo

    2017-09-12

    Electroencephalographic recordings from the developing human brain are characterized by spontaneous neuronal bursts, the most common of which is the delta brush. Although similar events in animal models are known to occur in areas of immature cortex and drive their development, their origin in humans has not yet been identified. Here, we use simultaneous EEG-fMRI to localise the source of delta brush events in 10 preterm infants aged 32-36 postmenstrual weeks. The most frequent patterns were left and right posterior-temporal delta brushes which were associated in the left hemisphere with ipsilateral BOLD activation in the insula only; and in the right hemisphere in both the insular and temporal cortices. This direct measure of neural and hemodynamic activity shows that the insula, one of the most densely connected hubs in the developing cortex, is a major source of the transient bursting events that are critical for brain maturation.

  8. Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats

    PubMed Central

    Perez-Leighton, Claudio; Grace, Martha; Billington, Charles J.; Kotz, Catherine M.

    2015-01-01

    Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement can promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN. PMID:24912135

  9. Role of spontaneous physical activity in prediction of susceptibility to activity based anorexia in male and female rats.

    PubMed

    Perez-Leighton, Claudio E; Grace, Martha; Billington, Charles J; Kotz, Catherine M

    2014-08-01

    Anorexia nervosa (AN) is a chronic eating disorder affecting females and males, defined by body weight loss, higher physical activity levels and restricted food intake. Currently, the commonalities and differences between genders in etiology of AN are not well understood. Animal models of AN, such as activity-based anorexia (ABA), can be helpful in identifying factors determining individual susceptibility to AN. In ABA, rodents are given an access to a running wheel while food restricted, resulting in paradoxical increased physical activity levels and weight loss. Recent studies suggest that different behavioral traits, including voluntary exercise, can predict individual weight loss in ABA. A higher inherent drive for movement may promote development and severity of AN, but this hypothesis remains untested. In rodents and humans, drive for movement is defined as spontaneous physical activity (SPA), which is time spent in low-intensity, non-volitional movements. In this paper, we show that a profile of body weight history and behavioral traits, including SPA, can predict individual weight loss caused by ABA in male and female rats with high accuracy. Analysis of the influence of SPA on ABA susceptibility in males and females rats suggests that either high or low levels of SPA increase the probability of high weight loss in ABA, but with larger effects in males compared to females. These results suggest that the same behavioral profile can identify individuals at-risk of AN for both male and female populations and that SPA has predictive value for susceptibility to AN. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Spontaneous sternocleidomastoid muscle hematoma following thrombolysis for acute ischemic stroke.

    PubMed

    Giannantoni, Nadia Mariagrazia; Della Marca, Giacomo; Broccolini, Aldobrando; Pilato, Fabio; Profice, Paolo; Morosetti, Roberta; Caliandro, Pietro; Frisullo, Giovanni

    2014-06-15

    Spontaneous or traumatic bleeding is a common complication of systemic thrombolysis in patients with acute ischemic stroke. We report the case of an 83 y.o. woman with right facio-brachio-crural hemiparesis, left deviation of the head and aphasia who developed, after thrombolytic therapy, a spontaneous sternocleidomastoid muscle hematoma that regressed few days later. To our knowledge, this is the first case reported in the literature of asymptomatic and spontaneous skeletal muscle hematoma following thrombolysis for the treatment of acute ischemic stroke. The occurrence of lateral cervical tuberculosis lymphadenitis ipsilateral to sternocleidomastoid muscle hematoma may suggest a causal relationship between local chronic inflammation of active mycobacterial infection and thrombolysis-related extravasation. This case should suggest caution in thrombolytic treatment in patients with chronic immune dysregulation and vascular inflammation such as extra-pulmonary tuberculosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Spontaneous rib fractures.

    PubMed

    Katrancioglu, Ozgur; Akkas, Yucel; Arslan, Sulhattin; Sahin, Ekber

    2015-07-01

    Other than trauma, rib fracture can occur spontaneously due to a severe cough or sneeze. In this study, patients with spontaneous rib fractures were analyzed according to age, sex, underlying pathology, treatment, and complications. Twelve patients who presented between February 2009 and February 2011 with spontaneous rib fracture were reviewed retrospectively. The patients' data were evaluated according to anamnesis, physical examination, and chest radiographs. The ages of the patients ranged from 34 to 77 years (mean 55.91 ± 12.20 years), and 7 (58.4%) were male. All patients had severe cough and chest pain. The fractures were most frequently between 4th and 9th ribs; multiple rib fractures were detected in 5 (41.7%) patients. Eight (66.7%) patients had chronic obstructive pulmonary disease, 2 (16.7%) had bronchial asthma, and 2 (16.7%) had osteoporosis. Bone densitometry revealed a high risk of bone fracture in all patients. Patients with chronic obstructive pulmonary disease or bronchial asthma had been treated with high-dose steroids for over a year. Spontaneous rib fracture due to severe cough may occur in patients with osteoporosis, chronic obstructive pulmonary disease, or bronchial asthma, receiving long-term steroid therapy. If these patients have severe chest pain, chest radiography should be performed to check for bone lesions. © The Author(s) 2015.

  12. Spontaneous Trigeminal Allodynia in Rats: A Model of Primary Headache

    PubMed Central

    Oshinsky, Michael L.; Sanghvi, Menka M.; Maxwell, Christina R.; Gonzalez, Dorian; Spangenberg, Rebecca J.; Cooper, Marnie; Silberstein, Stephen D.

    2014-01-01

    Animal models are essential for studying the pathophysiology of headache disorders and as a screening tool for new therapies. Most animal models modify a normal animal in an attempt to mimic migraine symptoms. They require manipulation to activate the trigeminal nerve or dural nociceptors. At best, they are models of secondary headache. No existing model can address the fundamental question: How is a primary headache spontaneously initiated? In the process of obtaining baseline periorbital von Frey thresholds in a wild-type Sprague-Dawley rat, we discovered a rat with spontaneous episodic trigeminal allodynia (manifested by episodically changing periorbital pain threshold). Subsequent mating showed that the trait is inherited. Animals with spontaneous trigeminal allodynia allow us to study the pathophysiology of primary recurrent headache disorders. To validate this as a model for migraine, we tested the effects of clinically proven acute and preventive migraine treatments on spontaneous changes in rat periorbital sensitivity. Sumatriptan, ketorolac, and dihydroergotamine temporarily reversed the low periorbital pain thresholds. Thirty days of chronic valproic acid treatment prevented spontaneous changes in trigeminal allodynia. After discontinuation, the rats returned to their baseline of spontaneous episodic threshold changes. We also tested the effects of known chemical human migraine triggers. On days when the rats did not have allodynia and showed normal periorbital von Frey thresholds, glycerol trinitrate and calcitonin gene related peptide induced significant decreases in the periorbital pain threshold. This model can be used as a predictive model for drug development and for studies of putative biomarkers for headache diagnosis and treatment. PMID:22963523

  13. Spontaneous Release Regulates Synaptic Scaling in the Embryonic Spinal Network In Vivo

    PubMed Central

    Garcia-Bereguiain, Miguel Angel; Gonzalez-Islas, Carlos; Lindsly, Casie

    2016-01-01

    Homeostatic plasticity mechanisms maintain cellular or network spiking activity within a physiologically functional range through compensatory changes in synaptic strength or intrinsic cellular excitability. Synaptic scaling is one form of homeostatic plasticity that is triggered after blockade of spiking or neurotransmission in which the strengths of all synaptic inputs to a cell are multiplicatively scaled upward or downward in a compensatory fashion. We have shown previously that synaptic upscaling could be triggered in chick embryo spinal motoneurons by complete blockade of spiking or GABAA receptor (GABAAR) activation for 2 d in vivo. Here, we alter GABAAR activation in a more physiologically relevant manner by chronically adjusting presynaptic GABA release in vivo using nicotinic modulators or an mGluR2 agonist. Manipulating GABAAR activation in this way triggered scaling in a mechanistically similar manner to scaling induced by complete blockade of GABAARs. Remarkably, we find that altering action-potential (AP)-independent spontaneous release was able to fully account for the observed bidirectional scaling, whereas dramatic changes in spiking activity associated with spontaneous network activity had little effect on quantal amplitude. The reliance of scaling on an AP-independent process challenges the plasticity's relatedness to spiking in the living embryonic spinal network. Our findings have implications for the trigger and function of synaptic scaling and suggest that spontaneous release functions to regulate synaptic strength homeostatically in vivo. SIGNIFICANCE STATEMENT Homeostatic synaptic scaling is thought to prevent inappropriate levels of spiking activity through compensatory adjustments in the strength of synaptic inputs. Therefore, it is thought that perturbations in spike rate trigger scaling. Here, we find that dramatic changes in spiking activity in the embryonic spinal cord have little effect on synaptic scaling; conversely, alterations in

  14. Effect of insulin on spontaneous and progesterone-induced GVBD on Bufo arenarum denuded oocytes.

    PubMed

    Sánchez Toranzo, G; Bonilla, F; Zelarayán, L; Oterino, J; Bühler, M I

    2004-08-01

    Progesterone is considered as the physiological steroid hormone that triggers meiosis reinitiation in amphibian oocytes. Nevertheless, isolated oocytes can be induced to undergo germinal vesicle breakdown (GVBD) in a saline medium by means of treatment with various hormones or inducing agents such as other steroid hormones, insulin or an insulin-like growth factor. It has been demonstrated that Bufo arenarum oocytes obtained during the reproductive period (spring-summer) resume meiosis with no need of an exogenous hormonal stimulus if deprived of their enveloping follicle cells, a phenomenon called spontaneous maturation. This study was undertaken to evaluate the participation of the purine and phosphoinositide pathway in the insulin-induced maturation of oocytes competent and incompetent to mature spontaneously, as well as to determine whether the activation of the maturation promoting factor (MPF) involved the activation of cdc25 phosphatase in Bufo arenarum denuded oocytes. Our results indicate that insulin was able to induce GBVD in oocytes incompetent to mature spontaneously and to enhance spontaneous and progesterone-induced maturation. In addition, high intracellular levels of purines such as cAMP or guanosine can reversibly inhibit the progesterone and insulin-induced maturation process in Bufo arenarum as well as spontaneous maturation. Assays of the inhibition of phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and its turnover by neomycin and lithium chloride respectively exhibited a different response in insulin- or progesterone-treated oocytes, suggesting that phosphoinositide turnover or hydrolysis of PIP2 is involved in progesterone- but not in insulin-induced maturation. In addition, the inhibitory effect of vanadate suggests that an inactive pre-maturation promoting factor (pre-MPF), activated by dephosphorylation of Thr-14 and Tyr-15 on p34cdc2, is present in Bufo arenarum full-grown oocytes; this step would be common to both spontaneous

  15. Early physiological abnormalities after simian immunodeficiency virus infection

    PubMed Central

    Horn, Thomas F. W.; Huitron-Resendiz, Salvador; Weed, Michael R.; Henriksen, Steven J.; Fox, Howard S.

    1998-01-01

    Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction. PMID:9844017

  16. Cognitive impairment and spontaneous epilepsy in rats with malformations of cortical development.

    PubMed

    Ye-wei, Xiao; Rong, Wang; Xun-tai, Ma; Shan, Zhang; Qian, Chen; Shi-hua, Huang; Fu-qun, Mao; Xiao-ming, Xiong

    2015-12-01

    To examine the cognition, spontaneous epilepsy, and electroencephalography (EEG) characteristics of rats with malformations of cortical development (MCD) and their use as an animal model for investigating the pathogenesis of intractable epilepsy and screening novel antiepileptic drugs. An epileptic rat model of MCD was established with the F1 generation of pregnant rats after X-irradiation with 175 cGy (Group L), 195 cGy (Group M), or 215 cGy (Group H). Long-term video-EEG monitoring was used to record the seizures in the rats with MCD. Cognition was assessed with the Morris water maze. The EEGs were recorded and analyzed in the frontal and parietal lobes and hippocampi of adult rats. Finally, the brain tissues were processed for Nissl staining. The model groups exhibited markedly prolonged escape latencies and distinct decrements in the percent distance traveled in the target quadrant and platform-crossing frequency. These findings were dose-dependent. Frequent interictal epileptiform discharges were observed in the frontal and parietal lobes and hippocampi of adult rats, and their incidences were markedly higher in the model groups compared with that in the normal controls, with Group M having the highest incidence. Spontaneous seizures were observed in the model groups (mean incidence, 46.7%). The daily mean frequency of seizures and the incidence of spontaneous seizures were highest in Group M. Nissl staining revealed a dose-dependent pattern of hippocampal abnormalities, cortical and subcortical nodular heterotopia, and callosal agenesis in the model groups. The 195 cGy dose was most appropriate for establishing an epileptic model of MCD with X-irradiation. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  17. Varenicline and Abnormal Sleep Related Events

    PubMed Central

    Savage, Ruth L.; Zekarias, Alem; Caduff-Janosa, Pia

    2015-01-01

    Study Objectives: To assess adverse drug reaction reports of “abnormal sleep related events” associated with varenicline, a partial agonist to the α4β2 subtype of nicotinic acetylcholine receptors on neurones, indicated for smoking cessation. Design: Twenty-seven reports of “abnormal sleep related events” often associated with abnormal dreams, nightmares, or somnambulism, which are known to be associated with varenicline use, were identified in the World Health Organisation (WHO) Global Individual Case Safety Reports Database. Original anonymous reports were obtained from the four national pharmacovigilance centers that submitted these reports and assessed for reaction description and causality. Measurements and Results: These 27 reports include 10 of aggressive activity occurring during sleep and seven of other sleep related harmful or potentially harmful activities, such as apparently deliberate self-harm, moving a child or a car, or lighting a stove or a cigarette. Assessment of these 17 reports of aggression or other actual or potential harm showed that nine patients recovered or were recovering on varenicline withdrawal and there were no consistent alternative explanations. Thirteen patients experienced single events, and two had multiple events. Frequency was not stated for the remaining two patients. Conclusions: The descriptions of the reports of aggression during sleep with violent dreaming are similar to those of rapid eye movement sleep behavior disorder and also nonrapid eye movement (NREM) sleep parasomnias in some adults. Patients who experience somnambulism or dreams of a violent nature while taking varenicline should be advised to consult their health providers. Consideration should be given to clarifying the term sleep disorders in varenicline product information and including sleep related harmful and potentially harmful events. Citation: Savage RL, Zekarias A, Caduff-Janosa P. Varenicline and abnormal sleep related events. SLEEP 2015

  18. Spontaneous locomotor activity correlates with the degranulation of mast cells in the meninges rather than in the thalamus: disruptive effect of cocaine.

    PubMed

    Larson, Alice A; Thomas, Mark J; McElhose, Alex; Kovács, Katalin J

    2011-06-13

    Mast cells are located in the central nervous system (CNS) of many mammals and stress induces their degranulation. We postulated that mast cells are associated with wakefulness and stimulatory tone in the CNS, as reflected by spontaneous motor activity. Because stress also precipitates drug-seeking behavior in cocaine addicts, we also postulated that cocaine manifests its effects through this relationship. We investigated the influence of single and repeated injections of cocaine on circulating corticosterone, motor activity and degranulation of mast cells in both the thalamus and meninges of mice. Mice were subjected to 5 consecutive days of cocaine or saline followed by a single injection of cocaine or saline 11 days later. Spontaneous locomotor activity was measure for 1h after the final injection before death. Neither a single injection nor prior treatment with cocaine increased motor activity compared to saline-injected controls, however, repeated administration of cocaine induced a significant sensitization to its behavioral effect when delivered 11 days later. In mice that received only saline, motor activity correlated positively with mast cell degranulation in the meninges but not in the thalamus. Cocaine, regardless of the treatment schedule, disrupted this correlation. The concentration of corticosterone did not differ amongst groups and did not correlate with either behavior or mast cell parameters in any group. The correlation between behavioral activity and the mast cell degranulation in the meninges suggests that these parameters are linked. The disruptive effect of cocaine on this relationship indicates a role downstream from mast cells in the regulation of motor activity. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Abnormal neural activities of directional brain networks in patients with long-term bilateral hearing loss.

    PubMed

    Xu, Long-Chun; Zhang, Gang; Zou, Yue; Zhang, Min-Feng; Zhang, Dong-Sheng; Ma, Hua; Zhao, Wen-Bo; Zhang, Guang-Yu

    2017-10-13

    The objective of the study is to provide some implications for rehabilitation of hearing impairment by investigating changes of neural activities of directional brain networks in patients with long-term bilateral hearing loss. Firstly, we implemented neuropsychological tests of 21 subjects (11 patients with long-term bilateral hearing loss, and 10 subjects with normal hearing), and these tests revealed significant differences between the deaf group and the controls. Then we constructed the individual specific virtual brain based on functional magnetic resonance data of participants by utilizing effective connectivity and multivariate regression methods. We exerted the stimulating signal to the primary auditory cortices of the virtual brain and observed the brain region activations. We found that patients with long-term bilateral hearing loss presented weaker brain region activations in the auditory and language networks, but enhanced neural activities in the default mode network as compared with normally hearing subjects. Especially, the right cerebral hemisphere presented more changes than the left. Additionally, weaker neural activities in the primary auditor cortices were also strongly associated with poorer cognitive performance. Finally, causal analysis revealed several interactional circuits among activated brain regions, and these interregional causal interactions implied that abnormal neural activities of the directional brain networks in the deaf patients impacted cognitive function.

  20. Abnormal Motor Activity and Thermoregulation in a Schizophrenia Rat Model for Translational Science

    PubMed Central

    2015-01-01

    Background Schizophrenia is accompanied by altered motor activity and abnormal thermoregulation; therefore, the presence of these symptoms can enhance the face validity of a schizophrenia animal model. The goal was to characterize these parameters in freely moving condition of a new substrain of rats showing several schizophrenia-related alterations. Methods Male Wistar rats were used: the new substrain housed individually (for four weeks) and treated subchronically with ketamine, and naive animals without any manipulations. Adult animals were implanted with E-Mitter transponders intraabdominally to record body temperature and locomotor activity continuously. The circadian rhythm of these parameters and the acute effects of changes in light conditions were analyzed under undisturbed circumstances, and the effects of different interventions (handling, bed changing or intraperitoneal vehicle injection) were also determined. Results Decreased motor activity with fragmented pattern was observed in the new substrain. However, these animals had higher body temperature during the active phase, and they showed wider range of its alterations, too. The changes in light conditions and different interventions produced blunted hyperactivity and altered body temperature responses in the new substrain. Poincaré plot analysis of body temperature revealed enhanced short- and long-term variabilities during the active phase compared to the inactive phase in both groups. Furthermore, the new substrain showed increased short- and long-term variabilities with lower degree of asymmetry suggesting autonomic dysregulation. Conclusions In summary, the new substrain with schizophrenia-related phenomena showed disturbed motor activity and thermoregulation suggesting that these objectively determined parameters can be biomarkers in translational research. PMID:26629908

  1. Intake of probiotic food and risk of spontaneous preterm delivery123

    PubMed Central

    Myhre, Ronny; Brantsæter, Anne Lise; Myking, Solveig; Gjessing, Håkon Kristian; Sengpiel, Verena; Meltzer, Helle Margrete; Haugen, Margaretha; Jacobsson, Bo

    2011-01-01

    Background: Preterm delivery represents a substantial problem in perinatal medicine worldwide. Current knowledge on potential influences of probiotics in food on pregnancy complications caused by microbes is limited. Objective: We hypothesized that intake of food with probiotics might reduce pregnancy complications caused by pathogenic microorganisms and, through this, reduce the risk of spontaneous preterm delivery. Design: This study was performed in the Norwegian Mother and Child Cohort on the basis of answers to a food-frequency questionnaire. We studied intake of milk-based products containing probiotic lactobacilli and spontaneous preterm delivery by using a prospective cohort study design (n = 950 cases and 17,938 controls) for the pregnancy outcome of spontaneous preterm delivery (<37 gestational weeks). Analyses were adjusted for the covariates of parity, maternal educational level, and physical activity. Results: Pregnancies that resulted in spontaneous preterm delivery were associated with any intake of milk-based probiotic products in an adjusted model [odds ratio (OR): 0.857; 95% CI: 0.741, 0.992]. By categorizing intake into none, low, and high intakes of the milk-based probiotic products, a significant association was observed for high intake (OR: 0.820; 95% CI: 0.681, 0.986). Conclusion: Women who reported habitual intake of probiotic dairy products had a reduced risk of spontaneous preterm delivery. PMID:20980489

  2. Hemostatic Abnormalities in Multiple Myeloma Patients

    PubMed Central

    Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

    2018-01-01

    Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

  3. Effects of a high-fat diet on spontaneous metastasis of Lewis lung carcinoma in plasminogen activator inhibitor-1 deficient and wild-type mice

    USDA-ARS?s Scientific Manuscript database

    We investigated the effects of plasminogen activator inhibitor-1 (PAI-1) deficiency on spontaneous metastasis of Lewis lung carcinoma (LLC) in PAI-1 deficient (PAI-1-/-) and wildtype mice (C57BL/6J background) fed the AIN93G diet or that diet modified with 45% calories from fat. The high-fat diet i...

  4. Ultrastructural and cellular basis for the development of abnormal myocardial mechanics during the transition from hypertension to heart failure.

    PubMed

    Shah, Sanjiv J; Aistrup, Gary L; Gupta, Deepak K; O'Toole, Matthew J; Nahhas, Amanda F; Schuster, Daniel; Chirayil, Nimi; Bassi, Nikhil; Ramakrishna, Satvik; Beussink, Lauren; Misener, Sol; Kane, Bonnie; Wang, David; Randolph, Blake; Ito, Aiko; Wu, Megan; Akintilo, Lisa; Mongkolrattanothai, Thitipong; Reddy, Mahendra; Kumar, Manvinder; Arora, Rishi; Ng, Jason; Wasserstrom, J Andrew

    2014-01-01

    Although the development of abnormal myocardial mechanics represents a key step during the transition from hypertension to overt heart failure (HF), the underlying ultrastructural and cellular basis of abnormal myocardial mechanics remains unclear. We therefore investigated how changes in transverse (T)-tubule organization and the resulting altered intracellular Ca(2+) cycling in large cell populations underlie the development of abnormal myocardial mechanics in a model of chronic hypertension. Hearts from spontaneously hypertensive rats (SHRs; n = 72) were studied at different ages and stages of hypertensive heart disease and early HF and were compared with age-matched control (Wistar-Kyoto) rats (n = 34). Echocardiography, including tissue Doppler and speckle-tracking analysis, was performed just before euthanization, after which T-tubule organization and Ca(2+) transients were studied using confocal microscopy. In SHRs, abnormalities in myocardial mechanics occurred early in response to hypertension, before the development of overt systolic dysfunction and HF. Reduced longitudinal, circumferential, and radial strain as well as reduced tissue Doppler early diastolic tissue velocities occurred in concert with T-tubule disorganization and impaired Ca(2+) cycling, all of which preceded the development of cardiac fibrosis. The time to peak of intracellular Ca(2+) transients was slowed due to T-tubule disruption, providing a link between declining cell ultrastructure and abnormal myocardial mechanics. In conclusion, subclinical abnormalities in myocardial mechanics occur early in response to hypertension and coincide with the development of T-tubule disorganization and impaired intracellular Ca(2+) cycling. These changes occur before the development of significant cardiac fibrosis and precede the development of overt cardiac dysfunction and HF.

  5. Investigating the Development of Abnormal Subauroral Ion Drift (ASAID) and Abnormal Subauroral Polarization Stream (ASAPS) During the Magnetically Active Times of September 2003

    NASA Astrophysics Data System (ADS)

    Horvath, Ildiko; Lovell, Brian C.

    2018-02-01

    This study investigates two recently reported subauroral phenomena: the abnormal subauroral ion drift (ASAID) appearing as an inverted SAID and the shielding-E—SAID structure depicting a SAID feature on the poleward side of a small eastward or antisunward flow channel that is the shielding electric (E) field's signature. We have analyzed polar cross sections, constructed with multi-instrument Defense Meteorological Satellite Program data, for the development of these subauroral phenomena. New results show the features of abnormal subauroral polarization stream (ASAPS) and ASAID-ASAPS comprised by a narrow ASAID embedded in a wider ASAPS. We have identified undershielding, perfect shielding, and overshielding events. Our observational results demonstrate SAPS development during undershielding, the absence of subauroral flow channel during perfect shielding, and ASAID/ASAPS and shielding-E—SAID/SAPS development during overshielding. The appearance of an ASAID-ASAPS structure together with a pair of dayside-nightside eastward auroral flow channels implies the intensification of region 2 field-aligned currents via the westward traveling surge and thus the strengthening of overshielding conditions. From the observational results presented we conclude for the magnetically active time period studied that (i) the shielding E field drove the wider ASAPS flow channel, (ii) the ASAID-ASAPS structure's narrow antisunward flow channel developed due to the injections of hot ring current ions in a short-circuited system wherein the hot ring current plasma was closer to the Earth than the cold plasmaspheric plasma, and (iii) overshielding created this hot-cold plasma configuration via the development of a plasmaspheric shoulder.

  6. Inflammasome assembly in the chorioamniotic membranes during spontaneous labor at term.

    PubMed

    Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Garcia-Flores, Valeria; Leng, Yaozhu; Panaitescu, Bogdan; Miller, Derek; Abrahams, Vikki M; Hassan, Sonia S

    2017-05-01

    Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term. Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10-11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9-12 each). (i) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; (ii) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; (iii) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; (iv) ASC speck formation was detected in the choriodecidual leukocytes; and (v) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor. There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  7. Inflammasome Assembly in the Chorioamniotic Membranes during Spontaneous Labor at Term

    PubMed Central

    Gomez-Lopez, Nardhy; Romero, Roberto; Xu, Yi; Garcia-Flores, Valeria; Leng, Yaozhu; Panaitescu, Bogdan; Miller, Derek; Abrahams, Vikki M.; Hassan, Sonia S.

    2017-01-01

    Problem Inflammasome activation requires two steps: priming and assembly of the multimeric complex. The second step includes assembly of the sensor molecule and adaptor protein ASC (an apoptosis-associated speck-like protein containing a CARD), which results in ASC speck formation and the recruitment of caspase (CASP)-1. Herein, we investigated whether there is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes from women who underwent spontaneous labor at term. Method of Study Using in situ proximity ligation assays, ASC/CASP-1 complexes were determined in the chorioamniotic membranes from women who delivered at term without labor or underwent spontaneous labor at term with or without acute histologic chorioamnionitis (n=10–11 each). Also, ASC speck formation was determined by flow cytometry in the choriodecidual leukocytes isolated from women who delivered at term with or without spontaneous labor (n=9–12 each). Results 1) ASC/CASP-1 complexes were detected in the chorioamniotic membranes; 2) ASC/CASP-1 complexes were greater in the chorioamniotic membranes from women who underwent spontaneous labor at term than in those without labor; 3) ASC/CASP-1 complexes were even more abundant in the chorioamniotic membranes from women who underwent spontaneous labor at term with acute histologic chorioamnionitis than in those without this placental lesion; 4) ASC speck formation was detected in the choriodecidual leukocytes; and 5) ASC speck formation was greater in the choriodecidual leukocytes isolated from women who underwent spontaneous labor at term than in those without labor. Conclusion There is inflammasome assembly in the chorioamniotic membranes and choriodecidual leukocytes during spontaneous labor at term. PMID:28233423

  8. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...

  9. Perioperative spontaneous bilateral suprachoroidal hemorrhage

    PubMed Central

    Haridas, Anjana; Litwin, Andre S.; Coker, Timothy

    2011-01-01

    Summary Suprachoroidal hemorrhage is a rare condition, occurring most commonly in the perioperative period, although cases of unilateral spontaneous hemorrhages have been reported. We report a case of bilateral spontaneous suprachoroidal hemorrhage and discuss the potential causative factors. PMID:23362387

  10. Electrocardiographic abnormalities in amateur male marathon runners.

    PubMed

    Kaleta, Anna M; Lewicka, Ewa; Dąbrowska-Kugacka, Alicja; Lewicka-Potocka, Zuzanna; Wabich, Elżbieta; Szerszyńska, Anna; Dyda, Julia; Sobolewski, Jakub; Koenner, Jakub; Raczak, Grzegorz

    2018-06-18

    Sports activity has become extremely popular among amateurs. Electrocardiography is a useful tool in screening for cardiac pathologies in athletes; however, there is little data on electrocardiographic abnormalities in the group of amateur athletes. The aim of this study was to analyze the abnormalities in resting and exercise electrocardiograms (ECGs) in a group of amateur athletes, and try to determine whether the criteria applied for the general population or for athletes' ECGs should be implemented in this group. In 40 amateur male marathon runners, 3 consecutive 12-lead ECGs were performed: 2-3 weeks before (stage 1), just after the run (stage 2) and 2-3 weeks after the marathon (stage 3). Resting (stage 1) and exercise (stage 2) ECGs were analyzed following the refined criteria for the assessment of athlete's ECG (changes classified as training-related, borderline or training-unrelated). In resting ECGs, at least 1 abnormality was found in 92.5% of the subjects and the most common was sinus bradycardia (62.5%). In post-exercise ECGs, at least 1 abnormality was present in 77.5% of the subjects and the most common was right atrium enlargement (RAE) (42.5%). Training-related ECG variants were more frequent at rest (82.5% vs 42.5%; p = 0.0008), while borderline variants - after the run (22.5% vs 57.5%; p = 0.0004). Training-unrelated abnormalities were found in 15% and 10% of the subjects, respectively (p-value - nonsignificant), and the most common was T-wave inversion. Even if the refined criteria rather than the criteria used for normal sedentary population were applied, the vast majority of amateur runners showed at least 1 abnormality in resting ECGs, which were mainly training-related variants. However, at rest, in 15% of the subjects, pathologic training-unrelated abnormalities were found. The most frequent post-exercise abnormality was right atrial enlargement. General electrocardiographic screening in amateur athletes should be taken into consideration.

  11. Abnormal Structure–Function Relationship in Spasmodic Dysphonia

    PubMed Central

    Ludlow, Christy L.

    2012-01-01

    Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

  12. Motor Control Abnormalities in Parkinson’s Disease

    PubMed Central

    Mazzoni, Pietro; Shabbott, Britne; Cortés, Juan Camilo

    2012-01-01

    The primary manifestations of Parkinson’s disease are abnormalities of movement, including movement slowness, difficulties with gait and balance, and tremor. We know a considerable amount about the abnormalities of neuronal and muscle activity that correlate with these symptoms. Motor symptoms can also be described in terms of motor control, a level of description that explains how movement variables, such as a limb’s position and speed, are controlled and coordinated. Understanding motor symptoms as motor control abnormalities means to identify how the disease disrupts normal control processes. In the case of Parkinson’s disease, movement slowness, for example, would be explained by a disruption of the control processes that determine normal movement speed. Two long-term benefits of understanding the motor control basis of motor symptoms include the future design of neural prostheses to replace the function of damaged basal ganglia circuits, and the rational design of rehabilitation strategies. This type of understanding, however, remains limited, partly because of limitations in our knowledge of normal motor control. In this article, we review the concept of motor control and describe a few motor symptoms that illustrate the challenges in understanding such symptoms as motor control abnormalities. PMID:22675667

  13. Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: an update.

    PubMed

    Nakamura, Motonobu; Schneider, Marlon R; Schmidt-Ullrich, Ruth; Paus, Ralf

    2013-01-01

    Human hair disorders comprise a number of different types of alopecia, atrichia, hypotrichosis, distinct hair shaft disorders as well as hirsutism and hypertrichosis. Their causes vary from genodermatoses (e.g. hypotrichoses) via immunological disorders (e.g. alopecia areata, autoimmune cicatrical alopecias) to hormone-dependent abnormalities (e.g. androgenetic alopecia). A large number of spontaneous mouse mutants and genetically engineered mice develop abnormalities in hair follicle morphogenesis, cycling, and/or hair shaft formation, whose analysis has proven invaluable to define the molecular regulation of hair growth, ranging from hair follicle development, and cycling to hair shaft formation and stem cell biology. Also, the accumulating reports on hair phenotypes of mouse strains provide important pointers to better understand the molecular mechanisms underlying human hair growth disorders. Since numerous new mouse mutants with a hair phenotype have been reported since the publication of our earlier review on this matter a decade ago, we present here an updated, tabulated mini-review. The updated annotated tables list a wide selection of mouse mutants with hair growth abnormalities, classified into four categories: Mutations that affect hair follicle (1) morphogenesis, (2) cycling, (3) structure, and (4) mutations that induce extrafollicular events (for example immune system defects) resulting in secondary hair growth abnormalities. This synthesis is intended to provide a useful source of reference when studying the molecular controls of hair follicle growth and differentiation, and whenever the hair phenotypes of a newly generated mouse mutant need to be compared with existing ones. Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  14. Plasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury

    PubMed Central

    Siegel, Chad S.; Fink, Kathren L.; Strittmatter, Stephen M.

    2015-01-01

    Axons in the adult CNS fail to regenerate after injury, and therefore recovery from spinal cord injury (SCI) is limited. Although full recovery is rare, a modest degree of spontaneous recovery is observed consistently in a broad range of clinical and nonclinical situations. To define the mechanisms mediating spontaneous recovery of function after incomplete SCI, we created bilaterally complete medullary corticospinal tract lesions in adult mice, eliminating a crucial pathway for voluntary skilled movement. Anatomic and pharmacogenetic tools were used to identify the pathways driving spontaneous functional recovery in wild-type and plasticity-sensitized mice lacking Nogo receptor 1. We found that plasticity-sensitized mice recovered 50% of normal skilled locomotor function within 5 weeks of lesion. This significant, yet incomplete, spontaneous recovery was accompanied by extensive sprouting of intact rubrofugal and rubrospinal projections with the emergence of a de novo circuit between the red nucleus and the nucleus raphe magnus. Transient silencing of this rubro–raphe circuit in vivo via activation of the inhibitory DREADD (designer receptor exclusively activated by designer drugs) receptor hM4di abrogated spontaneous functional recovery. These data highlight the pivotal role of uninjured motor circuit plasticity in supporting functional recovery after trauma, and support a focus of experimental strategies on enhancing intact circuit rearrangement to promote functional recovery after SCI. PMID:25632122

  15. Disaster relief volunteerism: Evaluating cities' planning for the usage and management of spontaneous volunteers.

    PubMed

    Rivera, Jason David; Wood, Zachary David

    2016-01-01

    This exploratory study sought to observe the perceptions, usage, and planned management of spontaneous volunteers in disaster planning and response within various urban environments. The authors discuss the perceptions of spontaneous volunteerism in America, specifically the challenges of using spontaneous volunteers in disaster response activities. A content analysis of the 50 largest cities in the US Office of Emergency Management Web sites and a survey instrument administered to emergency managers in these 50 cities were used to explore various questions raised throughout the discussion of the literature. The authors found significant discrepancies between what is stated in the disaster plans of cities and what emergency managers claim is covered in their plans. Of the managers surveyed, only a handful mention spontaneous volunteers in their plans at all, and even fewer cities discuss them extensively. In addition, stated perceptions of the value of spontaneous volunteers may impact both how we plan for them and the value they provide.

  16. Electrophysiological time course and brain areas of spontaneous and intentional trait inferences

    PubMed Central

    Van Duynslaeger, Marijke; Verstraeten, Edwin

    2007-01-01

    This study measured event-related potentials during spontaneous and intentional trait inferences. Participants read sentences describing the behavior of a target person from which a strong moral trait could be inferred. The last word of each sentence determined the consistency with the trait induced during an introductory paragraph. In comparison with behaviors that were consistent with the implied trait, a P300 waveform was obtained when the behaviors were evaluative inconsistent with that trait. This dependency on behavioral consistency indicates that trait inferences were made previously while reading the preceding behaviors, irrespective of the participants’ spontaneous or intentional goals. Overall, the P300 shows considerable parallels between spontaneous and intentional inferences, indicating that the type and timing of the inconsistency process is very similar. In contrast, source localization (LORETA) of the event-related potentials suggest that spontaneous inferences show greater activation in the temporo-parietal junction compared to intentional inferences following an inconsistency. Memory measures taken after the presentation of the stimulus material involved sentence completion and trait-cued recall, and supported the occurrence of trait inferences associated with the actor. They also showed significant correlations with the neural components (i.e. P300 and its current density at the temporo-parietal junction) predominantly following spontaneous instructions, indicating that these components are valid neural indices of spontaneous inferences. PMID:18985139

  17. Different states of synaptotagmin regulate evoked versus spontaneous release

    PubMed Central

    Bai, Hua; Xue, Renhao; Bao, Huan; Zhang, Leili; Yethiraj, Arun; Cui, Qiang; Chapman, Edwin R.

    2016-01-01

    The tandem C2-domains of synaptotagmin 1 (syt) function as Ca2+-binding modules that trigger exocytosis; in the absence of Ca2+, syt inhibits spontaneous release. Here, we used proline linkers to constrain and alter the relative orientation of these C2-domains. Short poly-proline helices have a period of three, so large changes in the relative disposition of the C2-domains result from changing the length of the poly-proline linker by a single residue. The length of the linker was varied one residue at a time, revealing a periodicity of three for the ability of the linker mutants to interact with anionic phospholipids and drive evoked synaptic transmission; syt efficiently drove exocytosis when its tandem C2-domains pointed in the same direction. Analysis of spontaneous release revealed a reciprocal relationship between the activation and clamping activities of the linker mutants. Hence, different structural states of syt underlie the control of distinct forms of synaptic transmission. PMID:27001899

  18. Spontaneous and LH-induced maturation in Bufo arenarum oocytes: importance of gap junctions.

    PubMed

    Toranzo, G Sánchez; Oterino, J; Zelarayán, L; Bonilla, F; Bühler, M I

    2007-02-01

    It has been demonstrated in Bufo arenarum that fully grown oocytes are capable of meiotic resumption in the absence of a hormonal stimulus if they are deprived of their follicular envelopes. This event, called spontaneous maturation, only takes place in oocytes collected during the reproductive period, which have a metabolically mature cytoplasm. In Bufo arenarum, progesterone acts on the oocyte surface and causes modifications in the activities of important enzymes, such as a decrease in the activity of adenylate cyclase (AC) and the activation of phospholipase C (PLC). PLC activation leads to the formation of diacylglycerol (DAG) and inositol triphosphate (IP(3)), second messengers that activate protein kinase C (PKC) and cause an increase in intracellular Ca(2+). Recent data obtained from Bufo arenarum show that progesterone-induced maturation causes significant modifications in the level and composition of neutral lipids and phospholipids of whole fully grown ovarian oocytes and of enriched fractions in the plasma membrane. In amphibians, the luteinizing hormone (LH) is responsible for meiosis resumption through the induction of progesterone production by follicular cells. The aim of this work was to study the importance of gap junctions in the spontaneous and LH-induced maturation in Bufo arenarum oocytes. During the reproductive period, Bufo arenarum oocytes are capable of undergoing spontaneous maturation in a similar way to mammalian oocytes while, during the non-reproductive period, they exhibit the behaviour that is characteristic of amphibian oocytes, requiring progesterone stimulation for meiotic resumption (incapable oocytes). This different ability to mature spontaneously is coincident with differences in the amount and composition of the phospholipids in the oocyte membranes. Capable oocytes exhibit in their membranes higher quantities of phospholipids than incapable oocytes, especially of PC and PI, which are precursors of second messengers such as

  19. Video Taping and Abnormal Psychology: Dramatized Clinical Interviews.

    ERIC Educational Resources Information Center

    Lyons, Michael J.; And Others

    1984-01-01

    Students in an abnormal psychology course worked in teams to produce dramatizations of diagnostic interviews and then presented them in class. Positive and negative aspects of the activity are discussed. (RM)

  20. Urine - abnormal color

    MedlinePlus

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  1. Blockade of persistent sodium currents contributes to the riluzole-induced inhibition of spontaneous activity and oscillations in injured DRG neurons.

    PubMed

    Xie, Rou-Gang; Zheng, Da-Wei; Xing, Jun-Ling; Zhang, Xu-Jie; Song, Ying; Xie, Ya-Bin; Kuang, Fang; Dong, Hui; You, Si-Wei; Xu, Hui; Hu, San-Jue

    2011-04-25

    In addition to a fast activating and immediately inactivating inward sodium current, many types of excitable cells possess a noninactivating or slowly inactivating component: the persistent sodium current (I(NaP)). The I(NaP) is found in normal primary sensory neurons where it is mediated by tetrodotoxin-sensitive sodium channels. The dorsal root ganglion (DRG) is the gateway for ectopic impulses that originate in pathological pain signals from the periphery. However, the role of I(NaP) in DRG neurons remains unclear, particularly in neuropathic pain states. Using in vivo recordings from single medium- and large-diameter fibers isolated from the compressed DRG in Sprague-Dawley rats, we show that local application of riluzole, which blocks the I(NaP), also inhibits the spontaneous activity of A-type DRG neurons in a dose-dependent manner. Significantly, riluzole also abolished subthreshold membrane potential oscillations (SMPOs), although DRG neurons still responded to intracellular current injection with a single full-sized spike. In addition, the I(NaP) was enhanced in medium- and large-sized neurons of the compressed DRG, while bath-applied riluzole significantly inhibited the I(NaP) without affecting the transient sodium current (I(NaT)). Taken together, these results demonstrate for the first time that the I(NaP) blocker riluzole selectively inhibits I(NaP) and thereby blocks SMPOs and the ectopic spontaneous activity of injured A-type DRG neurons. This suggests that the I(NaP) of DRG neurons is a potential target for treating neuropathic pain at the peripheral level.

  2. Spontaneous mentalizing during an interactive real world task: an fMRI study.

    PubMed

    Spiers, Hugo J; Maguire, Eleanor A

    2006-01-01

    There are moments in everyday life when we need to consider the thoughts and intentions of other individuals in order to act in a socially appropriate manner. Most of this mentalizing occurs spontaneously as we go about our business in the complexity of the real world. As such, studying the neural basis of spontaneous mentalizing has been virtually impossible. Here we devised a means to achieve this by employing a unique combination of functional magnetic resonance imaging (fMRI), a detailed and interactive virtual reality simulation of a bustling familiar city, and a retrospective verbal report protocol. We were able to provide insights into the content of spontaneous mentalizing events and identify the brain regions that underlie them. We found increased activity in a number of regions, namely the right posterior superior temporal sulcus, the medial prefrontal cortex and the right temporal pole associated with spontaneous mentalizing. Furthermore, we observed the right posterior superior temporal sulcus to be consistently active during several different subtypes of mentalizing events. By contrast, medial prefrontal cortex seemed to be particularly involved in thinking about agents that were visible in the environment. Our findings show that it is possible to investigate the neural basis of mentalizing in a manner closer to its true context, the real world, opening up intriguing possibilities for making comparisons with those who have mentalizing problems.

  3. Simple platform for chronic imaging of hippocampal activity during spontaneous behaviour in an awake mouse

    PubMed Central

    Villette, Vincent; Levesque, Mathieu; Miled, Amine; Gosselin, Benoit; Topolnik, Lisa

    2017-01-01

    Chronic electrophysiological recordings of neuronal activity combined with two-photon Ca2+ imaging give access to high resolution and cellular specificity. In addition, awake drug-free experimentation is required for investigating the physiological mechanisms that operate in the brain. Here, we developed a simple head fixation platform, which allows simultaneous chronic imaging and electrophysiological recordings to be obtained from the hippocampus of awake mice. We performed quantitative analyses of spontaneous animal behaviour, the associated network states and the cellular activities in the dorsal hippocampus as well as estimated the brain stability limits to image dendritic processes and individual axonal boutons. Ca2+ imaging recordings revealed a relatively stereotyped hippocampal activity despite a high inter-animal and inter-day variability in the mouse behavior. In addition to quiet state and locomotion behavioural patterns, the platform allowed the reliable detection of walking steps and fine speed variations. The brain motion during locomotion was limited to ~1.8 μm, thus allowing for imaging of small sub-cellular structures to be performed in parallel with recordings of network and behavioural states. This simple device extends the drug-free experimentation in vivo, enabling high-stability optophysiological experiments with single-bouton resolution in the mouse awake brain. PMID:28240275

  4. Maternal immune activation and abnormal brain development across CNS disorders.

    PubMed

    Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

    2014-11-01

    Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.

  5. Abnormal small-world architecture of top–down control networks in obsessive–compulsive disorder

    PubMed Central

    Zhang, Tijiang; Wang, Jinhui; Yang, Yanchun; Wu, Qizhu; Li, Bin; Chen, Long; Yue, Qiang; Tang, Hehan; Yan, Chaogan; Lui, Su; Huang, Xiaoqi; Chan, Raymond C.K.; Zang, Yufeng; He, Yong; Gong, Qiyong

    2011-01-01

    Background Obsessive–compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD–related alterations in functional connectivity patterns in the brain’s top–down control network. Methods We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level–dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top–down control and then analyzed using graph theory-based approaches. Results Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brain’s control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. Limitations The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. Conclusion Our preliminary results suggest that the organizational patterns of

  6. Complexin Mutants Reveal Partial Segregation between Recycling Pathways That Drive Evoked and Spontaneous Neurotransmission

    PubMed Central

    Sabeva, Nadezhda; Cho, Richard W.; Vasin, Alexander; Gonzalez, Agustin; Littleton, J. Troy

    2017-01-01

    Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses. We examined synaptic vesicle recycling pathways at complexin null neuromuscular junctions, where spontaneous release is dramatically enhanced. We combined loading of the lipophilic dye FM1–43 with photoconversion, electron microscopy, and electrophysiology to monitor evoked and spontaneous recycling vesicle pools. We found that the total number of recycling vesicles was equal to those retrieved through spontaneous and evoked pools, suggesting that retrieval following fusion is partially segregated for spontaneous and evoked release. In addition, the kinetics of FM1–43 destaining and synaptic depression measured in the presence of the vesicle-refilling blocker bafilomycin indicated that spontaneous and evoked recycling pools partially intermix during the release process. Finally, FM1–43 photoconversion combined with electron microscopy analysis indicated that spontaneous recycling preferentially involves synaptic vesicles in the vicinity of AZs, whereas vesicles recycled following evoked release involve a larger intraterminal pool. Together, these results suggest that spontaneous and evoked vesicles use separable recycling pathways and then partially intermix during subsequent rounds of fusion. SIGNIFICANCE STATEMENT Neurotransmitter release involves fusion of synaptic vesicles with the plasma membrane in response to an action potential, or spontaneously in the absence of stimulation. Upon

  7. Optical antenna enhanced spontaneous emission

    PubMed Central

    Eggleston, Michael S.; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C.

    2015-01-01

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼200 THz optical frequency show a spontaneous emission intensity enhancement of 35× corresponding to a spontaneous emission rate speedup ∼115×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼2,500× spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d2. Unfortunately, at d < 10 nm, antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, Io = qω|xo|/d, feeding the antenna-enhanced spontaneous emission, where q|xo| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency. PMID:25624503

  8. Optical antenna enhanced spontaneous emission

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Eggleston, Michael S.; Messer, Kevin; Zhang, Liming

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ~200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ~115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ~2,500 × spontaneous emission speedup at d ~10 nm, proportional to 1/d 2. Unfortunately, at dmore » < 10 nm, antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Additionally, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.« less

  9. Optical antenna enhanced spontaneous emission.

    PubMed

    Eggleston, Michael S; Messer, Kevin; Zhang, Liming; Yablonovitch, Eli; Wu, Ming C

    2015-02-10

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ∼ 200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ∼ 115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ∼ 2,500 × spontaneous emission speedup at d ∼ 10 nm, proportional to 1/d(2). Unfortunately, at d < 10 nm, antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Moreover, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.

  10. Optical antenna enhanced spontaneous emission

    DOE PAGES

    Eggleston, Michael S.; Messer, Kevin; Zhang, Liming; ...

    2015-01-26

    Atoms and molecules are too small to act as efficient antennas for their own emission wavelengths. By providing an external optical antenna, the balance can be shifted; spontaneous emission could become faster than stimulated emission, which is handicapped by practically achievable pump intensities. In our experiments, InGaAsP nanorods emitting at ~200 THz optical frequency show a spontaneous emission intensity enhancement of 35 × corresponding to a spontaneous emission rate speedup ~115 ×, for antenna gap spacing, d = 40 nm. Classical antenna theory predicts ~2,500 × spontaneous emission speedup at d ~10 nm, proportional to 1/d 2. Unfortunately, at dmore » < 10 nm, antenna efficiency drops below 50%, owing to optical spreading resistance, exacerbated by the anomalous skin effect (electron surface collisions). Quantum dipole oscillations in the emitter excited state produce an optical ac equivalent circuit current, I(o) = qω|x(o)|/d, feeding the antenna-enhanced spontaneous emission, where q|x(o)| is the dipole matrix element. Despite the quantum-mechanical origin of the drive current, antenna theory makes no reference to the Purcell effect nor to local density of states models. Additionally, plasmonic effects are minor at 200 THz, producing only a small shift of antenna resonance frequency.« less

  11. Spontaneous activity responses to exercise in males and females.

    PubMed

    McLaughlin, R; Malkova, D; Nimmo, M A

    2006-09-01

    This study examines the impact of a short-term exercise programme, prescribed on the basis of current exercise recommendations, on energy balance in males and females to assess whether this type of exercise induces compensatory changes in spontaneous activity energy expenditure (SAEE) and energy intake (EI). Individuals were monitored for 16 days, 8 days of habitual physical activity (C) and 8 days when exercise was imposed (E). Total energy expenditure (TEE) was calculated from individual relationships of VO2 and VCO2 to heart rate (HR) records of HR and physical activity obtained during waking hours of the C and E periods and basal metabolic rate (BMR) measurements (Deltatrac System, Datex Instrumentation). Changes in nude body mass (BM) were estimated by using a digital scale (Sartorius AG, Gottigen, Germany). Laboratory and free-living. Eight lean females (body fat: 17.5+/-4.5%) and eight males of similar percentage body fat participated in this study. All subjects were Caucasian and aged between 20 and 25 years. During the E period, a supervised exercise session was conducted every second day, each consisting of a total net energy expenditure of 2092 kJ+BMR at 90% lactate threshold. During the E period, TEE was higher than C in males and females (exercise: 95.2+/-13.9, 78.3+/-15.9 MJ; control: 82.4+/-10.4, 68.8+/-16.7 MJ, respectively; P<0.00; P=0.02). SAEE, calculated as TEE minus the energy expended during exercise, was not significantly different between C (males: 82.4+/-4.8 MJ; females: 68.8+/-7.6 MJ) and E (males: 86.8+/-6.3 MJ; females: 70.0+/-7.2 MJ) periods in either gender. Males showed no change in BM over the C (pre-intervention: 83.4+/-7.2 kg; post-intervention: 83.1+/-6.8 kg) or E (pre-intervention: 83.4+/-6.8 kg; post-intervention: 83.4+/-6.8 kg) periods. Females' BM over the C period did not alter (pre-intervention: 63.3+/-2.8 kg; post-intervention 63.7+/-3.1 kg); however, there was a significant decrease (P<0.00) in BM over the E period (pre

  12. Comparing brain activity patterns during spontaneous exploratory and cue-instructed learning using single photon-emission computed tomography (SPECT) imaging of regional cerebral blood flow in freely behaving rats.

    PubMed

    Mannewitz, A; Bock, J; Kreitz, S; Hess, A; Goldschmidt, J; Scheich, H; Braun, Katharina

    2018-05-01

    Learning can be categorized into cue-instructed and spontaneous learning types; however, so far, there is no detailed comparative analysis of specific brain pathways involved in these learning types. The aim of this study was to compare brain activity patterns during these learning tasks using the in vivo imaging technique of single photon-emission computed tomography (SPECT) of regional cerebral blood flow (rCBF). During spontaneous exploratory learning, higher levels of rCBF compared to cue-instructed learning were observed in motor control regions, including specific subregions of the motor cortex and the striatum, as well as in regions of sensory pathways including olfactory, somatosensory, and visual modalities. In addition, elevated activity was found in limbic areas, including specific subregions of the hippocampal formation, the amygdala, and the insula. The main difference between the two learning paradigms analyzed in this study was the higher rCBF observed in prefrontal cortical regions during cue-instructed learning when compared to spontaneous learning. Higher rCBF during cue-instructed learning was also observed in the anterior insular cortex and in limbic areas, including the ectorhinal and entorhinal cortexes, subregions of the hippocampus, subnuclei of the amygdala, and the septum. Many of the rCBF changes showed hemispheric lateralization. Taken together, our study is the first to compare partly lateralized brain activity patterns during two different types of learning.

  13. Spontaneous combustion of hydrogen

    NASA Technical Reports Server (NTRS)

    Nusselt, Wilhelm; Pothmann, PH

    1923-01-01

    It is shown by the author's experiments that hydrogen which escapes to the atmosphere through openings in the system may burn spontaneously if it contains dust. Purely thermal reasoning can not account for the combustion. It seems to be rather an electrical ignition. In order to determine whether the cause of the spontaneous ignition was thermo-chemical, thermo-mechanical, or thermo-electrical, the experiments in this paper were performed.

  14. Circadian clock gene plays a key role on ovarian cycle and spontaneous abortion.

    PubMed

    Li, Ruiwen; Cheng, Shuting; Wang, Zhengrong

    2015-01-01

    Circadian locomotor output cycles protein kaput (CLOCK) plays a key role in maintaining circadian rhythms and activation of downstream elements. However, its function on human female reproductive system remains unknown. To investigate the potential role of CLOCK, CLOCK-shRNAs were transfected into mouse 129 ES cells or injected into the ovaries of adult female mice. Western blotting was utilized to analyze the protein interactions and flow cytometry was used to assess apoptosis. The expression of CLOCK peaked at the 6th week in the healthy fetuses. However, an abnormal expression of CLOCK was detected in fetuses from spontaneous miscarriage. To determine the effect of CLOCK on female fertility, a small hairpin RNA (shRNA) strategy was used to specifically knockdown the CLOCK gene expression in vitro and in vivo. Knockdown of CLOCK induced apoptosis in mouse embryonic stem (mES) cells and inhibited the proliferation in mES cells in vitro. CLOCK knockdown also led to decreased release of oocytes and smaller litter size compared with control in vivo. Collectively, theses findings indicate that CLOCK plays an important role in fertility and that the CLOCK knockdown leads to reduction in reproduction and increased miscarriage risk. © 2015 S. Karger AG, Basel.

  15. Spontaneous calcium transients in human neural progenitor cells mediated by transient receptor potential channels.

    PubMed

    Morgan, Peter J; Hübner, Rayk; Rolfs, Arndt; Frech, Moritz J

    2013-09-15

    Calcium signals affect many developmental processes, including proliferation, migration, survival, and apoptosis, processes that are of particular importance in stem cells intended for cell replacement therapies. The mechanisms underlying Ca(2+) signals, therefore, have a role in determining how stem cells respond to their environment, and how these responses might be controlled in vitro. In this study, we examined the spontaneous Ca(2+) activity in human neural progenitor cells during proliferation and differentiation. Pharmacological characterization indicates that in proliferating cells, most activity is the result of transient receptor potential (TRP) channels that are sensitive to Gd(3+) and La(3+), with the more subtype selective antagonist Ruthenium red also reducing activity, suggesting the involvement of transient receptor potential vanilloid (TRPV) channels. In differentiating cells, Gd(3+) and La(3+)-sensitive TRP channels also appear to underlie the spontaneous activity; however, no sub-type-specific antagonists had any effect. Protein levels of TRPV2 and TRPV3 decreased in differentiated cells, which is demonstrated by western blot. Thus, it appears that TRP channels represent the main route of Ca(2+) entry in human neural progenitor cells (hNPCs), but the responsible channel types are subject to substitution under differentiating conditions. The level of spontaneous activity could be increased and decreased by lowering and raising the extracellular K(+) concentration. Proliferating cells in low K(+) slowed the cell cycle, with a disproportionate increased percentage of cells in G1 phase and a reduction in S phase. Taken together, these results suggest a link between external K(+) concentration, spontaneous Ca(2+) transients, and cell cycle distribution, which is able to influence the fate of stem and progenitor cells.

  16. Abnormal proactive and reactive cognitive control during conflict processing in major depression.

    PubMed

    Vanderhasselt, Marie-Anne; De Raedt, Rudi; De Paepe, Annick; Aarts, Kristien; Otte, Georges; Van Dorpe, Jan; Pourtois, Gilles

    2014-02-01

    According to the Dual Mechanisms of Control framework, cognitive control consists of two complementary components: proactive control refers to anticipatory maintenance of goal-relevant information, whereas reactive control acts as a correction mechanism that is activated when a conflict occurs. Possibly, the well-known diminished inhibitory control in response to negative stimuli in Major Depressive Disorder (MDD) patients stems from a breakdown in proactive control, and/or anomalies in reactive cognitive control. In our study, MDD patients specifically showed increased response latencies when actively inhibiting a dominant response to a sad compared with a happy face. This condition was associated with a longer duration of a dominant ERP topography (800-900 ms poststimulus onset) and a stronger activity in the bilateral dorsal anterior cingulate cortex, reflecting abnormal reactive control when inhibiting attention to a negative stimulus. Moreover, MDD patients showed abnormalities in proactive cognitive control when preparing for the upcoming imperative stimulus (abnormal modulation of the contingent negative variation component), accompanied by more activity in brain regions belonging to the default mode network. All together, deficits to inhibit attention to negative information in MDD might originate from an abnormal use of both proactive resources and reactive control processes. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  17. Biochemical abnormalities in Pearson syndrome.

    PubMed

    Crippa, Beatrice Letizia; Leon, Eyby; Calhoun, Amy; Lowichik, Amy; Pasquali, Marzia; Longo, Nicola

    2015-03-01

    Pearson marrow-pancreas syndrome is a multisystem mitochondrial disorder characterized by bone marrow failure and pancreatic insufficiency. Children who survive the severe bone marrow dysfunction in childhood develop Kearns-Sayre syndrome later in life. Here we report on four new cases with this condition and define their biochemical abnormalities. Three out of four patients presented with failure to thrive, with most of them having normal development and head size. All patients had evidence of bone marrow involvement that spontaneously improved in three out of four patients. Unique findings in our patients were acute pancreatitis (one out of four), renal Fanconi syndrome (present in all patients, but symptomatic only in one), and an unusual organic aciduria with 3-hydroxyisobutyric aciduria in one patient. Biochemical analysis indicated low levels of plasma citrulline and arginine, despite low-normal ammonia levels. Regression analysis indicated a significant correlation between each intermediate of the urea cycle and the next, except between ornithine and citrulline. This suggested that the reaction catalyzed by ornithine transcarbamylase (that converts ornithine to citrulline) might not be very efficient in patients with Pearson syndrome. In view of low-normal ammonia levels, we hypothesize that ammonia and carbamylphosphate could be diverted from the urea cycle to the synthesis of nucleotides in patients with Pearson syndrome and possibly other mitochondrial disorders. © 2015 Wiley Periodicals, Inc.

  18. Abnormal Superior Temporal Connectivity During Fear Perception in Schizophrenia

    PubMed Central

    Leitman, David I.; Loughead, James; Wolf, Daniel H.; Ruparel, Kosha; Kohler, Christian G.; Elliott, Mark A.; Bilker, Warren B.; Gur, Raquel E.; Gur, Ruben C.

    2008-01-01

    Patients with schizophrenia have difficulty in decoding facial affect. A study using event–related functional neuroimaging indicated that errors in fear detection in schizophrenia are associated with paradoxically higher activation in the amygdala and an associated network implicated in threat detection. Furthermore, this exaggerated activation to fearful faces correlated with severity of flat affect. These findings suggest that abnormal threat detection processing may reflect disruptions between nodes that comprise the affective appraisal circuit. Here we examined connectivity within this network by determining the pattern of intercorrelations among brain regions (regions of interest) significantly activated during fear identification in both healthy controls and patients using a novel procedure CORANOVA. This analysis tests differences in the interregional correlation strength between schizophrenia and healthy controls. Healthy subjects' task activation was principally characterized by robust correlations between medial structures like thalamus (THA) and amygdala (AMY) and middle frontal (MF), inferior frontal (IF), and prefrontal cortical (PFC) regions. In contrast, schizophrenia patients displayed no significant correlations between the medial regions and either MF or IF. Further, patients had significantly higher correlations between occipital lingual gyrus and superior temporal gyrus than healthy subjects. These between-group connectivity differences suggest that schizophrenia threat detection impairment may stem from abnormal stimulus integration. Such abnormal integration may disrupt the evaluation of threat within fronto-cortical regions. PMID:18550592

  19. Clinical observation of lymphocyte active immunotherapy in 380 patients with unexplained recurrent spontaneous abortion.

    PubMed

    Chen, Jian-Ling; Yang, Jian-Ming; Huang, Ya-Zhe; Li, Ying

    2016-11-01

    This study aims to investigate the clinical curative effect of lymphocyte active immunotherapy (LAI) on unexplained recurrent spontaneous abortion (RSA). A total of 749 RSA patients who received medical service in our hospital from October 2009 to June 2013 were enrolled into this study. These patients were randomly divided into two groups: LAI group (treatment group) and routine progesterone for maintenance tocolysis group (control group). A comparative analysis on the pregnancy outcomes in these two groups was conducted. Abortion rate was significantly lower in the LAI group than in the control group (P<0.05). Furthermore, pregnancy success rates were 89.7% and 32.2% in patients who received LAI and routine progesterone for maintenance tocolysis, respectively, and the difference was statistically significant (P<0.05). Our analysis suggested that LAI can treat RSA effectively and has an excellent clinical effect. Furthermore, the detection of blocking antibodies showed a positive prediction on pregnancy outcome. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Extraction of ECG signal with adaptive filter for hearth abnormalities detection

    NASA Astrophysics Data System (ADS)

    Turnip, Mardi; Saragih, Rijois. I. E.; Dharma, Abdi; Esti Kusumandari, Dwi; Turnip, Arjon; Sitanggang, Delima; Aisyah, Siti

    2018-04-01

    This paper demonstrates an adaptive filter method for extraction ofelectrocardiogram (ECG) feature in hearth abnormalities detection. In particular, electrocardiogram (ECG) is a recording of the heart's electrical activity by capturing a tracingof cardiac electrical impulse as it moves from the atrium to the ventricles. The applied algorithm is to evaluate and analyze ECG signals for abnormalities detection based on P, Q, R and S peaks. In the first phase, the real-time ECG data is acquired and pre-processed. In the second phase, the procured ECG signal is subjected to feature extraction process. The extracted features detect abnormal peaks present in the waveform. Thus the normal and abnormal ECG signal could be differentiated based on the features extracted.

  1. Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity.

    PubMed

    Telinius, Niklas; Drewsen, Nanna; Pilegaard, Hans; Kold-Petersen, Henrik; de Leval, Marc; Aalkjaer, Christian; Hjortdal, Vibeke; Boedtkjer, Donna Briggs

    2010-09-01

    The current study characterizes the mechanical properties of the human thoracic duct and demonstrates a role for adrenoceptors, thromboxane, and endothelin receptors in human lymph vessel function. With ethical permission and informed consent, portions of the thoracic duct (2-5 cm) were resected and retrieved at T(7)-T(9) during esophageal and cardia cancer surgery. Ring segments (2 mm long) were mounted in a myograph for isometric tension (N/m) measurement. The diameter-tension relationship was established using ducts from 10 individuals. Peak active tension of 6.24 +/- 0.75 N/m was observed with a corresponding passive tension of 3.11 +/- 0.67 N/m and average internal diameter of 2.21 mm. The equivalent active and passive transmural pressures by LaPlace's law were 47.3 +/- 4.7 and 20.6 +/- 3.2 mmHg, respectively. Subsequently, pharmacology was performed on rings from 15 ducts that were normalized by stretching them until an equivalent pressure of 21 mmHg was calculable from the wall tension. At low concentrations, norepinephrine, endothelin-1, and the thromboxane-A(2) analog U-46619 evoked phasic contractions (analogous to lymphatic pumping), whereas at higher contractions they induced tonic activity (maximum tension values of 4.46 +/- 0.63, 5.90 +/- 1.4, and 6.78 +/- 1.4 N/m, respectively). Spontaneous activity was observed in 44% of ducts while 51% of all the segments produced phasic contractions after agonist application. Acetylcholine and bradykinin relaxed norepinephrine preconstrictions by approximately 20% and approximately 40%, respectively. These results demonstrate that the human thoracic duct can develop wall tensions that permit contractility to be maintained across a wide range of transmural pressures and that isolated ducts contract in response to important vasoactive agents.

  2. Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder.

    PubMed

    Murphy, Clodagh M; Christakou, Anastasia; Giampietro, Vincent; Brammer, Michael; Daly, Eileen M; Ecker, Christine; Johnston, Patrick; Spain, Debbie; Robertson, Dene M; Murphy, Declan G; Rubia, Katya

    2017-11-01

    People with autism spectrum disorder (ASD) have poor decision-making and temporal foresight. This may adversely impact on their everyday life, mental health, and productivity. However, the neural substrates underlying poor choice behavior in people with ASD, or its' neurofunctional development from childhood to adulthood, are unknown. Despite evidence of atypical structural brain development in ASD, investigation of functional brain maturation in people with ASD is lacking. This cross-sectional developmental fMRI study investigated the neural substrates underlying performance on a temporal discounting (TD) task in 38 healthy (11-35 years old) male adolescents and adults with ASD and 40 age, sex, and IQ-matched typically developing healthy controls. Most importantly, we assessed group differences in the neurofunctional maturation of TD across childhood and adulthood. Males with ASD had significantly poorer task performance and significantly lower brain activation in typical regions that mediate TD for delayed choices, in predominantly right hemispheric regions of ventrolateral/dorsolateral prefrontal cortices, ventromedial prefrontal cortex, striatolimbic regions, and cerebellum. Importantly, differential activation in ventromedial frontal cortex and cerebellum was associated with abnormal functional brain maturation; controls, in contrast to people with ASD, showed progressively increasing activation with increasing age in these regions; which furthermore was associated with performance measures and clinical ASD measures (stereotyped/restricted interests). Findings provide first cross-sectional evidence that reduced activation of TD mediating brain regions in people with ASD during TD is associated with abnormal functional brain development in these regions between childhood and adulthood, and this is related to poor task performance and clinical measures of ASD. Hum Brain Mapp 38:5343-5355, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  3. Toward a complex system understanding of bipolar disorder: A chaotic model of abnormal circadian activity rhythms in euthymic bipolar disorder.

    PubMed

    Hadaeghi, Fatemeh; Hashemi Golpayegani, Mohammad Reza; Jafari, Sajad; Murray, Greg

    2016-08-01

    In the absence of a comprehensive neural model to explain the underlying mechanisms of disturbed circadian function in bipolar disorder, mathematical modeling is a helpful tool. Here, circadian activity as a response to exogenous daily cycles is proposed to be the product of interactions between neuronal networks in cortical (cognitive processing) and subcortical (pacemaker) areas of the brain. To investigate the dynamical aspects of the link between disturbed circadian activity rhythms and abnormalities of neurotransmitter functioning in frontal areas of the brain, we developed a novel mathematical model of a chaotic system which represents fluctuations in circadian activity in bipolar disorder as changes in the model's parameters. A novel map-based chaotic system was developed to capture disturbances in circadian activity across the two extreme mood states of bipolar disorder. The model uses chaos theory to characterize interplay between neurotransmitter functions and rhythm generation; it aims to illuminate key activity phenomenology in bipolar disorder, including prolonged sleep intervals, decreased total activity and attenuated amplitude of the diurnal activity rhythm. To test our new cortical-circadian mathematical model of bipolar disorder, we utilized previously collected locomotor activity data recorded from normal subjects and bipolar patients by wrist-worn actigraphs. All control parameters in the proposed model have an important role in replicating the different aspects of circadian activity rhythm generation in the brain. The model can successfully replicate deviations in sleep/wake time intervals corresponding to manic and depressive episodes of bipolar disorder, in which one of the excitatory or inhibitory pathways is abnormally dominant. Although neuroimaging research has strongly implicated a reciprocal interaction between cortical and subcortical regions as pathogenic in bipolar disorder, this is the first model to mathematically represent this

  4. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  5. Differential neurotoxic effects of in utero and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice.

    PubMed

    Haijima, Asahi; Lesmana, Ronny; Shimokawa, Noriaki; Amano, Izuki; Takatsuru, Yusuke; Koibuchi, Noriyuki

    2017-01-01

    We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development.

  6. Spontaneous pneumothorax in diffuse cystic lung diseases.

    PubMed

    Cooley, Joseph; Lee, Yun Chor Gary; Gupta, Nishant

    2017-07-01

    Diffuse cystic lung diseases (DCLDs) are a heterogeneous group of disorders with varying pathophysiologic mechanisms that are characterized by the presence of air-filled lung cysts. These cysts are prone to rupture, leading to the development of recurrent spontaneous pneumothoraces. In this article, we review the epidemiology, clinical features, and management DCLD-associated spontaneous pneumothorax, with a focus on lymphangioleiomyomatosis, Birt-Hogg-Dubé syndrome, and pulmonary Langerhans cell histiocytosis. DCLDs are responsible for approximately 10% of apparent primary spontaneous pneumothoraces. Computed tomography screening for DCLDs (Birt-Hogg-Dubé syndrome, lymphangioleiomyomatosis, and pulmonary Langerhans cell histiocytosis) following the first spontaneous pneumothorax has recently been shown to be cost-effective and can help facilitate early diagnosis of the underlying disorders. Patients with DCLD-associated spontaneous pneumothorax have a very high rate of recurrence, and thus pleurodesis should be considered following the first episode of spontaneous pneumothorax in these patients, rather than waiting for a recurrent episode. Prior pleurodesis is not a contraindication to future lung transplant. Although DCLDs are uncommon, spontaneous pneumothorax is often the sentinel event that provides an opportunity for diagnosis. By understanding the burden and implications of pneumothoraces in DCLDs, clinicians can facilitate early diagnosis and appropriate management of the underlying disorders.

  7. [Botulinum toxin type A does not affect spontaneous discharge but blocks sympathetic-sensory coupling in chronically compressed rat dorsal root ganglion neurons].

    PubMed

    Yang, Hong-jun; Peng, Kai-run; Hu, San-jue; Duan, Jian-hong

    2007-11-01

    To study the effect of botulinum toxin type A (BTXA) on spontaneous discharge and sympathetic- sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats. In chronically compressed rat DRG, spontaneous activities of the single fibers from DRG neurons were recorded and their changes observed after BTAX application on the damaged DGR. Sympathetic modulation of the spontaneous discharge from the compressed DRG neurons was observed by electric stimulation of the lumbar sympathetic trunk, and the changes in this effect were evaluated after intravenous BTXA injection in the rats. Active spontaneous discharges were recorded in the injured DRG neurons, and 47 injured DRG neurons responded to Ca2+-free artificial cerebrospinal fluid but not to BTXA treatment. Sixty-four percent of the neurons in the injured DRG responded to sympathetic stimulation, and this response was blocked by intravenously injection of BTXA. BTXA does not affect spontaneous activities of injured DRG neurons, but blocks sympathetic-sensory coupling in these neurons.

  8. Effects of substance P on spontaneous contraction in the flexure region of the guinea pig colon.

    PubMed

    Chowdhury, J U; Nahar, N S

    2007-01-01

    Effects of Substance P on spontaneous contractions of the circular muscle of the flexure region of guinea pig colon were studied by mechanical tension recording. Substance P (3 nM-10 nM) produced tonic contraction associated with phasic activities but the contraction was found stronger at higher concentration. Verapamil (3 microM), a voltage dependent L-type Ca(2+) channel blocker completely blocked the spontaneous activities and also Substance P induced contraction. These results suggest that Substance P produce contraction by Ca(2+) influx and the Ca(2+) influx occurs by activating verapamil sensitive Ca(2+) channel.

  9. Beyond blow-up in excitatory integrate and fire neuronal networks: Refractory period and spontaneous activity.

    PubMed

    Cáceres, María J; Perthame, Benoît

    2014-06-07

    The Network Noisy Leaky Integrate and Fire equation is among the simplest model allowing for a self-consistent description of neural networks and gives a rule to determine the probability to find a neuron at the potential v. However, its mathematical structure is still poorly understood and, concerning its solutions, very few results are available. In the midst of them, a recent result shows blow-up in finite time for fully excitatory networks. The intuitive explanation is that each firing neuron induces a discharge of the others; thus increases the activity and consequently the discharge rate of the full network. In order to better understand the details of the phenomena and show that the equation is more complex and fruitful than expected, we analyze further the model. We extend the finite time blow-up result to the case when neurons, after firing, enter a refractory state for a given period of time. We also show that spontaneous activity may occur when, additionally, randomness is included on the firing potential VF in regimes where blow-up occurs for a fixed value of VF. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Risk factors for postpartum ovarian cysts and their spontaneous recovery or persistence in lactating dairy cows.

    PubMed

    López-Gatius, F; Santolaria, P; Yániz, J; Fenech, M; López-Béjar, M

    2002-11-01

    Cystic ovarian disease is a major cause of reproductive failure and economic loss for the dairy industry. Many cysts that develop during the early postpartum period regress spontaneously. However, it is difficult to decide at what point it would be more cost effective to treat ovarian cysts than to wait for spontaneous recovery. The objective of this study was to analyze risk factors for the development of the ovarian cystic condition during early and late postpartum, and for its persistence or recovery during the pre-service period in lactating dairy cows. Using multiple logistic regression, we analyzed data derived from 873 lactating dairy cows from a single herd. An ovarian cyst was diagnosed if it was possible to observe a single follicular structure with an antrum diameter > or = 25 mm in the absence of a corpus luteum in three sonograms performed at 7-day intervals. The cystic condition was denoted as early if the cyst was diagnosed 43-49 days postpartum, and late if detected 57-63-day postpartum. Spontaneous cyst regression before 60-day postpartum was regarded as early cystic recovery. For the early cystic group, there were no significant effects of lactation number, body condition score on prepartum Day 60, at parturition or on postpartum Day 30, or of body condition loss from parturition to 30-day postpartum. Cows calving in summer were 2.6 times more likely to develop ovarian cysts than those giving birth in winter. The risk of having a cyst was 1.9 times higher in cows with an abnormal puerperium. A 1-kg increase in milk yield raised the risk of cysts by a factor of 1.05. A 1-unit increase in body condition score (scale from 1 to 5) from prepartum Day 60 to parturition increased the risk of cyst development 8.4 times. Milk production and lactation number were negatively correlated with spontaneous early cyst recovery. A 1-kg decrease in milk production increased the probability of cyst recovery by a factor of 1.06, and a 1-unit drop in lactation number

  11. An M1-like Macrophage Polarization in Decidual Tissue during Spontaneous Preterm Labor That Is Attenuated by Rosiglitazone Treatment.

    PubMed

    Xu, Yi; Romero, Roberto; Miller, Derek; Kadam, Leena; Mial, Tara N; Plazyo, Olesya; Garcia-Flores, Valeria; Hassan, Sonia S; Xu, Zhonghui; Tarca, Adi L; Drewlo, Sascha; Gomez-Lopez, Nardhy

    2016-03-15

    Decidual macrophages are implicated in the local inflammatory response that accompanies spontaneous preterm labor/birth; however, their role is poorly understood. We hypothesized that decidual macrophages undergo a proinflammatory (M1) polarization during spontaneous preterm labor and that PPARγ activation via rosiglitazone (RSG) would attenuate the macrophage-mediated inflammatory response, preventing preterm birth. In this study, we show that: 1) decidual macrophages undergo an M1-like polarization during spontaneous term and preterm labor; 2) anti-inflammatory (M2)-like macrophages are more abundant than M1-like macrophages in decidual tissue; 3) decidual M2-like macrophages are reduced in preterm pregnancies compared with term pregnancies, regardless of the presence of labor; 4) decidual macrophages express high levels of TNF and IL-12 but low levels of peroxisome proliferator-activated receptor γ (PPARγ) during spontaneous preterm labor; 5) decidual macrophages from women who underwent spontaneous preterm labor display plasticity by M1↔M2 polarization in vitro; 6) incubation with RSG reduces the expression of TNF and IL-12 in decidual macrophages from women who underwent spontaneous preterm labor; and 7) treatment with RSG reduces the rate of LPS-induced preterm birth and improves neonatal outcomes by reducing the systemic proinflammatory response and downregulating mRNA and protein expression of NF-κB, TNF, and IL-10 in decidual and myometrial macrophages in C57BL/6J mice. In summary, we demonstrated that decidual M1-like macrophages are associated with spontaneous preterm labor and that PPARγ activation via RSG can attenuate the macrophage-mediated proinflammatory response, preventing preterm birth and improving neonatal outcomes. These findings suggest that the PPARγ pathway is a new molecular target for future preventative strategies for spontaneous preterm labor/birth. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Transgenic overexpression of p23 induces spontaneous hydronephrosis in mice

    PubMed Central

    Lee, Jaehoon; Kim, Hye Jin; Moon, Jung Ah; Sung, Young Hoon; Baek, In-Jeoung; Roh, Jae-il; Ha, Na Young; Kim, Seung-Yeon; Bahk, Young Yil; Lee, Jong Eun; Yoo, Tae Hyun; Lee, Han-Woong

    2011-01-01

    p23 is a cochaperone of heat shock protein 90 and also interacts functionally with numerous steroid receptors and kinases. However, the in vivo roles of p23 remain unclear. To explore its in vivo function, we generated the transgenic (TG) mice ubiquitously overexpressing p23. The p23 TG mice spontaneously developed kidney abnormalities closely resembling human hydronephrosis. Consistently, kidney functions deteriorate significantly in the p23 TG mice compared to their wild-type (WT) littermates. Furthermore, the expression of target genes for aryl hydrocarbon receptor (AhR), such as cytochrome P450, family 1, subfamily A, polypeptide 1 (Cyp1A1) and cytochrome P450, family 1, subfamily B, polypeptide 1 (Cyp1B1), were induced in the kidneys of the p23 TG mice. These results indicate that the overexpression of p23 contributes to the development of hydronephrosis through the upregulation of the AhR pathway in vivo. PMID:21323770

  13. Mycophenolate mofetil prevents cerebrovascular injury in stroke-prone spontaneously hypertensive rats.

    PubMed

    Dhande, Isha S; Zhu, Yaming; Braun, Michael C; Hicks, M John; Wenderfer, Scott E; Doris, Peter A

    2017-03-01

    Stroke-prone spontaneously hypertensive rats (SHR-A3) develop strokes and progressive kidney disease as a result of naturally occurring genetic variations. We recently identified genetic variants in immune signaling pathways that contribute to end-organ injury. The present study was designed to test the hypothesis that a dysregulated immune response promotes stroke susceptibility. We salt-loaded 20 wk old male SHR-A3 rats and treated them with the immunosuppressant mycophenolate mofetil (MMF, 25 mg/kg/day po) ( n = 8) or vehicle (saline) ( n = 9) for 8 wk. Blood pressure (BP) was measured weekly by telemetry. Compared with vehicle-treated controls, MMF-treated SHR-A3 rats had improved survival and lower neurological deficit scores (1.44 vs. 0.125; P < 0.02). Gross morphology of the brain revealed cerebral edema in 8 of 9, and microbleeds and hemorrhages in 5 of 9 vehicle-treated rats. These lesions were absent in MMF-treated rats. Brain CD68 expression, indicating macrophage/microglial activation, was upregulated in vehicle-treated rats with microbleeds and hemorrhages but was undetectable in the brains of MMF-treated rats. MMF also prevented renal injury in SHR-A3 rats, evidenced by reduced proteinuria (albumin:creatinine) from 7.52 to 1.05 mg/mg ( P < 0.03) and lower tubulointerstitial injury scores (2.46 vs. 1.43; P < 0.01). Salt loading resulted in a progressive increase in BP, which was blunted in rats receiving MMF. Our findings provide evidence that abnormal immune activation predisposes to cerebrovascular and renal injury in stroke-prone SHR-A3 rats. Copyright © 2017 the American Physiological Society.

  14. Spontaneous remission of IgA nephropathy associated with resolution of hepatitis A.

    PubMed

    Han, Seung Hyeok; Kang, Ea Wha; Kie, Jeong Hae; Yoo, Tae Hyun; Choi, Kyu Hun; Han, Dae-Suk; Kang, Shin-Wook

    2010-12-01

    Although most cases of immunoglobulin A (IgA) nephropathy are idiopathic, several diseases are associated with IgA nephropathy. Of these, chronic liver disease resulting from hepatitis B or C virus infection has been reported as a secondary cause of IgA nephropathy. Recently, hepatitis A virus (HAV)-associated kidney disease has received attention because acute kidney injury can occur as a complication of HAV infection, generally caused by acute tubular necrosis or interstitial nephritis. However, unlike IgA nephropathy related to hepatitis B or C, HAV-associated IgA nephropathy is extremely rare and long-term outcomes have not been reported yet. We describe a case of spontaneous remission of IgA nephropathy associated with serologically documented HAV infection. The patient presented with microhematuria and moderate proteinuria, but acute kidney injury did not occur during active hepatic injury. Kidney biopsy specimens clearly showed mesangial IgA deposits with intact tubules and interstitium. Serum liver enzyme levels returned to reference values 1 month after the onset of acute hepatitis, but urinary protein excretion remained increased. Approximately 1 year later, urinary abnormalities were resolved and a second biopsy showed no mesangial IgA deposits. These findings suggest that IgA nephropathy can transiently accompany HAV infection, but may not progress to chronic glomerulonephritis after recovery from HAV. Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  15. Abnormalities of Object Visual Processing in Body Dysmorphic Disorder

    PubMed Central

    Feusner, Jamie D.; Hembacher, Emily; Moller, Hayley; Moody, Teena D.

    2013-01-01

    Background Individuals with body dysmorphic disorder may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with body dysmorphic disorder have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. Methods Fourteen medication-free participants with DSM-IV body dysmorphic disorder and 14 healthy controls participated. We performed functional magnetic resonance imaging while participants matched photographs of houses that were unaltered, contained only high spatial frequency (high detail) information, or only low spatial frequency (low detail) information. The primary outcome was group differences in blood oxygen level-dependent signal changes. Results The body dysmorphic disorder group showed lesser activity in the parahippocampal gyrus, lingual gyrus, and precuneus for low spatial frequency images. There were greater activations in medial prefrontal regions for high spatial frequency images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lesser activity in dorsal occipital cortex and ventrolateral prefrontal cortex for normal and high spatial frequency images. Conclusions Individuals with body dysmorphic disorder have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details is consistent with a model of imbalances in global vs. local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms. PMID:21557897

  16. Spontaneous splenic rupture in infectious mononucleosis.

    PubMed

    Rothwell, S; McAuley, D

    2001-09-01

    Spontaneous splenic rupture is a rare but life-threatening complication of infectious mononucleosis. Abdominal pain and tachycardia are unusual in uncomplicated infectious mononucleosis and should alert a doctor to the possibility of spontaneous splenic rupture.

  17. A new engineering approach to reveal correlation of physiological change and spontaneous expression from video images

    NASA Astrophysics Data System (ADS)

    Yang, Fenglei; Hu, Sijung; Ma, Xiaoyun; Hassan, Harnani; Wei, Dongqing

    2015-03-01

    Spontaneous expression is associated with physiological states, i.e., heart rate, respiration, oxygen saturation (SpO2%), and heart rate variability (HRV). There have yet not sufficient efforts to explore correlation of physiological change and spontaneous expression. This study aims to study how spontaneous expression is associated with physiological changes with an approved protocol or through the videos provided from Denver Intensity of Spontaneous Facial Action Database. Not like a posed expression, motion artefact in spontaneous expression is one of evitable challenges to be overcome in the study. To obtain a physiological signs from a region of interest (ROI), a new engineering approach is being developed with an artefact-reduction method consolidated 3D active appearance model (AAM) based track, affine transformation based alignment with opto-physiological mode based imaging photoplethysmography. Also, a statistical association spaces is being used to interpret correlation of spontaneous expressions and physiological states including their probability densities by means of Gaussian Mixture Model. The present work is revealing a new avenue of study associations of spontaneous expressions and physiological states with its prospect of applications on physiological and psychological assessment.

  18. Changes in Problem-Solving Capacity and Association With Spontaneous Brain Activity After a Single Electroconvulsive Treatment in Major Depressive Disorder.

    PubMed

    Du, Lian; Qiu, Haitang; Liu, Haixia; Zhao, Wenjing; Tang, Yong; Fu, Yixiao; Li, Xirong; Qiu, Tian; Hu, Hua; Meng, Huaqing; Luo, Qinghua

    2016-03-01

    Modified electroconvulsive therapy (MECT) has been regarded as the most effective antidepressant therapy, despite its cognitive side effects. However, how MECT influences problem-solving capacity in major depressive disorder (MDD), as well as its underlying neurobiological mechanisms, remains unclear. The present study aimed to assess alterations in problem-solving capacity after MECT and to explore spontaneous brain activity using amplitudes of low-frequency fluctuations (ALFF)/fractional ALFF. Thirteen first-episode, treatment-naive MDD patients treated by MECT were recruited. We collected resting-state functional magnetic resonance imaging, and we evaluated their Modified Card Sorting Test performance before and after single-session MECT. Another 11 MDD patients without MECT were also recruited and interviewed with Modified Card Sorting Test twice as a control group. After a single MECT, MDD patients showed significantly decreased ALFF in the right cerebellar posterior lobe. Compared to the control group, perseverative errors significantly decreased after MECT, controlling for practice effects. Some cognitive functional changes significantly correlated to changed ALFF in several brain regions, including Brodmann areas BA9, BA19, BA 21, and BA48, right thalamus, left cerebellum, and right postcentral gyrus. The MECT could improve problem-solving capacity, even after controlling for practice effects, and it could induce changes in spontaneous brain activity. These changes in cognitive functioning might result from changes in the cerebral functions of some regions, including frontal cortex, a key region for problem-solving capacity.

  19. The pronociceptive dorsal reticular nucleus contains mostly tonic neurons and shows a high prevalence of spontaneous activity in block preparation.

    PubMed

    Sousa, Mafalda; Szucs, Peter; Lima, Deolinda; Aguiar, Paulo

    2014-04-01

    Despite the importance and significant clinical impact of understanding information processing in the nociceptive system, the functional properties of neurons in many parts of this system are still unknown. In this work we performed whole cell patch-clamp recording in rat brain stem blocks to characterize the electrophysiological properties of neurons in the dorsal reticular nucleus (DRt), a region known to be involved in pronociceptive modulation. We also compared properties of DRt neurons with those in the adjacent parvicellular reticular nucleus and in neighboring regions outside the reticular formation. We found that neurons in the DRt and parvicellular reticular nucleus had similar electrophysiological properties and exhibited mostly toniclike firing patterns, whereas neurons outside the reticular formation showed a larger diversity of firing patterns. Interestingly, more than one-half of the neurons also showed spontaneous activity. While the general view of the reticular formation, being a loosely associated mesh of groups of neurons with diverse function, and earlier reports suggests more electrophysiological heterogeneity, we showed that this is indeed not the case. Our results indicate that functional difference of neurons in the reticular formation may mostly be determined by their connectivity profiles and not by their intrinsic electrophysiological properties. The dominance of tonic neurons in the DRt supports previous conclusions that these neurons encode stimulus intensity through their firing frequency, while the high prevalence of spontaneous activity most likely shapes nociceptive modulation by this brain stem region.

  20. Endogenous Melanocortin System Activity Contributes to the Elevated Arterial Pressure in Spontaneously Hypertensive Rats

    PubMed Central

    da Silva, Alexandre A.; do Carmo, Jussara M.; Kanyicska, Bela; Dubinion, John; Brandon, Elizabeth; Hall, John E.

    2009-01-01

    Previous studies suggest that activation of the CNS melanocortin system reduces appetite while increasing sympathetic activity and arterial pressure. The present study tested whether endogenous activity of the CNS melanocortin 3/4 receptors (MC3/4-R) contributes to elevated arterial pressure in the spontaneously hypertensive rat (SHR), a model of hypertension with increased sympathetic activity. A cannula was placed in the lateral ventricle of male SHR and Wistar (WKY) rats for chronic intracerebroventricular (ICV) infusions (0.5 μL/h). Mean arterial pressure (MAP) and heart rate (HR) were recorded 24 hour/d using telemetry. After 5-day control period, rats were infused with MC3/4-R antagonist (SHU-9119, 1 nmol/h-ICV) for 12 days, followed by 5-day posttreatment period. MC3/4-R antagonism increased food intake in SHR by 90% and in WKY by 125%, resulting in marked weight gain, insulin resistance, and hyperleptinemia in SHR and WKY. Despite weight gain, MC3/4-R antagonism reduced HR in SHR and WKY (≈40 bpm), while lowering MAP to a greater extent in SHR (−22±4 mm Hg) than WKY (−4±3 mm Hg). SHU9119 treatment failed to cause further reductions in MAP during chronic adrenergic blockade with propranolol and terazosin. These results suggest that endogenous activity of the CNS melanocortin system contributes to the maintenance of adrenergic tone and elevated arterial pressure in SHR even though mRNA levels for POMC and MC4R in the mediobasal hypothalamus were not increased compared to WKY. These results also support the hypothesis that weight gain does not raise arterial pressure in the absence of a functional MC3/4-R. PMID:18285617