Sample records for abnormal thalamocortical dynamics

  1. Bilateral Thalamocortical Abnormalities in Focal Cortical Dysplasia.

    PubMed

    Rezayev, Arthur; Feldman, Henry A; Levman, Jacob; Takahashi, Emi

    2018-05-05

    Focal cortical dysplasia (FCD), a congenital malformation of the neocortex and one of the most common causes of medication resistant epilepsy in pediatric populations, can be studied noninvasively by diffusion tensor imaging (DTI). The present study aimed to quantify changes in the thalamus and thalamocortical pathways with respect to fractional anisotropy (FA), apparent diffusion coefficient (ADC), volume, and other common measures. The study quantified data collected from pediatric patients with a prior diagnosis of FCD; 75 patients (35 females, 10.1 ± 6.5 years) for analysis of thalamic volume and 68 patients (32 females, 10.2 ± 6.4 years) for DTI analysis. DTI scans were taken at 3 Tesla MRI scanners (30 diffusion gradient directions; b= 1000 s/mm 2 and 5 non diffusion-weighted measurements). DTI tractography was performed using the FACT algorithm with an angle threshold of 45 degrees. Manually delineated ROIs were used to compare the hemisphere containing the dysplasia to the contralateral hemisphere and controls. A significant decrease in the volume of the FCD hemisphere thalamus was detected as compared to the contralateral hemisphere. In comparison to controls, there was an observed reduction in tract volume, length, count, FA of thalami, and FA of thalamocortical pathways in FCD patients. FCD patients had higher odds of exhibiting high ADC in both the thalamus and thalamocortical pathways. The data implied a widespread reduction in structural connectivity of the thalamocortical network. MRI analysis suggests a potential influence of FCD on thalamic volume. Copyright © 2018. Published by Elsevier B.V.

  2. Thalamocortical functional connectivity in Lennox-Gastaut syndrome is abnormally enhanced in executive-control and default-mode networks.

    PubMed

    Warren, Aaron E L; Abbott, David F; Jackson, Graeme D; Archer, John S

    2017-12-01

    To identify abnormal thalamocortical circuits in the severe epilepsy of Lennox-Gastaut syndrome (LGS) that may explain the shared electroclinical phenotype and provide potential treatment targets. Twenty patients with a diagnosis of LGS (mean age = 28.5 years) and 26 healthy controls (mean age = 27.6 years) were compared using task-free functional magnetic resonance imaging (MRI). The thalamus was parcellated according to functional connectivity with 10 cortical networks derived using group-level independent component analysis. For each cortical network, we assessed between-group differences in thalamic functional connectivity strength using nonparametric permutation-based tests. Anatomical locations were identified by quantifying spatial overlap with a histologically informed thalamic MRI atlas. In both groups, posterior thalamic regions showed functional connectivity with visual, auditory, and sensorimotor networks, whereas anterior, medial, and dorsal thalamic regions were connected with networks of distributed association cortex (including the default-mode, anterior-salience, and executive-control networks). Four cortical networks (left and right executive-control network; ventral and dorsal default-mode network) showed significantly enhanced thalamic functional connectivity strength in patients relative to controls. Abnormal connectivity was maximal in mediodorsal and ventrolateral thalamic nuclei. Specific thalamocortical circuits are affected in LGS. Functional connectivity is abnormally enhanced between the mediodorsal and ventrolateral thalamus and the default-mode and executive-control networks, thalamocortical circuits that normally support diverse cognitive processes. In contrast, thalamic regions connecting with primary and sensory cortical networks appear to be less affected. Our previous neuroimaging studies show that epileptic activity in LGS is expressed via the default-mode and executive-control networks. Results of the present study suggest that

  3. Increased Amplitude of Thalamocortical Low-Frequency Oscillations in Patients with Migraine

    PubMed Central

    Wilcox, Sophie L.; Veggeberg, Rosanna; Noseda, Rodrigo; Burstein, Rami; Borsook, David; Becerra, Lino

    2016-01-01

    For many years, neurobiological theories have emphasized the importance of neuronal oscillations in the emergence of brain function. At the same time, clinical studies have shown that disturbances or irregularities in brain rhythms may relate to various common neurological conditions, including migraine. Increasing evidence suggests that the CNS plays a fundamental role in the predisposition to develop different forms of headache. Here, we present human imaging data that strongly support the presence of abnormal low-frequency oscillations (LFOs) in thalamocortical networks of patients in the interictal phase of migraine. Our results show that the main source of arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus. In addition, spontaneous LFOs in the thalamus were selectively associated with the headache attack frequency, meaning that the varying amplitude of dysrhythmia could predispose patients to recurrent attacks. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability. We further speculate that the intrinsic dynamics of thalamocortical network oscillations are crucial for early sensory processing and therefore could underlie important pathophysiological processes involved in multisensory integration. SIGNIFICANCE STATEMENT In many cases, migraine attacks are thought to begin centrally. A major obstacle to studying intrinsic brain activity has been the identification of the precise anatomical structures and functional networks that are involved in migraine. Here, we present imaging data that strongly support the presence of abnormal low-frequency oscillations in thalamocortical networks of patients in the interictal phase of migraine. This arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus and was selectively associated with headache attack

  4. Cocaine acute "binge" administration results in altered thalamocortical interactions in mice.

    PubMed

    Urbano, Francisco J; Bisagno, Verónica; Wikinski, Silvia I; Uchitel, Osvaldo D; Llinás, Rodolfo R

    2009-10-15

    Abnormalities in both thalamic and cortical areas have been reported in human cocaine addicts with noninvasive functional magnetic resonance imaging. Given the substantial involvement of the thalamocortical system in sensory processing and perception, we defined electrophysiology-based protocols to attempt a characterization of cocaine effects on thalamocortical circuits. Thalamocortical function was studied in vivo and in vitro in mice after cocaine "binge" administration. In vivo awake electroencephalography (EEG) was implemented in mice injected with saline, 1 hour or 24 hours after the last cocaine "binge" injection. In vitro current- and voltage-clamp whole-cell patch-clamp recordings were performed from slices including thalamic relay ventrobasal (VB) neurons. In vivo EEG recordings after cocaine "binge" administration showed a significant increment, compared with saline, in low frequencies while observing no changes in high-frequency gamma activity. In vitro patch recordings from VB neurons after cocaine "binge" administration showed low threshold spikes activation at more negative membrane potentials and increments in both I(h) and low voltage activated T-type calcium currents. Also, a 10-mV negative shift on threshold activation level of T-type current and a remarkable increment in both frequency and amplitudes of gamma-aminobutyric acid-A-mediated minis were observed. Our data indicate that thalamocortical dysfunctions observed in cocaine abusers might be due to two distinct but additive events: 1) increased low frequency oscillatory thalamocortical activity, and 2) overinhibition of VB neurons that can abnormally "lock" the whole thalamocortical system at low frequencies.

  5. 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.

  6. Thalamic miR-338-3p mediates auditory thalamocortical disruption and its late onset in 22q11.2 microdeletion models

    PubMed Central

    Chun, Sungkun; Du, Fei; Westmoreland, Joby J.; Han, Seung Baek; Wang, Yong-Dong; Eddins, Donnie; Bayazitov, Ildar T.; Devaraju, Prakash; Yu, Jing; Mellado Lagarde, Marcia M.; Anderson, Kara; Zakharenko, Stanislav S.

    2016-01-01

    Although 22q11.2 deletion syndrome (22q11DS) is associated with early-life behavioral abnormalities, affected individuals are also at high risk for the development of schizophrenia symptoms, including psychosis, later in life. Auditory thalamocortical projections recently emerged as a neural circuit specifically disrupted in 22q11DS mouse models, in which haploinsufficiency of the microRNA-processing gene Dgcr8 resulted in the elevation of the dopamine receptor Drd2 in the auditory thalamus, an abnormal sensitivity of thalamocortical projections to antipsychotics, and an abnormal acoustic-startle response. Here we show that these auditory thalamocortical phenotypes have a delayed onset in 22q11DS mouse models and are associated with an age-dependent reduction of the microRNA miR-338-3p, which targets Drd2 and is enriched in the thalamus of both humans and mice. Replenishing depleted miR-338-3p in mature 22q11DS mice rescued the thalamocortical abnormalities, and miR-338-3p deletion/knockdown mimicked thalamocortical and behavioral deficits and eliminated their age dependence. Therefore, miR-338-3p depletion is necessary and sufficient to disrupt auditory thalamocortical signaling in 22q11DS mouse models and may mediate the pathogenic mechanism of 22q11DS-related psychosis and control its late onset. PMID:27892953

  7. Thalamocortical dysconnectivity in schizophrenia

    PubMed Central

    Woodward, Neil D.; Karbasforoushan, Haleh; Heckers, Stephan

    2013-01-01

    Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies revealed thalamic abnormalities in schizophrenia; however, it is not known if thalamocortical networks are differentially affected in the disorder. To explore this possibility, we examined functional connectivity in intrinsic low frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional magnetic resonance imaging. Method 77 healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, we parceled the cortex into six regions-of-interest; prefrontal, motor, somatosensory, temporal, posterior parietal, and occipital cortex. Mean BOLD time-series was extracted from each of the regions-of-interest and entered into a seed-based functional connectivity analysis. Results Consistent with prior reports, activity in distinct cortical areas correlated with specific, largely non-overlapping regions of the thalamus in both healthy subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local grey matter content within the thalamus and antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, and occipital cortex connectivity with the thalamus. Conclusions This study establishes differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation. PMID:23032387

  8. Review of thalamocortical resting-state fMRI studies in schizophrenia

    PubMed Central

    Giraldo-Chica, Monica; Woodward, Neil D.

    2017-01-01

    Brain circuitry underlying cognition, emotion, and perception is abnormal in schizophrenia. There is considerable evidence that the neuropathology of schizophrenia includes the thalamus, a key hub of cortical-subcortical circuitry and an important regulator of cortical activity. However, the thalamus is a heterogeneous structure composed of several nuclei with distinct inputs and cortical connections. Limitations of conventional neuroimaging methods and conflicting findings from post-mortem investigations have made it difficult to determine if thalamic pathology in schizophrenia is widespread or limited to specific thalamocortical circuits. Resting-state fMRI has proven invaluable for understanding the large-scale functional organization of the brain and investigating neural circuitry relevant to psychiatric disorders. This article summarizes resting-state fMRI investigations of thalamocortical functional connectivity in schizophrenia. Particular attention is paid to the course, diagnostic specificity, and clinical correlates of thalamocortical network dysfunction. PMID:27531067

  9. Stimulus-induced Epileptic Spike-Wave Discharges in Thalamocortical Model with Disinhibition

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Liu, Suyu; Wang, Qingyun

    2016-11-01

    Epileptic absence seizure characterized by the typical 2-4 Hz spike-wave discharges (SWD) are known to arise due to the physiologically abnormal interactions within the thalamocortical network. By introducing a second inhibitory neuronal population in the cortical system, here we propose a modified thalamocortical field model to mathematically describe the occurrences and transitions of SWD under the mutual functions between cortex and thalamus, as well as the disinhibitory modulations of SWD mediated by the two different inhibitory interneuronal populations. We first show that stimulation can induce the recurrent seizures of SWD in the modified model. Also, we demonstrate the existence of various types of firing states including the SWD. Moreover, we can identify the bistable parametric regions where the SWD can be both induced and terminated by stimulation perturbations applied in the background resting state. Interestingly, in the absence of stimulation disinhibitory functions between the two different interneuronal populations can also both initiate and abate the SWD, which suggests that the mechanism of disinhibition is comparable to the effect of stimulation in initiating and terminating the epileptic SWD. Hopefully, the obtained results can provide theoretical evidences in exploring dynamical mechanism of epileptic seizures.

  10. Maturing Thalamocortical Functional Connectivity Across Development

    PubMed Central

    Fair, Damien A.; Bathula, Deepti; Mills, Kathryn L.; Dias, Taciana G. Costa; Blythe, Michael S.; Zhang, Dongyang; Snyder, Abraham Z.; Raichle, Marcus E.; Stevens, Alexander A.; Nigg, Joel T.; Nagel, Bonnie J.

    2010-01-01

    Recent years have witnessed a surge of investigations examining functional brain organization using resting-state functional connectivity MRI (rs-fcMRI). To date, this method has been used to examine systems organization in typical and atypical developing populations. While the majority of these investigations have focused on cortical–cortical interactions, cortical–subcortical interactions also mature into adulthood. Innovative work by Zhang et al. (2008) in adults have identified methods that utilize rs-fcMRI and known thalamo-cortical topographic segregation to identify functional boundaries in the thalamus that are remarkably similar to known thalamic nuclear grouping. However, despite thalamic nuclei being well formed early in development, the developmental trajectory of functional thalamo-cortical relations remains unexplored. Thalamic maps generated by rs-fcMRI are based on functional relationships, and should modify with the dynamic thalamo-cortical changes that occur throughout maturation. To examine this possibility, we employed a strategy as previously described by Zhang et al. to a sample of healthy children, adolescents, and adults. We found strengthening functional connectivity of the cortex with dorsal/anterior subdivisions of the thalamus, with greater connectivity observed in adults versus children. Temporal lobe connectivity with ventral/midline/posterior subdivisions of the thalamus weakened with age. Changes in sensory and motor thalamo-cortical interactions were also identified but were limited. These findings are consistent with known anatomical and physiological cortical–subcortical changes over development. The methods and developmental context provided here will be important for understanding how cortical–subcortical interactions relate to models of typically developing behavior and developmental neuropsychiatric disorders. PMID:20514143

  11. Efficient implementation of a real-time estimation system for thalamocortical hidden Parkinsonian properties

    NASA Astrophysics Data System (ADS)

    Yang, Shuangming; Deng, Bin; Wang, Jiang; Li, Huiyan; Liu, Chen; Fietkiewicz, Chris; Loparo, Kenneth A.

    2017-01-01

    Real-time estimation of dynamical characteristics of thalamocortical cells, such as dynamics of ion channels and membrane potentials, is useful and essential in the study of the thalamus in Parkinsonian state. However, measuring the dynamical properties of ion channels is extremely challenging experimentally and even impossible in clinical applications. This paper presents and evaluates a real-time estimation system for thalamocortical hidden properties. For the sake of efficiency, we use a field programmable gate array for strictly hardware-based computation and algorithm optimization. In the proposed system, the FPGA-based unscented Kalman filter is implemented into a conductance-based TC neuron model. Since the complexity of TC neuron model restrains its hardware implementation in parallel structure, a cost efficient model is proposed to reduce the resource cost while retaining the relevant ionic dynamics. Experimental results demonstrate the real-time capability to estimate thalamocortical hidden properties with high precision under both normal and Parkinsonian states. While it is applied to estimate the hidden properties of the thalamus and explore the mechanism of the Parkinsonian state, the proposed method can be useful in the dynamic clamp technique of the electrophysiological experiments, the neural control engineering and brain-machine interface studies.

  12. Optogenetic rewiring of thalamocortical circuits to restore function in the stroke injured brain

    PubMed Central

    Tennant, Kelly A.; Taylor, Stephanie L.; White, Emily R.; Brown, Craig E.

    2017-01-01

    To regain sensorimotor functions after stroke, surviving neural circuits must reorganize and form new connections. Although the thalamus is critical for processing and relaying sensory information to the cortex, little is known about how stroke affects the structure and function of these connections, or whether a therapeutic approach targeting these circuits can improve recovery. Here we reveal with in vivo calcium imaging that stroke in somatosensory cortex dampens the excitability of surviving thalamocortical circuits. Given this deficit, we hypothesized that chronic transcranial window optogenetic stimulation of thalamocortical axons could facilitate recovery. Using two-photon imaging, we show that optogenetic stimulation promotes the formation of new and stable thalamocortical synaptic boutons, without impacting axon branch dynamics. Stimulation also enhances the recovery of somatosensory cortical circuit function and forepaw sensorimotor abilities. These results demonstrate that an optogenetic approach can rewire thalamocortical circuits and restore function in the damaged brain. PMID:28643802

  13. The ciliogenic transcription factor Rfx3 is required for the formation of the thalamocortical tract by regulating the patterning of prethalamus and ventral telencephalon.

    PubMed

    Magnani, Dario; Morlé, Laurette; Hasenpusch-Theil, Kerstin; Paschaki, Marie; Jacoby, Monique; Schurmans, Stéphane; Durand, Bénédicte; Theil, Thomas

    2015-05-01

    Primary cilia are complex subcellular structures that play key roles during embryogenesis by controlling the cellular response to several signaling pathways. Defects in the function and/or structure of primary cilia underlie a large number of human syndromes collectively referred to as ciliopathies. Often, ciliopathies are associated with mental retardation (MR) and malformation of the corpus callosum. However, the possibility of defects in other forebrain axon tracts, which could contribute to the cognitive disorders of these patients, has not been explored. Here, we investigate the formation of the corticothalamic/thalamocortical tracts in mice mutant for Rfx3, which regulates the expression of many genes involved in ciliogenesis and cilia function. Using DiI axon tracing and immunohistochemistry experiments, we show that some Rfx3(-/-) corticothalamic axons abnormally migrate toward the pial surface of the ventral telencephalon (VT). Some thalamocortical axons (TCAs) also fail to leave the diencephalon or abnormally project toward the amygdala. Moreover, the Rfx3(-/-) VT displays heterotopias containing attractive guidance cues and expressing the guidance molecules Slit1 and Netrin1. Finally, the abnormal projection of TCAs toward the amygdala is also present in mice carrying a mutation in the Inpp5e gene, which is mutated in Joubert Syndrome and which controls cilia signaling and stability. The presence of identical thalamocortical malformations in two independent ciliary mutants indicates a novel role for primary cilia in the formation of the corticothalamic/thalamocortical tracts by establishing the correct cellular environment necessary for its development. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Thalamo-Cortical Connectivity: What Can Diffusion Tractography Tell Us About Reading Difficulties in Children?

    PubMed Central

    Fan, Qiuyun; Davis, Nicole; Anderson, Adam W.

    2014-01-01

    Abstract Reading is an essential skill in modern society, but many people have deficits in the decoding and word recognition aspects of reading, a difficulty often referred to as dyslexia. The primary focus of neuroimaging studies to date in dyslexia has been on cortical regions; however, subcortical regions may also be important for explaining this disability. Here, we used diffusion tensor imaging to examine the association between thalamo-cortical connectivity and children's reading ability in 20 children with typically developed reading ability (age range 8–17/10–17 years old from two imaging centers) and 19 children with developmental dyslexia (DYS) (age range 9–17/9–16 years old). To measure thalamo-cortical connections, the structural images were segmented into cortical and subcortical anatomical regions that were used as target and seed regions in the probabilistic tractography analysis. Abnormal thalamic connectivity was found in the dyslexic group in the sensorimotor and lateral prefrontal cortices. These results suggest that the thalamus may play a key role in reading behavior by mediating the functions of task-specific cortical regions; such findings lay the foundation for future studies to investigate further neurobiological anomalies in the development of thalamo-cortical connectivity in DYS. PMID:24963547

  15. Impaired thalamocortical connectivity in autism spectrum disorder: a study of functional and anatomical connectivity.

    PubMed

    Nair, Aarti; Treiber, Jeffrey M; Shukla, Dinesh K; Shih, Patricia; Müller, Ralph-Axel

    2013-06-01

    The thalamus plays crucial roles in the development and mature functioning of numerous sensorimotor, cognitive and attentional circuits. Currently limited evidence suggests that autism spectrum disorder may be associated with thalamic abnormalities, potentially related to sociocommunicative and other impairments in this disorder. We used functional connectivity magnetic resonance imaging and diffusion tensor imaging probabilistic tractography to study the functional and anatomical integrity of thalamo-cortical connectivity in children and adolescents with autism spectrum disorder and matched typically developing children. For connectivity with five cortical seeds (prefontal, parieto-occipital, motor, somatosensory and temporal), we found evidence of both anatomical and functional underconnectivity. The only exception was functional connectivity with the temporal lobe, which was increased in the autism spectrum disorders group, especially in the right hemisphere. However, this effect was robust only in partial correlation analyses (partialling out time series from other cortical seeds), whereas findings from total correlation analyses suggest that temporo-thalamic overconnectivity in the autism group was only relative to the underconnectivity found for other cortical seeds. We also found evidence of microstructural compromise within the thalamic motor parcel, associated with compromise in tracts between thalamus and motor cortex, suggesting that the thalamus may play a role in motor abnormalities reported in previous autism studies. More generally, a number of correlations of diffusion tensor imaging and functional connectivity magnetic resonance imaging measures with diagnostic and neuropsychological scores indicate involvement of abnormal thalamocortical connectivity in sociocommunicative and cognitive impairments in autism spectrum disorder.

  16. Moderate Cortical Cooling Eliminates Thalamocortical Silent States during Slow Oscillation.

    PubMed

    Sheroziya, Maxim; Timofeev, Igor

    2015-09-23

    Reduction in temperature depolarizes neurons by a partial closure of potassium channels but decreases the vesicle release probability within synapses. Compared with cooling, neuromodulators produce qualitatively similar effects on intrinsic neuronal properties and synapses in the cortex. We used this similarity of neuronal action in ketamine-xylazine-anesthetized mice and non-anesthetized mice to manipulate the thalamocortical activity. We recorded cortical electroencephalogram/local field potential (LFP) activity and intracellular activities from the somatosensory thalamus in control conditions, during cortical cooling and on rewarming. In the deeply anesthetized mice, moderate cortical cooling was characterized by reversible disruption of the thalamocortical slow-wave pattern rhythmicity and the appearance of fast LFP spikes, with frequencies ranging from 6 to 9 Hz. These LFP spikes were correlated with the rhythmic IPSP activities recorded within the thalamic ventral posterior medial neurons and with depolarizing events in the posterior nucleus neurons. Similar cooling of the cortex during light anesthesia rapidly and reversibly eliminated thalamocortical silent states and evoked thalamocortical persistent activity; conversely, mild heating increased thalamocortical slow-wave rhythmicity. In the non-anesthetized head-restrained mice, cooling also prevented the generation of thalamocortical silent states. We conclude that moderate cortical cooling might be used to manipulate slow-wave network activity and induce neuromodulator-independent transition to activated states. Significance statement: In this study, we demonstrate that moderate local cortical cooling of lightly anesthetized or naturally sleeping mice disrupts thalamocortical slow oscillation and induces the activated local field potential pattern. Mild heating has the opposite effect; it increases the rhythmicity of thalamocortical slow oscillation. Our results demonstrate that slow oscillation can be

  17. Role of inhibitory feedback for information processing in thalamocortical circuits

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

    Mayer, Joerg; Schuster, Heinz Georg; Claussen, Jens Christian

    2006-03-15

    The information transfer in the thalamus is blocked dynamically during sleep, in conjunction with the occurrence of spindle waves. In order to describe the dynamic mechanisms which control the sensory transfer of information, it is necessary to have a qualitative model for the response properties of thalamic neurons. As the theoretical understanding of the mechanism remains incomplete, we analyze two modeling approaches for a recent experiment by Le Masson et al. [Nature (London) 417, 854 (2002)] on the thalamocortical loop. We use a conductance based model in order to motivate an extension of the Hindmarsh-Rose model, which mimics experimental observationsmore » of Le Masson et al. Typically, thalamic neurons posses two different firing modes, depending on their membrane potential. At depolarized potentials, the cells fire in a single spike mode and relay synaptic inputs in a one-to-one manner to the cortex. If the cell gets hyperpolarized, T-type calcium currents generate burst-mode firing which leads to a decrease in the spike transfer. In thalamocortical circuits, the cell membrane gets hyperpolarized by recurrent inhibitory feedback loops. In the case of reciprocally coupled excitatory and inhibitory neurons, inhibitory feedback leads to metastable self-sustained oscillations, which mask the incoming input, and thereby reduce the information transfer significantly.« less

  18. Global Intracellular Slow-Wave Dynamics of the Thalamocortical System

    PubMed Central

    Sheroziya, Maxim

    2014-01-01

    It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like “modulator” EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs (“drivers”) were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing “driver”- and “modulator”-like EPSPs, others showing “modulator”-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display “hub dynamics” and thus may contribute to the generation of cortical slow waves. PMID:24966387

  19. Thalamocortical Connections and Executive Function in Pediatric Temporal and Frontal Lobe Epilepsy.

    PubMed

    Law, N; Smith, M L; Widjaja, E

    2018-06-07

    Largely accepted in the literature is the role the interconnections between the thalamus and cortex play in generalized epilepsy. However, thalamocortical involvement is less understood in focal epilepsy in terms of the effect of seizures on thalamocortical circuitry in the developing brain and subsequent cognitive outcome. We investigated thalamocortical pathway microstructure in pediatric frontal lobe epilepsy and temporal lobe epilepsy and examined the associations between pathway microstructure and measures of executive function. We examined thalamocortical connections in 24 children with frontal lobe epilepsy, 17 patients with temporal lobe epilepsy, and 25 healthy children using DTI. We investigated several executive function measures in patients and controls, which were distilled into latent executive function components to compare among groups, and the associations between measures of thalamocortical microstructure and executive function. We found no differences in thalamocortical pathway microstructure between the groups, but aspects of executive function (mental flexibility/inhibition/shifting) were impaired in the frontal lobe epilepsy group compared with controls. In patients with frontal lobe epilepsy, younger age at seizure onset and a greater number of antiepileptic drugs were associated with DTI indices indicative of damaged/less developed thalamocortical pathways. In patients with temporal lobe epilepsy, poorer performance on all measures of executive function was associated with DTI indices reflective of damaged/less developed pathways. Our results give insight into vulnerable neural networks in pediatric focal epilepsy and suggest thalamocortical pathway damage as a potential mechanism of executive function impairment in temporal lobe epilepsy but not frontal lobe epilepsy. Identifying structure-function relations can help inform how we measure functional and cognitive/behavioral outcomes in these populations. © 2018 by American Journal of

  20. Opposing Effects of Maternal Hypo- and Hyperthyroidism on the Stability of Thalamocortical Synapses in the Visual Cortex of Adult Offspring.

    PubMed

    Strobl, Marie-Therese J; Freeman, Daniel; Patel, Jenica; Poulsen, Ryan; Wendler, Christopher C; Rivkees, Scott A; Coleman, Jason E

    2017-05-01

    Insufficient or excessive thyroid hormone (TH) levels during fetal development can cause long-term neurological and cognitive problems. Studies in animal models of perinatal hypo- and hyperthyroidism suggest that these problems may be a consequence of the formation of maladaptive circuitry in the cerebral cortex, which can persist into adulthood. Here we used mouse models of maternal hypo- and hyperthyroidism to investigate the long-term effects of altering thyroxine (T4) levels during pregnancy (corresponding to embryonic days 6.5-18.5) on thalamocortical (TC) axon dynamics in adult offspring. Because perinatal hypothyroidism has been linked to visual processing deficits in humans, we performed chronic two-photon imaging of TC axons and boutons in primary visual cortex (V1). We found that a decrease or increase in maternal serum T4 levels was associated with atypical steady-state dynamics of TC axons and boutons in V1 of adult offspring. Hypothyroid offspring exhibited axonal branch and bouton dynamics indicative of an abnormal increase in TC connectivity, whereas changes in hyperthyroid offspring were indicative of an abnormal decrease in TC connectivity. Collectively, our data suggest that alterations to prenatal T4 levels can cause long-term synaptic instability in TC circuits, which could impair early stages of visual processing. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Convergence of Cortical and Sensory Driver Inputs on Single Thalamocortical Cells

    PubMed Central

    Groh, Alexander; Bokor, Hajnalka; Mease, Rebecca A.; Plattner, Viktor M.; Hangya, Balázs; Stroh, Albrecht; Deschenes, Martin; Acsády, László

    2014-01-01

    Ascending and descending information is relayed through the thalamus via strong, “driver” pathways. According to our current knowledge, different driver pathways are organized in parallel streams and do not interact at the thalamic level. Using an electron microscopic approach combined with optogenetics and in vivo physiology, we examined whether driver inputs arising from different sources can interact at single thalamocortical cells in the rodent somatosensory thalamus (nucleus posterior, POm). Both the anatomical and the physiological data demonstrated that ascending driver inputs from the brainstem and descending driver inputs from cortical layer 5 pyramidal neurons converge and interact on single thalamocortical neurons in POm. Both individual pathways displayed driver properties, but they interacted synergistically in a time-dependent manner and when co-activated, supralinearly increased the output of thalamus. As a consequence, thalamocortical neurons reported the relative timing between sensory events and ongoing cortical activity. We conclude that thalamocortical neurons can receive 2 powerful inputs of different origin, rather than only a single one as previously suggested. This allows thalamocortical neurons to integrate raw sensory information with powerful cortical signals and transfer the integrated activity back to cortical networks. PMID:23825316

  2. Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness

    PubMed Central

    Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R.

    2015-01-01

    In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca2+ channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states. PMID:26056284

  3. Altered thalamocortical rhythmicity and connectivity in mice lacking CaV3.1 T-type Ca2+ channels in unconsciousness.

    PubMed

    Choi, Soonwook; Yu, Eunah; Lee, Seongwon; Llinás, Rodolfo R

    2015-06-23

    In unconscious status (e.g., deep sleep and anesthetic unconsciousness) where cognitive functions are not generated there is still a significant level of brain activity present. Indeed, the electrophysiology of the unconscious brain is characterized by well-defined thalamocortical rhythmicity. Here we address the ionic basis for such thalamocortical rhythms during unconsciousness. In particular, we address the role of CaV3.1 T-type Ca(2+) channels, which are richly expressed in thalamic neurons. Toward this aim, we examined the electrophysiological and behavioral phenotypes of mice lacking CaV3.1 channels (CaV3.1 knockout) during unconsciousness induced by ketamine or ethanol administration. Our findings indicate that CaV3.1 KO mice displayed attenuated low-frequency oscillations in thalamocortical loops, especially in the 1- to 4-Hz delta band, compared with control mice (CaV3.1 WT). Intriguingly, we also found that CaV3.1 KO mice exhibited augmented high-frequency oscillations during unconsciousness. In a behavioral measure of unconsciousness dynamics, CaV3.1 KO mice took longer to fall into the unconscious state than controls. In addition, such unconscious events had a shorter duration than those of control mice. The thalamocortical interaction level between mediodorsal thalamus and frontal cortex in CaV3.1 KO mice was significantly lower, especially for delta band oscillations, compared with that of CaV3.1 WT mice, during unconsciousness. These results suggest that the CaV3.1 channel is required for the generation of a given set of thalamocortical rhythms during unconsciousness. Further, that thalamocortical resonant neuronal activity supported by this channel is important for the control of vigilance states.

  4. Development of thalamocortical connectivity during infancy and its cognitive correlations.

    PubMed

    Alcauter, Sarael; Lin, Weili; Smith, J Keith; Short, Sarah J; Goldman, Barbara D; Reznick, J Steven; Gilmore, John H; Gao, Wei

    2014-07-02

    Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy. Copyright © 2014 the authors 0270-6474/14/349067-09$15.00/0.

  5. Intracortical multiplication of thalamocortical signals in mouse auditory cortex.

    PubMed

    Li, Ling-yun; Li, Ya-tang; Zhou, Mu; Tao, Huizhong W; Zhang, Li I

    2013-09-01

    Cortical processing of sensory information begins with the transformation of thalamically relayed signals. We optogenetically silenced intracortical circuits to isolate thalamic inputs to layer 4 neurons and found that intracortical excitation linearly amplified thalamocortical responses underlying frequency and direction selectivity, with spectral range and tuning preserved, and prolonged the response duration. This signal pre-amplification and prolongation enhanced the salience of thalamocortically relayed information and ensured its robust, faithful and more persistent representation.

  6. Abnormal dynamics of language in schizophrenia.

    PubMed

    Stephane, Massoud; Kuskowski, Michael; Gundel, Jeanette

    2014-05-30

    Language could be conceptualized as a dynamic system that includes multiple interactive levels (sub-lexical, lexical, sentence, and discourse) and components (phonology, semantics, and syntax). In schizophrenia, abnormalities are observed at all language elements (levels and components) but the dynamic between these elements remains unclear. We hypothesize that the dynamics between language elements in schizophrenia is abnormal and explore how this dynamic is altered. We, first, investigated language elements with comparable procedures in patients and healthy controls. Second, using measures of reaction time, we performed multiple linear regression analyses to evaluate the inter-relationships among language elements and the effect of group on these relationships. Patients significantly differed from controls with respect to sub-lexical/lexical, lexical/sentence, and sentence/discourse regression coefficients. The intercepts of the regression slopes increased in the same order above (from lower to higher levels) in patients but not in controls. Regression coefficients between syntax and both sentence level and discourse level semantics did not differentiate patients from controls. This study indicates that the dynamics between language elements is abnormal in schizophrenia. In patients, top-down flow of linguistic information might be reduced, and the relationship between phonology and semantics but not between syntax and semantics appears to be altered. Published by Elsevier Ireland Ltd.

  7. Thalamocortical and corticothalamic pathways differentially contribute to goal-directed behaviors in the rat

    PubMed Central

    Alcaraz, Fabien; Fresno, Virginie; Marchand, Alain R; Kremer, Eric J; Coutureau, Etienne

    2018-01-01

    Highly distributed neural circuits are thought to support adaptive decision-making in volatile and complex environments. Notably, the functional interactions between prefrontal and reciprocally connected thalamic nuclei areas may be important when choices are guided by current goal value or action-outcome contingency. We examined the functional involvement of selected thalamocortical and corticothalamic pathways connecting the dorsomedial prefrontal cortex (dmPFC) and the mediodorsal thalamus (MD) in the behaving rat. Using a chemogenetic approach to inhibit projection-defined dmPFC and MD neurons during an instrumental learning task, we show that thalamocortical and corticothalamic pathways differentially support goal attributes. Both pathways participate in adaptation to the current goal value, but only thalamocortical neurons are required to integrate current causal relationships. These data indicate that antiparallel flow of information within thalamocortical circuits may convey qualitatively distinct aspects of adaptive decision-making and highlight the importance of the direction of information flow within neural circuits. PMID:29405119

  8. Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons.

    PubMed

    Amarillo, Yimy; Tissone, Angela I; Mato, Germán; Nadal, Marcela S

    2018-06-01

    Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current I Kir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of I Kir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of I Kir and hyperpolarization-activated cationic current I h that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that I Kir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with I h and increases the robustness of low threshold-activated calcium current I T -mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current I Kir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that I Kir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current I h ; and increases the robustness of oscillations mediated by the low threshold-activated calcium

  9. Thalamocortical mechanisms for integrating musical tone and rhythm

    PubMed Central

    Musacchia, Gabriella; Large, Edward

    2014-01-01

    Studies over several decades have identified many of the neuronal substrates of music perception by pursuing pitch and rhythm perception separately. Here, we address the question of how these mechanisms interact, starting with the observation that the peripheral pathways of the so-called “Core” and “Matrix” thalamocortical system provide the anatomical bases for tone and rhythm channels. We then examine the hypothesis that these specialized inputs integrate tonal content within rhythm context in auditory cortex using classical types of “driving” and “modulatory” mechanisms. This hypothesis provides a framework for deriving testable predictions about the early stages of music processing. Furthermore, because thalamocortical circuits are shared by speech and music processing, such a model provides concrete implications for how music experience contributes to the development of robust speech encoding mechanisms. PMID:24103509

  10. Modulation of thalamocortical oscillations by TRIP8b, an auxiliary subunit for HCN channels.

    PubMed

    Zobeiri, Mehrnoush; Chaudhary, Rahul; Datunashvili, Maia; Heuermann, Robert J; Lüttjohann, Annika; Narayanan, Venu; Balfanz, Sabine; Meuth, Patrick; Chetkovich, Dane M; Pape, Hans-Christian; Baumann, Arnd; van Luijtelaar, Gilles; Budde, Thomas

    2018-04-01

    Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels have important functions in controlling neuronal excitability and generating rhythmic oscillatory activity. The role of tetratricopeptide repeat-containing Rab8b-interacting protein (TRIP8b) in regulation of hyperpolarization-activated inward current, I h , in the thalamocortical system and its functional relevance for the physiological thalamocortical oscillations were investigated. A significant decrease in I h current density, in both thalamocortical relay (TC) and cortical pyramidal neurons was found in TRIP8b-deficient mice (TRIP8b -/- ). In addition basal cAMP levels in the brain were found to be decreased while the availability of the fast transient A-type K + current, I A , in TC neurons was increased. These changes were associated with alterations in intrinsic properties and firing patterns of TC neurons, as well as intrathalamic and thalamocortical network oscillations, revealing a significant increase in slow oscillations in the delta frequency range (0.5-4 Hz) during episodes of active-wakefulness. In addition, absence of TRIP8b suppresses the normal desynchronization response of the EEG during the switch from slow-wave sleep to wakefulness. It is concluded that TRIP8b is necessary for the modulation of physiological thalamocortical oscillations due to its direct effect on HCN channel expression in thalamus and cortex and that mechanisms related to reduced cAMP signaling may contribute to the present findings.

  11. Potential long-term effects of MDMA on the basal ganglia-thalamocortical circuit: a proton MR spectroscopy and diffusion-tensor imaging study.

    PubMed

    Liu, Hua-Shan; Chou, Ming-Chung; Chung, Hsiao-Wen; Cho, Nai-Yu; Chiang, Shih-Wei; Wang, Chao-Ying; Kao, Hung-Wen; Huang, Guo-Shu; Chen, Cheng-Yu

    2011-08-01

    To investigate the effects of 3,4-methylenedioxymethamphetamine (MDMA, commonly known as "ecstasy") on the alterations of brain metabolites and anatomic tissue integrity related to the function of the basal ganglia-thalamocortical circuit by using proton magnetic resonance (MR) spectroscopy and diffusion-tensor MR imaging. This study was approved by a local institutional review board, and written informed consent was obtained from all subjects. Thirty-one long-term (>1 year) MDMA users and 33 healthy subjects were enrolled. Proton MR spectroscopy from the middle frontal cortex and bilateral basal ganglia and whole-brain diffusion-tensor MR imaging were performed with a 3.0-T system. Absolute concentrations of metabolites were computed, and diffusion-tensor data were registered to the International Consortium for Brain Mapping template to facilitate voxel-based group comparison. The mean myo-inositol level in the basal ganglia of MDMA users (left: 4.55 mmol/L ± 2.01 [standard deviation], right: 4.48 mmol/L ± 1.33) was significantly higher than that in control subjects (left: 3.25 mmol/L ± 1.30, right: 3.31 mmol/L ± 1.19) (P < .001). Cumulative lifetime MDMA dose showed a positive correlation with the levels of choline-containing compounds (Cho) in the right basal ganglia (r = 0.47, P = .02). MDMA users also showed a significant increase in fractional anisotropy (FA) in the bilateral thalami and significant changes in water diffusion in several regions related to the basal ganglia-thalamocortical circuit as compared with control subjects (P < .05; cluster size, >50 voxels). Increased myo-inositol and Cho concentrations in the basal ganglia of MDMA users are suggestive of glial response to degenerating serotonergic functions. The abnormal metabolic changes in the basal ganglia may consequently affect the inhibitory effect of the basal ganglia to the thalamus, as suggested by the increased FA in the thalamus and abnormal changes in water diffusion in the

  12. Presynaptic serotonin 2A receptors modulate thalamocortical plasticity and associative learning

    PubMed Central

    Barre, Alexander; Berthoux, Coralie; De Bundel, Dimitri; Valjent, Emmanuel; Bockaert, Joël; Marin, Philippe; Bécamel, Carine

    2016-01-01

    Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)2A receptors play an essential role in cortical network activity, but the mechanism underlying their modulation of glutamatergic transmission and plasticity at thalamocortical synapses remains largely unexplored. Here, we show that 5-HT2A receptor activation enhances NMDA transmission and gates the induction of temporal-dependent plasticity mediated by NMDA receptors at thalamocortical synapses in acute PFC slices. Expressing 5-HT2A receptors in the mediodorsal thalamus (presynaptic site) of 5-HT2A receptor-deficient mice, but not in the PFC (postsynaptic site), using a viral gene-delivery approach, rescued the otherwise absent potentiation of NMDA transmission, induction of temporal plasticity, and deficit in associative memory. These results provide, to our knowledge, the first physiological evidence of a role of presynaptic 5-HT2A receptors located at thalamocortical synapses in the control of thalamofrontal connectivity and the associated cognitive functions. PMID:26903620

  13. Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD.

    PubMed

    Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y; Dapretto, Mirella

    2017-05-01

    Recent evidence for abnormal thalamic connectivity in autism spectrum disorders (ASD) and sensory processing disorders suggests the thalamus may play a role in sensory over-responsivity (SOR), an extreme negative response to sensory stimuli, which is common in ASD. However, there is yet little understanding of changes in thalamic connectivity during exposure to aversive sensory inputs in individuals with ASD. In particular, the pulvinar nucleus of the thalamus is implicated in atypical sensory processing given its role in selective attention, regulation, and sensory integration. This study aimed to examine the role of pulvinar connectivity in ASD during mildly aversive sensory input. Functional magnetic resonance imaging was used to examine connectivity with the pulvinar during exposure to mildly aversive auditory and tactile stimuli in 38 youth (age 9-17; 19 ASD, 19 IQ-matched typically developing (TD)). Parents rated children's SOR severity on two standard scales. Compared to TD, ASD participants displayed aberrant modulation of connectivity between pulvinar and cortex (including sensory-motor and prefrontal regions) during sensory stimulation. In ASD participants, pulvinar-amygdala connectivity was correlated with severity of SOR symptoms. Deficits in modulation of thalamocortical connectivity in youth with ASD may reflect reduced thalamo-cortical inhibition in response to sensory stimulation, which could lead to difficulty filtering out and/or integrating sensory information. An increase in amygdala connectivity with the pulvinar might be partially responsible for deficits in selective attention as the amygdala signals the brain to attend to distracting sensory stimuli. Autism Res 2017, 10: 801-809. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

  14. The thalamo-cortical auditory receptive fields: regulation by the states of vigilance, learning and the neuromodulatory systems.

    PubMed

    Edeline, Jean-Marc

    2003-12-01

    The goal of this review is twofold. First, it aims to describe the dynamic regulation that constantly shapes the receptive fields (RFs) and maps in the thalamo-cortical sensory systems of undrugged animals. Second, it aims to discuss several important issues that remain unresolved at the intersection between behavioral neurosciences and sensory physiology. A first section presents the RF modulations observed when an undrugged animal spontaneously shifts from waking to slow-wave sleep or to paradoxical sleep (also called REM sleep). A second section shows that, in contrast with the general changes described in the first section, behavioral training can induce selective effects which favor the stimulus that has acquired significance during learning. A third section reviews the effects triggered by two major neuromodulators of the thalamo-cortical system--acetylcholine and noradrenaline--which are traditionally involved both in the switch of vigilance states and in learning experiences. The conclusion argues that because the receptive fields and maps of an awake animal are continuously modulated from minute to minute, learning-induced sensory plasticity can be viewed as a "crystallization" of the receptive fields and maps in one of the multiple possible states. Studying the interplays between neuromodulators can help understanding the neurobiological foundations of this dynamic regulation.

  15. 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

  16. Distinct kinetics of inhibitory currents in thalamocortical neurons that arise from dendritic or axonal origin.

    PubMed

    Yang, Sunggu; Govindaiah, Gubbi; Lee, Sang-Hun; Yang, Sungchil; Cox, Charles L

    2017-01-01

    Thalamocortical neurons in the dorsal lateral geniculate nucleus (dLGN) transfer visual information from retina to primary visual cortex. This information is modulated by inhibitory input arising from local interneurons and thalamic reticular nucleus (TRN) neurons, leading to alterations of receptive field properties of thalamocortical neurons. Local GABAergic interneurons provide two distinct synaptic outputs: axonal (F1 terminals) and dendritic (F2 terminals) onto dLGN thalamocortical neurons. By contrast, TRN neurons provide only axonal output (F1 terminals) onto dLGN thalamocortical neurons. It is unclear if GABAA receptor-mediated currents originating from F1 and F2 terminals have different characteristics. In the present study, we examined multiple characteristics (rise time, slope, halfwidth and decay τ) of GABAA receptor-mediated miniature inhibitory postsynaptic synaptic currents (mIPSCs) originating from F1 and F2 terminals. The mIPSCs arising from F2 terminals showed slower kinetics relative to those from F1 terminals. Such differential kinetics of GABAAR-mediated responses could be an important role in temporal coding of visual signals.

  17. Thalamocortical Dysrhythmia: A Theoretical Update in Tinnitus

    PubMed Central

    De Ridder, Dirk; Vanneste, Sven; Langguth, Berthold; Llinas, Rodolfo

    2015-01-01

    Tinnitus is the perception of a sound in the absence of a corresponding external sound source. Pathophysiologically it has been attributed to bottom-up deafferentation and/or top-down noise-cancelling deficit. Both mechanisms are proposed to alter auditory ­thalamocortical signal transmission, resulting in thalamocortical dysrhythmia (TCD). In deafferentation, TCD is characterized by a slowing down of resting state alpha to theta activity associated with an increase in surrounding gamma activity, resulting in persisting cross-frequency coupling between theta and gamma activity. Theta burst-firing increases network synchrony and recruitment, a mechanism, which might enable long-range synchrony, which in turn could represent a means for finding the missing thalamocortical information and for gaining access to consciousness. Theta oscillations could function as a carrier wave to integrate the tinnitus-related focal auditory gamma activity in a consciousness enabling network, as envisioned by the global workspace model. This model suggests that focal activity in the brain does not reach consciousness, except if the focal activity becomes functionally coupled to a consciousness enabling network, aka the global workspace. In limited deafferentation, the missing information can be retrieved from the auditory cortical neighborhood, decreasing surround inhibition, resulting in TCD. When the deafferentation is too wide in bandwidth, it is hypothesized that the missing information is retrieved from theta-mediated parahippocampal auditory memory. This suggests that based on the amount of deafferentation TCD might change to parahippocampocortical persisting and thus pathological theta–gamma rhythm. From a Bayesian point of view, in which the brain is conceived as a prediction machine that updates its memory-based predictions through sensory updating, tinnitus is the result of a prediction error between the predicted and sensed auditory input. The decrease in sensory updating

  18. Analysis of the role of the low threshold currents IT and Ih in intrinsic delta oscillations of thalamocortical neurons

    PubMed Central

    Amarillo, Yimy; Mato, Germán; Nadal, Marcela S.

    2015-01-01

    Thalamocortical neurons are involved in the generation and maintenance of brain rhythms associated with global functional states. The repetitive burst firing of TC neurons at delta frequencies (1–4 Hz) has been linked to the oscillations recorded during deep sleep and during episodes of absence seizures. To get insight into the biophysical properties that are the basis for intrinsic delta oscillations in these neurons, we performed a bifurcation analysis of a minimal conductance-based thalamocortical neuron model including only the IT channel and the sodium and potassium leak channels. This analysis unveils the dynamics of repetitive burst firing of TC neurons, and describes how the interplay between the amplifying variable mT and the recovering variable hT of the calcium channel IT is sufficient to generate low threshold oscillations in the delta band. We also explored the role of the hyperpolarization activated cationic current Ih in this reduced model and determine that, albeit not required, Ih amplifies and stabilizes the oscillation. PMID:25999847

  19. Analysis of the role of the low threshold currents IT and Ih in intrinsic delta oscillations of thalamocortical neurons.

    PubMed

    Amarillo, Yimy; Mato, Germán; Nadal, Marcela S

    2015-01-01

    Thalamocortical neurons are involved in the generation and maintenance of brain rhythms associated with global functional states. The repetitive burst firing of TC neurons at delta frequencies (1-4 Hz) has been linked to the oscillations recorded during deep sleep and during episodes of absence seizures. To get insight into the biophysical properties that are the basis for intrinsic delta oscillations in these neurons, we performed a bifurcation analysis of a minimal conductance-based thalamocortical neuron model including only the IT channel and the sodium and potassium leak channels. This analysis unveils the dynamics of repetitive burst firing of TC neurons, and describes how the interplay between the amplifying variable mT and the recovering variable hT of the calcium channel IT is sufficient to generate low threshold oscillations in the delta band. We also explored the role of the hyperpolarization activated cationic current Ih in this reduced model and determine that, albeit not required, Ih amplifies and stabilizes the oscillation.

  20. Cell Type–Specific Three-Dimensional Structure of Thalamocortical Circuits in a Column of Rat Vibrissal Cortex

    PubMed Central

    de Kock, Christiaan P. J.; Bruno, Randy M.; Ramirez, Alejandro; Meyer, Hanno S.; Dercksen, Vincent J.; Helmstaedter, Moritz; Sakmann, Bert

    2012-01-01

    Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamocortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined cortical column in rat vibrissal cortex. We objectively classify 9 cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamocortical synapses. Somata and dendrites of most cell types intermingle, while thalamocortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamocortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type–specific lemniscal synaptic wiring diagram and elucidates structure–function relationships of this physiologically relevant pathway at single-cell resolution. PMID:22089425

  1. Self-sustained asynchronous irregular states and Up-Down states in thalamic, cortical and thalamocortical networks of nonlinear integrate-and-fire neurons.

    PubMed

    Destexhe, Alain

    2009-12-01

    Randomly-connected networks of integrate-and-fire (IF) neurons are known to display asynchronous irregular (AI) activity states, which resemble the discharge activity recorded in the cerebral cortex of awake animals. However, it is not clear whether such activity states are specific to simple IF models, or if they also exist in networks where neurons are endowed with complex intrinsic properties similar to electrophysiological measurements. Here, we investigate the occurrence of AI states in networks of nonlinear IF neurons, such as the adaptive exponential IF (Brette-Gerstner-Izhikevich) model. This model can display intrinsic properties such as low-threshold spike (LTS), regular spiking (RS) or fast-spiking (FS). We successively investigate the oscillatory and AI dynamics of thalamic, cortical and thalamocortical networks using such models. AI states can be found in each case, sometimes with surprisingly small network size of the order of a few tens of neurons. We show that the presence of LTS neurons in cortex or in thalamus, explains the robust emergence of AI states for relatively small network sizes. Finally, we investigate the role of spike-frequency adaptation (SFA). In cortical networks with strong SFA in RS cells, the AI state is transient, but when SFA is reduced, AI states can be self-sustained for long times. In thalamocortical networks, AI states are found when the cortex is itself in an AI state, but with strong SFA, the thalamocortical network displays Up and Down state transitions, similar to intracellular recordings during slow-wave sleep or anesthesia. Self-sustained Up and Down states could also be generated by two-layer cortical networks with LTS cells. These models suggest that intrinsic properties such as adaptation and low-threshold bursting activity are crucial for the genesis and control of AI states in thalamocortical networks.

  2. Combined Effects of Feedforward Inhibition and Excitation in Thalamocortical Circuit on the Transitions of Epileptic Seizures

    PubMed Central

    Fan, Denggui; Duan, Lixia; Wang, Qian; Luan, Guoming

    2017-01-01

    The mechanisms underlying electrophysiologically observed two-way transitions between absence and tonic-clonic epileptic seizures in cerebral cortex remain unknown. The interplay within thalamocortical network is believed to give rise to these epileptic multiple modes of activity and transitions between them. In particular, it is thought that in some areas of cortex there exists feedforward inhibition from specific relay nucleus of thalamus (TC) to inhibitory neuronal population (IN) which has even more stronger functions on cortical activities than the known feedforward excitation from TC to excitatory neuronal population (EX). Inspired by this, we proposed a modified computational model by introducing feedforward inhibitory connectivity within thalamocortical circuit, to systematically investigate the combined effects of feedforward inhibition and excitation on transitions of epileptic seizures. We first found that the feedforward excitation can induce the transition from tonic oscillation to spike and wave discharges (SWD) in cortex, i.e., the epileptic tonic-absence seizures, with the fixed weak feedforward inhibition. Thereinto, the phase of absence seizures corresponding to strong feedforward excitation can be further transformed into the clonic oscillations with the increasing of feedforward inhibition, representing the epileptic absence-clonic seizures. We also observed the other fascinating dynamical states, such as periodic 2/3/4-spike and wave discharges, reversed SWD and clonic oscillations, as well as saturated firings. More importantly, we can identify the stable parameter regions representing the tonic-clonic oscillations and SWD discharges of epileptic seizures on the 2-D plane composed of feedforward inhibition and excitation, where the physiologically plausible transition pathways between tonic-clonic and absence seizures can be figured out. These results indicate the functional role of feedforward pathways in controlling epileptic seizures and

  3. Thalamocortical Dysfunction and Thalamic Injury after Asphyxial Cardiac Arrest in Developing Rats

    PubMed Central

    Shoykhet, Michael; Simons, Daniel J.; Alexander, Henry; Hosler, Christina; Kochanek, Patrick M.; Clark, Robert S. B.

    2012-01-01

    Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic Reticular Nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on post-natal day 17. We found that 48–72 hours after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6–8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine min of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the Reticular Nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest. PMID:22492052

  4. Mean-field modeling of the basal ganglia-thalamocortical system. II Dynamics of parkinsonian oscillations.

    PubMed

    van Albada, S J; Gray, R T; Drysdale, P M; Robinson, P A

    2009-04-21

    Neuronal correlates of Parkinson's disease (PD) include a shift to lower frequencies in the electroencephalogram (EEG) and enhanced synchronized oscillations at 3-7 and 7-30 Hz in the basal ganglia, thalamus, and cortex. This study describes the dynamics of a recent physiologically based mean-field model of the basal ganglia-thalamocortical system, and shows how it accounts for many key electrophysiological correlates of PD. Its detailed functional connectivity comprises partially segregated direct and indirect pathways through two populations of striatal neurons, a hyperdirect pathway involving a corticosubthalamic projection, thalamostriatal feedback, and local inhibition in striatum and external pallidum (GPe). In a companion paper, realistic steady-state firing rates were obtained for the healthy state, and after dopamine loss modeled by weaker direct and stronger indirect pathways, reduced intrapallidal inhibition, lower firing thresholds of the GPe and subthalamic nucleus (STN), a stronger projection from striatum to GPe, and weaker cortical interactions. Here it is shown that oscillations around 5 and 20 Hz can arise with a strong indirect pathway, which also causes increased synchronization throughout the basal ganglia. Furthermore, increased theta power with progressive nigrostriatal degeneration is correlated with reduced alpha power and peak frequency, in agreement with empirical results. Unlike the hyperdirect pathway, the indirect pathway sustains oscillations with phase relationships that coincide with those found experimentally. Alterations in the responses of basal ganglia to transient stimuli accord with experimental observations. Reduced cortical gains due to both nigrostriatal and mesocortical dopamine loss lead to slower changes in cortical activity and may be related to bradykinesia. Finally, increased EEG power found in some studies may be partly explained by a lower effective GPe firing threshold, reduced GPe-GPe inhibition, and/or weaker

  5. Development of the Thalamocortical Interactions: Past, Present and Future.

    PubMed

    López-Bendito, Guillermina

    2018-06-20

    For the past two decades, we have advanced in our understanding of the mechanisms implicated in the formation of brain circuits. The connection between the cortex and thalamus has deserved much attention, as thalamocortical connectivity is crucial for sensory processing and motor learning. Classical dye tracing studies in wild-type and knockout mice initially helped to characterize the developmental progression of this connectivity and revealed key transcription factors involved. With the recent advances in technical tools to specifically label subsets of projecting neurons, knock-down genes individually and/or modify their activity, the field has gained further understanding on the rules operating in thalamocortical circuit formation and plasticity. In this review, I will summarize the most relevant discoveries that have been made in this field, from development to early plasticity processes covering three major aspects: axon guidance, thalamic influence on sensory cortical specification, and the role of spontaneous thalamic activity. I will emphasize how the implementation of new tools has helped the field to progress and what I consider to be open questions and the perspective for the future. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. Oxotremorine suppresses thalamocortical oscillations via thalamic muscarinic acetylcholine receptors.

    PubMed

    Puoliväli, J; Jäkälä, P; Koivisto, E; Riekkinen, P

    1998-12-01

    We investigated whether the local intrathalamic infusion of a muscarinic acetylcholine receptor agonist (oxotremorine) at either the reticular nucleus of thalamus (NRT) or the ventroposteromedial nucleus of thalamus (VPM) suppresses thalamocortically generated neocortical high-voltage spindles (HVSs). In addition, we studied whether the intracerebroventricular (ICV) infusion of a selective muscarinic M2 acetylcholine receptor antagonist (methoctramine) could block the suppression of HVSs induced by either systemic (IP) administration of an anticholinesterase drug [tetrahydroaminoacridine (THA)] or ICV infusion of oxotremorine in rats. Intrathalamic administration of oxotremorine at 3 and 15 microg in the NRT, and at 15 microg in the VPM suppressed HVSs. ICV oxotremorine at 30 and 100 microg and IP THA at 3 mg/kg decreased HVSs. ICV methoctramine at 100 microg increased HVSs and completely blocked the decrease in HVSs produced by oxotremorine 100 microg and THA 3 mg/kg. The results suggest that activation of muscarinic M2 acetylcholine receptors in thalamic nuclei (NRT and VPM) can suppress thalamocortical oscillations and that ICV or systemically administered drugs that activate either directly (oxotremorine and methoctramine) or indirectly (THA) the muscarinic M2 acetylcholine receptors may modulate neocortical HVSs via the thalamus.

  7. Progressive thalamocortical neuron loss in Cln5 deficient mice: distinct effects in Finnish variant late infantile NCL

    PubMed Central

    von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

    2009-01-01

    Finnish variant LINCL (vLINCLFin) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCLFin, these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL. PMID:19385065

  8. Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.

    PubMed

    von Schantz, Carina; Kielar, Catherine; Hansen, Stine N; Pontikis, Charlie C; Alexander, Noreen A; Kopra, Outi; Jalanko, Anu; Cooper, Jonathan D

    2009-05-01

    Finnish variant LINCL (vLINCL(Fin)) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCL(Fin), these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.

  9. Noninvasive evaluation of corneal abnormalities using static and dynamic light scattering

    NASA Astrophysics Data System (ADS)

    Ansari, Rafat R.; Misra, Anup K.; Leung, Alfred B.; King, James F.; Datiles, Manuel B., III

    2002-06-01

    A preliminary study of corneal abnormalities in intact bovine eyes is presented. Twenty-one eyes were treated with chemicals, cotton swabs, and radial and photo-refractive surgeries. Dynamic and static light scattering was performed as a function of the penetration depth into the corneal tissue. Topographical maps of corneal refractive power from untreated and treated corneas were also obtained using videokeratoscopy and results compared. The ultimate aim is to develop the technique of dynamic light scattering (DLS) for clinical applications in early evaluation of corneal complications after laser-assisted in situ keratomileusis (LASIK) surgeries and other corneal abnormalities.

  10. Thalamocortical Oscillations in the Sleeping and Aroused Brain

    NASA Astrophysics Data System (ADS)

    Steriade, Mircea; McCormick, David A.; Sejnowski, Terrence J.

    1993-10-01

    Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.

  11. Interactions between core and matrix thalamocortical projections in human sleep spindle synchronization

    PubMed Central

    Bonjean, Maxime; Baker, Tanya; Bazhenov, Maxim; Cash, Sydney; Halgren, Eric; Sejnowski, Terrence

    2012-01-01

    Sleep spindles, which are bursts of 11–15 Hz that occur during non-REM sleep, are highly synchronous across the scalp when measured with EEG, but have low spatial coherence and exhibit low correlation with EEG signals when simultaneously measured with MEG spindles in humans. We developed a computational model to explore the hypothesis that the spatial coherence of the EEG spindle is a consequence of diffuse matrix projections of the thalamus to layer 1 compared to the focal projections of the core pathway to layer 4 recorded by the MEG. Increasing the fanout of thalamocortical connectivity in the matrix pathway while keeping the core pathway fixed led to increased synchrony of the spindle activity in the superficial cortical layers in the model. In agreement with cortical recordings, the latency for spindles to spread from the core to the matrix was independent of the thalamocortical fanout but highly dependent on the probability of connections between cortical areas. PMID:22496571

  12. Modafinil enhances thalamocortical activity by increasing neuronal electrotonic coupling

    PubMed Central

    Urbano, Francisco J.; Leznik, Elena; Llinás, Rodolfo R.

    2007-01-01

    Modafinil (Provigil, Modiodal), an antinarcoleptic and mood-enhancing drug, is shown here to sharpen thalamocortical activity and to increase electrical coupling between cortical interneurons and between nerve cells in the inferior olivary nucleus. After irreversible pharmacological block of connexin permeability (i.e., by using either 18β-glycyrrhetinic derivatives or mefloquine), modafinil restored electrotonic coupling within 30 min. It was further established that this restoration is implemented through a Ca2+/calmodulin protein kinase II-dependent step. PMID:17640897

  13. Abnormal Sleep/Wake Dynamics in Orexin Knockout Mice

    PubMed Central

    Diniz Behn, Cecilia G.; Klerman, Elizabeth B.; Mochizuki, Takatoshi; Lin, Shih-Chieh; Scammell, Thomas E.

    2010-01-01

    Study Objectives: Narcolepsy with cataplexy is caused by a loss of orexin (hypocretin) signaling, but the physiologic mechanisms that result in poor maintenance of wakefulness and fragmented sleep remain unknown. Conventional scoring of sleep cannot reveal much about the process of transitioning between states or the variations within states. We developed an EEG spectral analysis technique to determine whether the state instability in a mouse model of narcolepsy reflects abnormal sleep or wake states, faster movements between states, or abnormal transitions between states. Design: We analyzed sleep recordings in orexin knockout (OXKO) mice and wild type (WT) littermates using a state space analysis technique. This non-categorical approach allows quantitative and unbiased examination of sleep/wake states and state transitions. Measurements and Results: OXKO mice spent less time in deep, delta-rich NREM sleep and in active, theta-rich wake and instead spent more time near the transition zones between states. In addition, while in the midst of what should be stable wake, OXKO mice initiated rapid changes into NREM sleep with high velocities normally seen only in transition regions. Consequently, state transitions were much more frequent and rapid even though the EEG progressions during state transitions were normal. Conclusions: State space analysis enables visualization of the boundaries between sleep and wake and shows that narcoleptic mice have less distinct and more labile states of sleep and wakefulness. These observations provide new perspectives on the abnormal state dynamics resulting from disrupted orexin signaling and highlight the usefulness of state space analysis in understanding narcolepsy and other sleep disorders. Citation: Diniz Behn CG; Klerman EB; Mochizuki T; Lin S; Scammell TE. Abnormal sleep/wake dynamics in orexin knockout mice. SLEEP 2010;33(3):297-306. PMID:20337187

  14. Thalamocortical dynamics of the McCollough effect: boundary-surface alignment through perceptual learning.

    PubMed

    Grossberg, Stephen; Hwang, Seungwoo; Mingolla, Ennio

    2002-05-01

    This article further develops the FACADE neural model of 3-D vision and figure-ground perception to quantitatively explain properties of the McCollough effect (ME). The model proposes that many ME data result from visual system mechanisms whose primary function is to adaptively align, through learning, boundary and surface representations that are positionally shifted due to the process of binocular fusion. For example, binocular boundary representations are shifted by binocular fusion relative to monocular surface representations, yet the boundaries must become positionally aligned with the surfaces to control binocular surface capture and filling-in. The model also includes perceptual reset mechanisms that use habituative transmitters in opponent processing circuits. Thus the model shows how ME data may arise from a combination of mechanisms that have a clear functional role in biological vision. Simulation results with a single set of parameters quantitatively fit data from 13 experiments that probe the nature of achromatic/chromatic and monocular/binocular interactions during induction of the ME. The model proposes how perceptual learning, opponent processing, and habituation at both monocular and binocular surface representations are involved, including early thalamocortical sites. In particular, it explains the anomalous ME utilizing these multiple processing sites. Alternative models of the ME are also summarized and compared with the present model.

  15. A chronometric functional sub-network in the thalamo-cortical system regulates the flow of neural information necessary for conscious cognitive processes.

    PubMed

    León-Domínguez, Umberto; Vela-Bueno, Antonio; Froufé-Torres, Manuel; León-Carrión, Jose

    2013-06-01

    The thalamo-cortical system has been defined as a neural network associated with consciousness. While there seems to be wide agreement that the thalamo-cortical system directly intervenes in vigilance and arousal, a divergence of opinion persists regarding its intervention in the control of other cognitive processes necessary for consciousness. In the present manuscript, we provide a review of recent scientific findings on the thalamo-cortical system and its role in the control and regulation of the flow of neural information necessary for conscious cognitive processes. We suggest that the axis formed by the medial prefrontal cortex and different thalamic nuclei (reticular nucleus, intralaminar nucleus, and midline nucleus), represents a core component for consciousness. This axis regulates different cerebral structures which allow basic cognitive processes like attention, arousal and memory to emerge. In order to produce a synchronized coherent response, neural communication between cerebral structures must have exact timing (chronometry). Thus, a chronometric functional sub-network within the thalamo-cortical system keeps us in an optimal and continuous functional state, allowing high-order cognitive processes, essential to awareness and qualia, to take place. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Further evidences for sleep instability and impaired spindle-delta dynamics in schizophrenia: a whole-night polysomnography study with neuroloop-gain and sleep-cycle analysis.

    PubMed

    Sasidharan, Arun; Kumar, Sunil; Nair, Ajay Kumar; Lukose, Ammu; Marigowda, Vrinda; John, John P; Kutty, Bindu M

    2017-10-01

    Sleep offers a unique window into the brain dysfunctions in schizophrenia. Many past sleep studies have reported abnormalities in both macro-sleep architecture (like increased awakenings) as well as micro-sleep-architecture (like spindle deficits) in patients with schizophrenia (PSZ). The present study attempts to replicate previous reports of macro- and micro-sleep-architectural abnormalities in schizophrenia. In addition, the study also examined sleep-stage changes and spindle-delta dynamics across sleep-cycles to provide further evidence in support of the dysfunctional thalamocortical mechanisms causing sleep instability and poor sleep maintenance associated with schizophrenia pathophysiology. Whole-night polysomnography was carried out among 45 PSZ and 39 age- and gender-matched healthy control subjects. Sleep-stage dynamics were assessed across sleep-cycles using a customized software algorithm. Spindle-delta dynamics across sleep-cycles were determined using neuroloop-gain analysis. PSZ showed macro-sleep architecture abnormalities such as prolonged sleeplessness, increased intermittent-awakenings, long sleep-onset latency, reduced non-rapid eye movement (NREM) stage 2 sleep, increased stage transitions, and poor sleep efficiency. They also showed reduced spindle density (sigma neuroloop-gain) but comparable slow wave density (delta neuroloop-gain) throughout the sleep. Sleep-cycle-wise analysis revealed transient features of sleep instability due to significantly increased intermittent awakenings especially in the first and third sleep-cycles, and unstable and recurrent stage transitions in both NREM (first sleep-cycle) and rapid eye movement (REM) sleep-periods (second sleep-cycle). Spindle deficits were persistent across the first three cycles and were positively correlated with sleep disruption during the subsequent REM sleep. In addition to replicating previously reported sleep deficits in PSZ, the current study showed subtle deficits in NREM

  17. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission.

    PubMed

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J

    2016-07-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood. © The Author 2016. Published by Oxford University Press.

  18. Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

    PubMed Central

    Unichenko, Petr; Kirischuk, Sergei; Yang, Jenq-Wei; Baumgart, Jan; Roskoden, Thomas; Schneider, Patrick; Sommer, Angela; Horta, Guilherme; Radyushkin, Konstantin; Nitsch, Robert; Vogt, Johannes; Luhmann, Heiko J.

    2016-01-01

    Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical responses in vivo elicited by single whisker stimulation were comparable in KO and WT mice. In contrast, at P25-31 evoked responses were smaller in amplitude and longer in duration in WT animals, whereas KO mice revealed no such developmental changes. In thalamocortical slices from KO mice, spontaneous activity was increased already at P16-19, and glutamatergic thalamocortical inputs to Layer 4 spiny stellate neurons were potentiated. We conclude that genetic ablation of PRG-1 modulates already at P16-19 spontaneous and evoked excitability of the barrel cortex, including enhancement of thalamocortical glutamatergic inputs to Layer 4, which distorts sensory processing in adulthood. PMID:26980613

  19. Non-Invasive Evaluation of Corneal Abnormalities Using Static and Dynamic Light Scattering

    NASA Technical Reports Server (NTRS)

    Ansari, Rafat R.; Misra, Anup K.; Leung, Alfred B.; King, James F.; Datiles, Manuel B., III

    2002-01-01

    A preliminary study of corneal abnormalities in intact bovine eyes is presented. Twenty-one eyes were treated with chemicals, cotton swabs, and radial and photo-refractive surgeries. Dynamic and static light scattering was performed as a function of the penetration depth into the corneal tissue. Topographical maps of corneal refractive power from untreated and treated corneas were also obtained using videokeratoscopy and results compared. The ultimate aim is to develop the technique of dynamic light scattering (DLS) for clinical applications in early evaluation of corneal complications after laser-assisted in situ keratomileusis (LASIK) surgeries and other corneal abnormalities.

  20. Developmental synchrony of thalamocortical circuits in the neonatal brain.

    PubMed

    Poh, Joann S; Li, Yue; Ratnarajah, Nagulan; Fortier, Marielle V; Chong, Yap-Seng; Kwek, Kenneth; Saw, Seang-Mei; Gluckman, Peter D; Meaney, Michael J; Qiu, Anqi

    2015-08-01

    The thalamus is a deep gray matter structure and consists of axonal fibers projecting to the entire cortex, which provide the anatomical support for its sensorimotor and higher-level cognitive functions. There is limited in vivo evidence on the normal thalamocortical development, especially in early life. In this study, we aimed to investigate the developmental patterns of the cerebral cortex, the thalamic substructures, and their connectivity with the cortex in the first few weeks of the postnatal brain. We hypothesized that there is developmental synchrony of the thalamus, its cortical projections, and corresponding target cortical structures. We employed diffusion tensor imaging (DTI) and divided the thalamus into five substructures respectively connecting to the frontal, precentral, postcentral, temporal, and parietal and occipital cortex. T2-weighted magnetic resonance imaging (MRI) was used to measure cortical thickness. We found age-related increases in cortical thickness of bilateral frontal cortex and left temporal cortex in the early postnatal brain. We also found that the development of the thalamic substructures was synchronized with that of their respective thalamocortical connectivity in the first few weeks of the postnatal life. In particular, the right thalamo-frontal substructure had the fastest growth in the early postnatal brain. Our study suggests that the distinct growth patterns of the thalamic substructures are in synchrony with those of the cortex in early life, which may be critical for the development of the cortical and subcortical functional specialization. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Thalamocortical and intracortical laminar connectivity determines sleep spindle properties.

    PubMed

    Krishnan, Giri P; Rosen, Burke Q; Chen, Jen-Yung; Muller, Lyle; Sejnowski, Terrence J; Cash, Sydney S; Halgren, Eric; Bazhenov, Maxim

    2018-06-27

    Sleep spindles are brief oscillatory events during non-rapid eye movement (NREM) sleep. Spindle density and synchronization properties are different in MEG versus EEG recordings in humans and also vary with learning performance, suggesting spindle involvement in memory consolidation. Here, using computational models, we identified network mechanisms that may explain differences in spindle properties across cortical structures. First, we report that differences in spindle occurrence between MEG and EEG data may arise from the contrasting properties of the core and matrix thalamocortical systems. The matrix system, projecting superficially, has wider thalamocortical fanout compared to the core system, which projects to middle layers, and requires the recruitment of a larger population of neurons to initiate a spindle. This property was sufficient to explain lower spindle density and higher spatial synchrony of spindles in the superficial cortical layers, as observed in the EEG signal. In contrast, spindles in the core system occurred more frequently but less synchronously, as observed in the MEG recordings. Furthermore, consistent with human recordings, in the model, spindles occurred independently in the core system but the matrix system spindles commonly co-occurred with core spindles. We also found that the intracortical excitatory connections from layer III/IV to layer V promote spindle propagation from the core to the matrix system, leading to widespread spindle activity. Our study predicts that plasticity of intra- and inter-cortical connectivity can potentially be a mechanism for increased spindle density as has been observed during learning.

  2. Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input.

    PubMed

    Happel, Max F K; Jeschke, Marcus; Ohl, Frank W

    2010-08-18

    Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determine how concurrent afferent inputs are integrated. Through separate excitatory horizontal projections, terminating in cortical layers II/III, information about stimulus energy in greater spectral distance is provided even over long cortical distances. These projections effectively broaden spectral tuning width. Based on these data, we suggest a mechanism of spectral integration in primary auditory cortex that is based on temporally precise interactions of afferent thalamocortical inputs and different short- and long-range intracortical networks. The proposed conceptual framework allows integration of different and partly controversial anatomical and physiological models of spectral integration in the literature.

  3. Sensory cortex limits cortical maps and drives top-down plasticity in thalamocortical circuits

    PubMed Central

    Zembrzycki, Andreas; Chou, Shen-Ju; Ashery-Padan, Ruth; Stoykova, Anastassia; O’Leary, Dennis D.M.

    2013-01-01

    Summary Primary somatosensory cortex (S1) contains a complete body map that mirrors subcortical maps developed by peripheral sensory input projecting to sensory hindbrain, thalamus, then S1. Peripheral changes during development alter these maps through ‘bottom-up’ plasticity. Unknown is how S1 size influences map organization and if an altered S1 map feedbacks to affect subcortical maps. We show in mice that S1 is significantly reduced by cortex-specific deletion of Pax6, resulting in a reduced body map and loss of body representations by exclusion of later-differentiating sensory thalamocortical input. An initially normal sensory thalamus was re-patterned to match the aberrant S1 map by apoptotic deletion of thalamic neurons representing body parts with axons excluded from S1. Deleted representations were rescued by altering competition between thalamocortical axons by sensory deprivation or increasing S1. Thus, S1 size determined resolution and completeness of body maps and engaged ‘top-down’ plasticity that re-patterned sensory thalamus to match S1. PMID:23831966

  4. The Effects of Grain Size and Texture on Dynamic Abnormal Grain Growth in Mo

    NASA Astrophysics Data System (ADS)

    Noell, Philip J.; Taleff, Eric M.

    2016-10-01

    This is the first report of abnormal grain morphologies specific to a Mo sheet material produced from a commercial-purity arc-melted ingot. Abnormal grains initiated and grew during plastic deformation of this material at temperatures of 1793 K and 1813 K (1520 °C and 1540 °C). This abnormal grain growth during high-temperature plastic deformation is termed dynamic abnormal grain growth, DAGG. DAGG in this material readily consumes nearly all grains near the sheet center while leaving many grains near the sheet surface unconsumed. Crystallographic texture, grain size, and other microstructural features are characterized. After recrystallization, a significant through-thickness variation in crystallographic texture exists in this material but does not appear to directly influence DAGG propagation. Instead, dynamic normal grain growth, which may be influenced by texture, preferentially occurs near the sheet surface prior to DAGG. The large grains thus produced near the sheet surface inhibit the subsequent growth of the abnormal grains produced by DAGG, which preferentially consume the finer grains near the sheet center. This produces abnormal grains that span the sheet center but leave unconsumed polycrystalline microstructure near the sheet surface. Abnormal grains are preferentially oriented with the < 110rangle approximately along the tensile axis. These results provide additional new evidence that boundary curvature is the primary driving force for DAGG in Mo.

  5. Specialization and integration of functional thalamocortical connectivity in the human infant.

    PubMed

    Toulmin, Hilary; Beckmann, Christian F; O'Muircheartaigh, Jonathan; Ball, Gareth; Nongena, Pumza; Makropoulos, Antonios; Ederies, Ashraf; Counsell, Serena J; Kennea, Nigel; Arichi, Tomoki; Tusor, Nora; Rutherford, Mary A; Azzopardi, Denis; Gonzalez-Cinca, Nuria; Hajnal, Joseph V; Edwards, A David

    2015-05-19

    Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions.

  6. Specialization and integration of functional thalamocortical connectivity in the human infant

    PubMed Central

    Toulmin, Hilary; Beckmann, Christian F.; O'Muircheartaigh, Jonathan; Ball, Gareth; Nongena, Pumza; Makropoulos, Antonios; Ederies, Ashraf; Counsell, Serena J.; Kennea, Nigel; Arichi, Tomoki; Tusor, Nora; Rutherford, Mary A.; Azzopardi, Denis; Gonzalez-Cinca, Nuria; Hajnal, Joseph V.; Edwards, A. David

    2015-01-01

    Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions. PMID:25941391

  7. A model of microsaccade-related neural responses induced by short-term depression in thalamocortical synapses

    PubMed Central

    Yuan, Wu-Jie; Dimigen, Olaf; Sommer, Werner; Zhou, Changsong

    2013-01-01

    Microsaccades during fixation have been suggested to counteract visual fading. Recent experiments have also observed microsaccade-related neural responses from cellular record, scalp electroencephalogram (EEG), and functional magnetic resonance imaging (fMRI). The underlying mechanism, however, is not yet understood and highly debated. It has been proposed that the neural activity of primary visual cortex (V1) is a crucial component for counteracting visual adaptation. In this paper, we use computational modeling to investigate how short-term depression (STD) in thalamocortical synapses might affect the neural responses of V1 in the presence of microsaccades. Our model not only gives a possible synaptic explanation for microsaccades in counteracting visual fading, but also reproduces several features in experimental findings. These modeling results suggest that STD in thalamocortical synapses plays an important role in microsaccade-related neural responses and the model may be useful for further investigation of behavioral properties and functional roles of microsaccades. PMID:23630494

  8. Abnormal computerized dynamic posturography findings in dizzy patients with normal ENG results.

    PubMed

    Sataloff, Robert T; Hawkshaw, Mary J; Mandel, Heidi; Zwislewski, Amy B; Armour, Jonathan; Mandel, Steven

    2005-04-01

    The complexities of the balance system create difficulties for professionals interested in testing equilibrium function objectively. Traditionally, electronystagmography (ENG) has been used for this purpose, but it provides information on only a limited portion of the equilibrium system. Computerized dynamic posturography (CDP) is less specific than ENG, but it provides more global insight into a patient's ability to maintain equilibrium under more challenging environmental circumstances. CD Palso appears to be valuable in obtaining objective confirmation of an abnormality in some dizzy patients whose ENG findings are normal. Our review of 33 patients with normal ENG results and abnormal CDP findings suggests that posturography is useful for confirming or quantifying a balance abnormality in some patients whose complaints cannot be confirmed by other tests frequently used by otologists.

  9. Pre-synaptic kainate receptor-mediated facilitation of glutamate release involves PKA and Ca(2+) -calmodulin at thalamocortical synapses.

    PubMed

    Andrade-Talavera, Yuniesky; Duque-Feria, Paloma; Sihra, Talvinder S; Rodríguez-Moreno, Antonio

    2013-09-01

    We have investigated the mechanisms underlying the facilitatory modulation mediated by kainate receptor (KAR) activation in the cortex, using isolated nerve terminals (synaptosomes) and slice preparations. In cortical nerve terminals, kainate (KA, 100 μM) produced an increase in 4-aminopyridine (4-AP)-evoked glutamate release. In thalamocortical slices, KA (1 μM) produced an increase in the amplitude of evoked excitatory post-synaptic currents (eEPSCs) at synapses established between thalamic axon terminals from the ventrobasal nucleus onto stellate neurons of L4 of the somatosensory cortex. In both, synaptosomes and slices, the effect of KA was antagonized by 6-cyano-7-nitroquinoxaline-2,3-dione, and persisted after pre-treatment with a cocktail of antagonists of other receptors whose activation could potentially have produced facilitation of release indirectly. Mechanistically, the observed effects of KA appear to be congruent in synaptosomal and slice preparations. Thus, the facilitation by KA of synaptosomal glutamate release and thalamocortical synaptic transmission were suppressed by the inhibition of protein kinase A and occluded by the stimulation of adenylyl cyclase. Dissecting this G-protein-independent regulation further in thalamocortical slices, the KAR-mediated facilitation of synaptic transmission was found to be sensitive to the block of Ca(2+) permeant KARs by philanthotoxin. Intriguingly, the synaptic facilitation was abrogated by depletion of intracellular Ca(2+) stores by thapsigargin, or inhibition of Ca(2+) -induced Ca(2+) -release by ryanodine. Thus, the KA-mediated modulation was contingent on both Ca(2+) entry through Ca(2+) -permeable KARs and liberation of intracellular Ca(2+) stores. Finally, sensitivity to W-7 indicated that the increased cytosolic [Ca(2+) ] underpinning KAR-mediated regulation of synaptic transmission at thalamocortical synapses, requires downstream activation of calmodulin. We conclude that neocortical pre

  10. Thalamo-cortical activation and connectivity during response preparation in adults with persistent and remitted ADHD.

    PubMed

    Clerkin, Suzanne M; Schulz, Kurt P; Berwid, Olga G; Fan, Jin; Newcorn, Jeffrey H; Tang, Cheuk Y; Halperin, Jeffrey M

    2013-09-01

    The neural correlates of stimulus-driven processes, such as response preparation, have been posited to be associated with the onset of attention deficit hyperactivity disorder (ADHD) while being distinct from the neural mechanisms associated with recovery. The authors tested this hypothesis in adults with remitted and persistent ADHD. Thirty-eight young adults who were diagnosed with combined-type ADHD in childhood (probands) and 32 carefully matched comparison subjects were followed longitudinally and scanned with functional MRI while performing an event-related cued reaction time task. Probands were characterized as individuals with persistent or remitted ADHD. Differences in thalamo-cortical activation and functional connectivity during response preparation between comparison subjects and probands and between individuals with persistent ADHD and those with remitted ADHD were assessed by contrasting neural activation and functional connectivity during cue or noncue events. Probands exhibited less cue-related activation than comparison subjects in the thalamus, anterior cingulate cortex, supplementary motor area, inferior parietal lobe, and dorsolateral prefrontal cortex despite similar overall patterns of activation. There were no differences in activation between individuals in the remitted ADHD group and those in the persistent ADHD group in any hypothesized regions. However, cue-related functional connectivity between the right thalamus and brainstem was greater in comparison subjects relative to probands, and cue-related connectivity was greater between the right thalamus and prefrontal regions in individuals with remitted ADHD relative to those with persistent ADHD. Decreased thalamo-cortical activation during response preparation was present in adults diagnosed with ADHD in childhood regardless of symptom remission in adulthood, and may be partly driven by less functional coordination between the brainstem and thalamus. Greater functional integration of the

  11. Evidence That Descending Cortical Axons Are Essential for Thalamocortical Axons to Cross the Pallial-Subpallial Boundary in the Embryonic Forebrain

    PubMed Central

    Chen, Yijing; Magnani, Dario; Theil, Thomas; Pratt, Thomas; Price, David J.

    2012-01-01

    Developing thalamocortical axons traverse the subpallium to reach the cortex located in the pallium. We tested the hypothesis that descending corticofugal axons are important for guiding thalamocortical axons across the pallial-subpallial boundary, using conditional mutagenesis to assess the effects of blocking corticofugal axonal development without disrupting thalamus, subpallium or the pallial-subpallial boundary. We found that thalamic axons still traversed the subpallium in topographic order but did not cross the pallial-subpallial boundary. Co-culture experiments indicated that the inability of thalamic axons to cross the boundary was not explained by mutant cortex developing a long-range chemorepulsive action on thalamic axons. On the contrary, cortex from conditional mutants retained its thalamic axonal growth-promoting activity and continued to express Nrg-1, which is responsible for this stimulatory effect. When mutant cortex was replaced with control cortex, corticofugal efferents were restored and thalamic axons from conditional mutants associated with them and crossed the pallial-subpallial boundary. Our study provides the most compelling evidence to date that cortical efferents are required to guide thalamocortical axons across the pallial-subpallial boundary, which is otherwise hostile to thalamic axons. These results support the hypothesis that thalamic axons grow from subpallium to cortex guided by cortical efferents, with stimulation from diffusible cortical growth-promoting factors. PMID:22412988

  12. Mechanisms underlying a thalamocortical transformation during active tactile sensation

    PubMed Central

    Gutnisky, Diego Adrian; Yu, Jianing; Hires, Samuel Andrew; To, Minh-Son; Svoboda, Karel

    2017-01-01

    During active somatosensation, neural signals expected from movement of the sensors are suppressed in the cortex, whereas information related to touch is enhanced. This tactile suppression underlies low-noise encoding of relevant tactile features and the brain’s ability to make fine tactile discriminations. Layer (L) 4 excitatory neurons in the barrel cortex, the major target of the somatosensory thalamus (VPM), respond to touch, but have low spike rates and low sensitivity to the movement of whiskers. Most neurons in VPM respond to touch and also show an increase in spike rate with whisker movement. Therefore, signals related to self-movement are suppressed in L4. Fast-spiking (FS) interneurons in L4 show similar dynamics to VPM neurons. Stimulation of halorhodopsin in FS interneurons causes a reduction in FS neuron activity and an increase in L4 excitatory neuron activity. This decrease of activity of L4 FS neurons contradicts the "paradoxical effect" predicted in networks stabilized by inhibition and in strongly-coupled networks. To explain these observations, we constructed a model of the L4 circuit, with connectivity constrained by in vitro measurements. The model explores the various synaptic conductance strengths for which L4 FS neurons actively suppress baseline and movement-related activity in layer 4 excitatory neurons. Feedforward inhibition, in concert with recurrent intracortical circuitry, produces tactile suppression. Synaptic delays in feedforward inhibition allow transmission of temporally brief volleys of activity associated with touch. Our model provides a mechanistic explanation of a behavior-related computation implemented by the thalamocortical circuit. PMID:28591219

  13. Abnormal sleep/wake dynamics in orexin knockout mice.

    PubMed

    Diniz Behn, Cecilia G; Klerman, Elizabeth B; Mochizuki, Takatoshi; Lin, Shih-Chieh; Scammell, Thomas E

    2010-03-01

    Narcolepsy with cataplexy is caused by a loss of orexin (hypocretin) signaling, but the physiologic mechanisms that result in poor maintenance of wakefulness and fragmented sleep remain unknown. Conventional scoring of sleep cannot reveal much about the process of transitioning between states or the variations within states. We developed an EEG spectral analysis technique to determine whether the state instability in a mouse model of narcolepsy reflects abnormal sleep or wake states, faster movements between states, or abnormal transitions between states. We analyzed sleep recordings in orexin knockout (OXKO) mice and wild type (WT) littermates using a state space analysis technique. This non-categorical approach allows quantitative and unbiased examination of sleep/wake states and state transitions. OXKO mice spent less time in deep, delta-rich NREM sleep and in active, theta-rich wake and instead spent more time near the transition zones between states. In addition, while in the midst of what should be stable wake, OXKO mice initiated rapid changes into NREM sleep with high velocities normally seen only in transition regions. Consequently, state transitions were much more frequent and rapid even though the EEG progressions during state transitions were normal. State space analysis enables visualization of the boundaries between sleep and wake and shows that narcoleptic mice have less distinct and more labile states of sleep and wakefulness. These observations provide new perspectives on the abnormal state dynamics resulting from disrupted orexin signaling and highlight the usefulness of state space analysis in understanding narcolepsy and other sleep disorders.

  14. Understanding Epileptiform After-Discharges as Rhythmic Oscillatory Transients.

    PubMed

    Baier, Gerold; Taylor, Peter N; Wang, Yujiang

    2017-01-01

    Electro-cortical activity in patients with epilepsy may show abnormal rhythmic transients in response to stimulation. Even when using the same stimulation parameters in the same patient, wide variability in the duration of transient response has been reported. These transients have long been considered important for the mapping of the excitability levels in the epileptic brain but their dynamic mechanism is still not well understood. To investigate the occurrence of abnormal transients dynamically, we use a thalamo-cortical neural population model of epileptic spike-wave activity and study the interaction between slow and fast subsystems. In a reduced version of the thalamo-cortical model, slow wave oscillations arise from a fold of cycles (FoC) bifurcation. This marks the onset of a region of bistability between a high amplitude oscillatory rhythm and the background state. In vicinity of the bistability in parameter space, the model has excitable dynamics, showing prolonged rhythmic transients in response to suprathreshold pulse stimulation. We analyse the state space geometry of the bistable and excitable states, and find that the rhythmic transient arises when the impending FoC bifurcation deforms the state space and creates an area of locally reduced attraction to the fixed point. This area essentially allows trajectories to dwell there before escaping to the stable steady state, thus creating rhythmic transients. In the full thalamo-cortical model, we find a similar FoC bifurcation structure. Based on the analysis, we propose an explanation of why stimulation induced epileptiform activity may vary between trials, and predict how the variability could be related to ongoing oscillatory background activity. We compare our dynamic mechanism with other mechanisms (such as a slow parameter change) to generate excitable transients, and we discuss the proposed excitability mechanism in the context of stimulation responses in the epileptic cortex.

  15. Estimation of Thalamocortical and Intracortical Network Models from Joint Thalamic Single-Electrode and Cortical Laminar-Electrode Recordings in the Rat Barrel System

    PubMed Central

    Blomquist, Patrick; Devor, Anna; Indahl, Ulf G.; Ulbert, Istvan; Einevoll, Gaute T.; Dale, Anders M.

    2009-01-01

    A new method is presented for extraction of population firing-rate models for both thalamocortical and intracortical signal transfer based on stimulus-evoked data from simultaneous thalamic single-electrode and cortical recordings using linear (laminar) multielectrodes in the rat barrel system. Time-dependent population firing rates for granular (layer 4), supragranular (layer 2/3), and infragranular (layer 5) populations in a barrel column and the thalamic population in the homologous barreloid are extracted from the high-frequency portion (multi-unit activity; MUA) of the recorded extracellular signals. These extracted firing rates are in turn used to identify population firing-rate models formulated as integral equations with exponentially decaying coupling kernels, allowing for straightforward transformation to the more common firing-rate formulation in terms of differential equations. Optimal model structures and model parameters are identified by minimizing the deviation between model firing rates and the experimentally extracted population firing rates. For the thalamocortical transfer, the experimental data favor a model with fast feedforward excitation from thalamus to the layer-4 laminar population combined with a slower inhibitory process due to feedforward and/or recurrent connections and mixed linear-parabolic activation functions. The extracted firing rates of the various cortical laminar populations are found to exhibit strong temporal correlations for the present experimental paradigm, and simple feedforward population firing-rate models combined with linear or mixed linear-parabolic activation function are found to provide excellent fits to the data. The identified thalamocortical and intracortical network models are thus found to be qualitatively very different. While the thalamocortical circuit is optimally stimulated by rapid changes in the thalamic firing rate, the intracortical circuits are low-pass and respond most strongly to slowly varying

  16. Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

    PubMed Central

    Woodward, Neil D.; Heckers, Stephan

    2015-01-01

    Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

  17. Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo.

    PubMed

    Nagaoka, Akira; Takehara, Hiroaki; Hayashi-Takagi, Akiko; Noguchi, Jun; Ishii, Kazuhiko; Shirai, Fukutoshi; Yagishita, Sho; Akagi, Takanori; Ichiki, Takanori; Kasai, Haruo

    2016-05-25

    Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca(2+) signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.

  18. Neuronal plasticity and thalamocortical sleep and waking oscillations

    PubMed Central

    Timofeev, Igor

    2011-01-01

    Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma. PMID:21854960

  19. Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes.

    PubMed

    Wei, Wei; Wang, Xiao-Jing

    2016-12-07

    We developed a circuit model of spiking neurons that includes multiple pathways in the basal ganglia (BG) and is endowed with feedback mechanisms at three levels: cortical microcircuit, corticothalamic loop, and cortico-BG-thalamocortical system. We focused on executive control in a stop signal task, which is known to depend on BG across species. The model reproduces a range of experimental observations and shows that the newly discovered feedback projection from external globus pallidus to striatum is crucial for inhibitory control. Moreover, stopping process is enhanced by the cortico-subcortical reverberatory dynamics underlying persistent activity, establishing interdependence between working memory and inhibitory control. Surprisingly, the stop signal reaction time (SSRT) can be adjusted by weights of certain connections but is insensitive to other connections in this complex circuit, suggesting novel circuit-based intervention for inhibitory control deficits associated with mental illness. Our model provides a unified framework for inhibitory control, decision making, and working memory. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Swimming attenuates d-galactose-induced brain aging via suppressing miR-34a-mediated autophagy impairment and abnormal mitochondrial dynamics.

    PubMed

    Kou, Xianjuan; Li, Jie; Liu, Xingran; Chang, Jingru; Zhao, Qingxia; Jia, Shaohui; Fan, Jingjing; Chen, Ning

    2017-06-01

    microRNAs (miRNAs) have been reported to be involved in many neurodegenerative diseases. To explore the regulatory role of miR-34a in aging-related diseases such as Alzheimer's disease (AD) during exercise intervention, we constructed a rat model with d-galactose (d-gal)-induced oxidative stress and cognitive impairment coupled with dysfunctional autophagy and abnormal mitochondrial dynamics, determined the mitigation of cognitive impairment of d-gal-induced aging rats during swimming intervention, and evaluated miR-34a-mediated functional status of autophagy and abnormal mitochondrial dynamics. Meanwhile, whether the upregulation of miR-34a can lead to dysfunctional autophagy and abnormal mitochondrial dynamics was confirmed in human SH-SY5Y cells with silenced miR-34a by the transfection of a miR-34a inhibitor. Results indicated that swimming intervention could significantly attenuate cognitive impairment, prevent the upregulation of miR-34a, mitigate the dysfunctional autophagy, and inhibit the increase of dynamin-related protein 1 (DRP1) in d-gal-induced aging model rats. In contrast, the miR-34a inhibitor in cell model not only attenuated D-gal-induced the impairment of autophagy but also decreased the expression of DRP1 and mitofusin 2 (MFN2). Therefore, swimming training can delay brain aging of d-gal-induced aging rats through attenuating the impairment of miR-34a-mediated autophagy and abnormal mitochondrial dynamics, and miR-34a could be the novel therapeutic target for aging-related diseases such as AD. NEW & NOTEWORTHY In the present study, we have found that the upregulation of miR-34a is the hallmark of aging or aging-related diseases, which can result in dysfunctional autophagy and abnormal mitochondrial dynamics. In contrast, swimming intervention can delay the aging process by rescuing the impaired functional status of autophagy and abnormal mitochondrial dynamics via the suppression of miR-34a. Copyright © 2017 the American Physiological Society.

  1. Opposite effects of ketamine and deep brain stimulation on rat thalamocortical information processing.

    PubMed

    Kulikova, Sofya P; Tolmacheva, Elena A; Anderson, Paul; Gaudias, Julien; Adams, Brendan E; Zheng, Thomas; Pinault, Didier

    2012-11-01

    Sensory and cognitive deficits are common in schizophrenia. They are associated with abnormal brain rhythms, including disturbances in γ frequency (30-80 Hz) oscillations (GFO) in cortex-related networks. However, the underlying anatomofunctional mechanisms remain elusive. Clinical and experimental evidence suggests that these deficits result from a hyporegulation of glutamate N-methyl-D-aspartate receptors. Here we modeled these deficits in rats with ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist and a translational psychotomimetic substance at subanesthetic doses. We tested the hypothesis that ketamine-induced sensory deficits involve an impairment of the ability of the thalamocortical (TC) system to discriminate the relevant information from the baseline activity. Furthermore, we wanted to assess whether ketamine disrupts synaptic plasticity in TC systems. We conducted multisite network recordings in the rat somatosensory TC system, natural stimulation of the vibrissae and high-frequency electrical stimulation (HFS) of the thalamus. A single systemic injection of ketamine increased the amount of baseline GFO, reduced the amplitude of the sensory-evoked TC response and decreased the power of the sensory-evoked GFO. Furthermore, cortical application of ketamine elicited local and distant increases in baseline GFO. The ketamine effects were transient. Unexpectedly, HFS of the TC pathway had opposite actions. In conclusion, ketamine and thalamic HFS have opposite effects on the ability of the somatosensory TC system to discriminate the sensory-evoked response from the baseline GFO during information processing. Investigating the link between the state and function of the TC system may conceptually be a key strategy to design innovative therapies against neuropsychiatric disorders. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  2. Dynamic changes of striatal and extrastriatal abnormalities in glutaric aciduria type I.

    PubMed

    Harting, Inga; Neumaier-Probst, Eva; Seitz, Angelika; Maier, Esther M; Assmann, Birgit; Baric, Ivo; Troncoso, Monica; Mühlhausen, Chris; Zschocke, Johannes; Boy, Nikolas P S; Hoffmann, Georg F; Garbade, Sven F; Kölker, Stefan

    2009-07-01

    In glutaric aciduria type I, an autosomal recessive disease of mitochondrial lysine, hydroxylysine and tryptophan catabolism, striatal lesions are characteristically induced by acute encephalopathic crises during a finite period of brain development (age 3-36 months). The frequency of striatal injury is significantly less in patients diagnosed as asymptomatic newborns by newborn screening. Most previous studies have focused on the onset and mechanism of striatal injury, whereas little is known about neuroradiological abnormalities in pre-symptomatically diagnosed patients and about dynamic changes of extrastriatal abnormalities. Thus, the major aim of the present retrospective study was to improve our understanding of striatal and extrastriatal abnormalities in affected individuals including those diagnosed by newborn screening. To this end, we systematically analysed magnetic resonance imagings (MRIs) in 38 patients with glutaric aciduria type I diagnosed before or after the manifestation of neurological symptoms. To identify brain regions that are susceptible to cerebral injury during acute encephalopathic crises, we compared the frequency of magnetic resonance abnormalities in patients with and without such crises. Major specific changes after encephalopathic crises were found in the putamen (P < 0.001), nucleus caudatus (P < 0.001), globus pallidus (P = 0.012) and ventricles (P = 0.001). Analysis of empirical cumulative distribution frequencies, however, demonstrated that isolated pallidal abnormalities did not significantly differ over time in both groups (P = 0.544) suggesting that isolated pallidal abnormalities are not induced by acute crises--in contrast to striatal abnormalities. The manifestation of motor disability was associated with signal abnormalities in putamen, caudate, pallidum and ventricles. In addition, we found a large number of extrastriatal abnormalities in patients with and without preceding encephalophatic crises. These abnormalities

  3. Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage.

    PubMed

    Scott, Gregory; Hellyer, Peter J; Ramlackhansingh, Anil F; Brooks, David J; Matthews, Paul M; Sharp, David J

    2015-12-01

    Traumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo. Using [(11)C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage. These findings support a link between axonal damage and persistent inflammation after brain injury.

  4. Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse.

    PubMed

    Evangelio, Marian; García-Amado, María; Clascá, Francisco

    2018-01-01

    A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species.

  5. Thalamocortical Projection Neuron and Interneuron Numbers in the Visual Thalamic Nuclei of the Adult C57BL/6 Mouse

    PubMed Central

    Evangelio, Marian; García-Amado, María; Clascá, Francisco

    2018-01-01

    A key parameter to constrain predictive, bottom-up circuit models of a given brain domain is the number and position of the neuronal populations involved. These include not only the neurons whose bodies reside within the domain, but also the neurons in distant regions that innervate the domain. The mouse visual cortex receives its main subcortical input from the dorsal lateral geniculate nucleus (dLGN) and the lateral posterior (LP) complex of the thalamus. The latter consists of three different nuclei: lateral posterior lateral (LPL), lateral posterior medial rostral (LPMR), and lateral posterior medial caudal (LPMC), each exhibiting specific patterns of connections with the various visual cortical areas. Here, we have determined the number of thalamocortical projection neurons and interneurons in the LP complex and dLGN of the adult C57BL/6 male mouse. We combined Nissl staining and histochemical and immunolabeling methods for consistently delineating nuclei borders, and applied unbiased stereological cell counting methods. Thalamic interneurons were identified using GABA immunolabeling. The C57BL/6 dLGN contains ∼21,200 neurons, while LP complex contains ∼31,000 total neurons. The dLGN and LP are the only nuclei of the mouse dorsal thalamus containing substantial numbers GABA-immunoreactive interneurons. These interneurons, however, are scarcer than previously estimated; they are 5.6% of dLGN neurons and just 1.9% of the LP neurons. It can be thus inferred that the dLGN contains ∼20,000 and the LP complex ∼30,400 thalamocortical projection neurons (∼12,000 in LPL, 15,200 in LPMR, and 4,200 in LPMC). The present dataset is relevant for constraining models of mouse visual thalamocortical circuits, as well as for quantitative comparisons between genetically modified mouse strains, or across species. PMID:29706872

  6. Development of thalamocortical connections between the mediodorsal thalamus and the prefrontal cortex and its implication in cognition

    PubMed Central

    Ferguson, Brielle R.; Gao, Wen-Jun

    2015-01-01

    The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the prefrontal cortex (PFC), and is thought to be highly implicated in modulation of cognitive performance. Additionally, it undergoes highly conserved developmental stages, which, when dysregulated, can have detrimental consequences. Embryonically, the MD experiences a tremendous surge in neurogenesis and differentiation, and disruption of this process may underlie the pathology in certain neurodevelopmental disorders. However, during the postnatal period, a vast amount of cell loss in the MD occurs. These together may represent an extended critical period for postnatal development, in which disturbances in the normal growth or reduction of the MD afferents to the PFC, can result in PFC-dependent cognitive, affective, or psychotic abnormalities. In this review, we explore the current knowledge supporting this hypothesis of a protracted critical period, and propose how developmental changes in the MD contribute to successful prefrontal cortical development and function. Specifically, we elaborate on the unique properties of MD-PFC connections compared with other thalamocortical afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic transmission in the local prefrontal circuitry, and speculate on what occurs during postnatal development, particularly within the early neonatal stage, as well as juvenile and adolescent periods. Finally, we discuss the questions that remain and propose future experiments in order to provide perspective and novel insights into the cause of neuropsychiatric disorders associated with MD-PFC development. PMID:25620923

  7. Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

    PubMed

    Voets, Natalie L; Menke, Ricarda A L; Jbabdi, Saad; Husain, Masud; Stacey, Richard; Carpenter, Katherine; Adcock, Jane E

    2015-11-01

    Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage. © The Author 2015. Published by Oxford University Press.

  8. Dynamic Analysis of the Abnormal Isometric Strength Movement Pattern between Shoulder and Elbow Joint in Patients with Hemiplegia.

    PubMed

    Liu, Yali; Hong, Yuezhen; Ji, Linhong

    2018-01-01

    Patients with hemiplegia usually have weak muscle selectivity and usually perform strength at a secondary joint (secondary strength) during performing a strength at one joint (primary strength). The abnormal strength pattern between shoulder and elbow joint has been analyzed by the maximum value while the performing process with strength changing from 0 to maximum then to 0 was a dynamic process. The objective of this study was to develop a method to dynamically analyze the strength changing process. Ten patients were asked to perform four group asks (maximum and 50% maximum voluntary strength in shoulder abduction, shoulder adduction, elbow flexion, and elbow extension). Strength and activities from seven muscles were measured. The changes of secondary strength had significant correlation with those of primary strength in all tasks ( R > 0.76, p < 0.01). The antagonistic muscles were moderately influenced by the primary strength ( R > 0.4, p < 0.01). Deltoid muscles, biceps brachii, triceps brachii, and brachioradialis had significant influences on the abnormal strength pattern (all p < 0.01). The dynamic method was proved to be efficient to analyze the different influences of muscles on the abnormal strength pattern. The muscles, deltoid muscles, biceps brachii, triceps brachii, and brachioradialis, much influenced the stereotyped movement pattern between shoulder and elbow joint.

  9. Dynamic Analysis of the Abnormal Isometric Strength Movement Pattern between Shoulder and Elbow Joint in Patients with Hemiplegia

    PubMed Central

    2018-01-01

    Patients with hemiplegia usually have weak muscle selectivity and usually perform strength at a secondary joint (secondary strength) during performing a strength at one joint (primary strength). The abnormal strength pattern between shoulder and elbow joint has been analyzed by the maximum value while the performing process with strength changing from 0 to maximum then to 0 was a dynamic process. The objective of this study was to develop a method to dynamically analyze the strength changing process. Ten patients were asked to perform four group asks (maximum and 50% maximum voluntary strength in shoulder abduction, shoulder adduction, elbow flexion, and elbow extension). Strength and activities from seven muscles were measured. The changes of secondary strength had significant correlation with those of primary strength in all tasks (R > 0.76, p < 0.01). The antagonistic muscles were moderately influenced by the primary strength (R > 0.4, p < 0.01). Deltoid muscles, biceps brachii, triceps brachii, and brachioradialis had significant influences on the abnormal strength pattern (all p < 0.01). The dynamic method was proved to be efficient to analyze the different influences of muscles on the abnormal strength pattern. The muscles, deltoid muscles, biceps brachii, triceps brachii, and brachioradialis, much influenced the stereotyped movement pattern between shoulder and elbow joint. PMID:29610654

  10. Thalamo-cortical communication, glutamatergic neurotransmission and neural oscillations: A unique window into the origins of ScZ?

    PubMed

    Pratt, Judith; Dawson, Neil; Morris, Brain J; Grent-'t-Jong, Tineke; Roux, Frederic; Uhlhaas, Peter J

    2017-02-01

    The thalamus has recently received renewed interest in systems-neuroscience and schizophrenia (ScZ) research because of emerging evidence highlighting its important role in coordinating functional interactions in cortical-subcortical circuits. Moreover, higher cognitive functions, such as working memory and attention, have been related to thalamo-cortical interactions, providing a novel perspective for the understanding of the neural substrate of cognition. The current review will support this perspective by summarizing evidence on the crucial role of neural oscillations in facilitating thalamo-cortical (TC) interactions during normal brain functioning and their potential impairment in ScZ. Specifically, we will focus on the relationship between NMDA-R mediated (glutamatergic) neurotransmission in TC-interactions. To this end, we will first review the functional anatomy and neurotransmitters in thalamic circuits, followed by a review of the oscillatory signatures and cognitive processes supported by TC-circuits. In the second part of the paper, data from preclinical research as well as human studies will be summarized that have implicated TC-interactions as a crucial target for NMDA-receptor hypofunctioning. Finally, we will compare these neural signatures with current evidence from ScZ-research, suggesting a potential overlap between alterations in TC-circuits as the result of NMDA-R deficits and stage-specific alterations in large-scale networks in ScZ. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Abnormal early dynamic individual patterns of functional networks in low gamma band for depression recognition.

    PubMed

    Bi, Kun; Chattun, Mahammad Ridwan; Liu, Xiaoxue; Wang, Qiang; Tian, Shui; Zhang, Siqi; Lu, Qing; Yao, Zhijian

    2018-06-13

    The functional networks are associated with emotional processing in depression. The mapping of dynamic spatio-temporal brain networks is used to explore individual performance during early negative emotional processing. However, the dysfunctions of functional networks in low gamma band and their discriminative potentialities during early period of emotional face processing remain to be explored. Functional brain networks were constructed from the MEG recordings of 54 depressed patients and 54 controls in low gamma band (30-48 Hz). Dynamic connectivity regression (DCR) algorithm analyzed the individual change points of time series in response to emotional stimuli and constructed individualized spatio-temporal patterns. The nodal characteristics of patterns were calculated and fed into support vector machine (SVM). Performance of the classification algorithm in low gamma band was validated by dynamic topological characteristics of individual patterns in comparison to alpha and beta band. The best discrimination accuracy of individual spatio-temporal patterns was 91.01% in low gamma band. Individual temporal patterns had better results compared to group-averaged temporal patterns in all bands. The most important discriminative networks included affective network (AN) and fronto-parietal network (FPN) in low gamma band. The sample size is relatively small. High gamma band was not considered. The abnormal dynamic functional networks in low gamma band during early emotion processing enabled depression recognition. The individual information processing is crucial in the discovery of abnormal spatio-temporal patterns in depression during early negative emotional processing. Individual spatio-temporal patterns may reflect the real dynamic function of subjects while group-averaged data may neglect some individual information. Copyright © 2018. Published by Elsevier B.V.

  12. Thalamocortical NMDA conductances and intracortical inhibition can explain cortical temporal tuning

    NASA Technical Reports Server (NTRS)

    Krukowski, A. E.; Miller, K. D.

    2001-01-01

    Cells in cerebral cortex fail to respond to fast-moving stimuli that evoke strong responses in the thalamic nuclei innervating the cortex. The reason for this behavior has remained a mystery. We study an experimentally motivated model of the thalamic input-recipient layer of cat primary visual cortex that accounts for many aspects of cortical orientation tuning. In this circuit, inhibition dominates over excitation, but temporal modulations of excitation and inhibition occur out of phase with one another, allowing excitation to transiently drive cells. We show that this circuit provides a natural explanation of cortical low-pass temporal frequency tuning, provided N-methyl-D-aspartate (NMDA) receptors are present in thalamocortical synapses in proportions measured experimentally. This suggests a new and unanticipated role for NMDA conductances in shaping the temporal response properties of cortical cells, and suggests that common cortical circuit mechanisms underlie both spatial and temporal response tuning.

  13. Netrin-4 regulates thalamocortical axon branching in an activity-dependent fashion.

    PubMed

    Hayano, Yasufumi; Sasaki, Kensuke; Ohmura, Nami; Takemoto, Makoto; Maeda, Yurie; Yamashita, Toshihide; Hata, Yoshio; Kitada, Kazuhiro; Yamamoto, Nobuhiko

    2014-10-21

    Axon branching is remodeled by sensory-evoked and spontaneous neuronal activity. However, the underlying molecular mechanism is largely unknown. Here, we demonstrate that the netrin family member netrin-4 (NTN4) contributes to activity-dependent thalamocortical (TC) axon branching. In the postnatal developmental stages of rodents, ntn4 expression was abundant in and around the TC recipient layers of sensory cortices. Neuronal activity dramatically altered the ntn4 expression level in the cortex in vitro and in vivo. TC axon branching was promoted by exogenous NTN4 and suppressed by depletion of the endogenous protein. Moreover, unc-5 homolog B (Unc5B), which strongly bound to NTN4, was expressed in the sensory thalamus, and knockdown of Unc5B in thalamic cells markedly reduced TC axon branching. These results suggest that NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression.

  14. Dynamic Reorganization of Functional Connectivity Reveals Abnormal Temporal Efficiency in Schizophrenia.

    PubMed

    Sun, Yu; Collinson, Simon L; Suckling, John; Sim, Kang

    2018-06-07

    Emerging evidence suggests that schizophrenia is associated with brain dysconnectivity. Nonetheless, the implicit assumption of stationary functional connectivity (FC) adopted in most previous resting-state functional magnetic resonance imaging (fMRI) studies raises an open question of schizophrenia-related aberrations in dynamic properties of resting-state FC. This study introduces an empirical method to examine the dynamic functional dysconnectivity in patients with schizophrenia. Temporal brain networks were estimated from resting-state fMRI of 2 independent datasets (patients/controls = 18/19 and 53/57 for self-recorded dataset and a publicly available replication dataset, respectively) by the correlation of sliding time-windowed time courses among regions of a predefined atlas. Through the newly introduced temporal efficiency approach and temporal random network models, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found that although prominent temporal small-world properties were revealed in both groups, temporal brain networks of patients with schizophrenia in both datasets showed a significantly higher temporal global efficiency, which cannot be simply attributable to head motion and sampling error. Specifically, we found localized changes of temporal nodal properties in the left frontal, right medial parietal, and subcortical areas that were associated with clinical features of schizophrenia. Our findings demonstrate that altered dynamic FC may underlie abnormal brain function and clinical symptoms observed in schizophrenia. Moreover, we provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network and highlight the potential of aberrant brain dynamic FC in unraveling the pathophysiologic mechanisms of the disease.

  15. 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.

  16. Neural cell adhesion molecule, NCAM, regulates thalamocortical axon pathfinding and the organization of the cortical somatosensory representation in mouse

    PubMed Central

    Enriquez-Barreto, Lilian; Palazzetti, Cecilia; Brennaman, Leann H.; Maness, Patricia F.; Fairén, Alfonso

    2012-01-01

    To study the potential role of neural cell adhesion molecule (NCAM) in the development of thalamocortical (TC) axon topography, wild type, and NCAM null mutant mice were analyzed for NCAM expression, projection, and targeting of TC afferents within the somatosensory area of the neocortex. Here we report that NCAM and its α-2,8-linked polysialic acid (PSA) are expressed in developing TC axons during projection to the neocortex. Pathfinding of TC axons in wild type and null mutant mice was mapped using anterograde DiI labeling. At embryonic day E16.5, null mutant mice displayed misguided TC axons in the dorsal telencephalon, but not in the ventral telencephalon, an intermediate target that initially sorts TC axons toward correct neocortical areas. During the early postnatal period, rostrolateral TC axons within the internal capsule along the ventral telencephalon adopted distorted trajectories in the ventral telencephalon and failed to reach the neocortex in NCAM null mutant animals. NCAM null mutants showed abnormal segregation of layer IV barrels in a restricted portion of the somatosensory cortex. As shown by Nissl and cytochrome oxidase staining, barrels of the anterolateral barrel subfield (ALBSF) and the most distal barrels of the posteromedial barrel subfield (PMBSF) did not segregate properly in null mutant mice. These results indicate a novel role for NCAM in axonal pathfinding and topographic sorting of TC axons, which may be important for the function of specific territories of sensory representation in the somatosensory cortex. PMID:22723769

  17. Synaptic Regulation of a Thalamocortical Circuit Controls Depression-Related Behavior.

    PubMed

    Miller, Oliver H; Bruns, Andreas; Ben Ammar, Imen; Mueggler, Thomas; Hall, Benjamin J

    2017-08-22

    The NMDA receptor (NMDAR) antagonist ketamine elicits a long-lasting antidepressant response in patients with treatment-resistant depression. Understanding how antagonism of NMDARs alters synapse and circuit function is pivotal to developing circuit-based therapies for depression. Using virally induced gene deletion, ex vivo optogenetic-assisted circuit analysis, and in vivo chemogenetics and fMRI, we assessed the role of NMDARs in the medial prefrontal cortex (mPFC) in controlling depression-related behavior in mice. We demonstrate that post-developmental genetic deletion of the NMDAR subunit GluN2B from pyramidal neurons in the mPFC enhances connectivity between the mPFC and limbic thalamus, but not the ventral hippocampus, and reduces depression-like behavior. Using intersectional chemogenetics, we show that activation of this thalamocortical circuit is sufficient to elicit a decrease in despair-like behavior. Our findings reveal that GluN2B exerts input-specific control of pyramidal neuron innervation and identify a medial dorsal thalamus (MDT)→mPFC circuit that controls depression-like behavior. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Quantitative 3D Ultrastructure of Thalamocortical Synapses from the "Lemniscal" Ventral Posteromedial Nucleus in Mouse Barrel Cortex.

    PubMed

    Rodriguez-Moreno, Javier; Rollenhagen, Astrid; Arlandis, Jaime; Santuy, Andrea; Merchan-Pérez, Angel; DeFelipe, Javier; Lübke, Joachim H R; Clasca, Francisco

    2017-07-28

    Thalamocortical synapses from "lemniscal" neurons of the dorsomedial portion of the rodent ventral posteromedial nucleus (VPMdm) are able to induce with remarkable efficacy, despite their relative low numbers, the firing of primary somatosensory cortex (S1) layer 4 (L4) neurons. To which extent this high efficacy depends on structural synaptic features remains unclear. Using both serial transmission (TEM) and focused ion beam milling scanning electron microscopy (FIB/SEM), we 3D-reconstructed and quantitatively analyzed anterogradely labeled VPMdm axons in L4 of adult mouse S1. All VPMdm synapses are asymmetric. Virtually all are established by axonal boutons, 53% of which contact multiple (2-4) elements (overall synapse/bouton ratio = 1.6). Most boutons are large (mean 0.47 μm3), and contain 1-3 mitochondria. Vesicle pools and postsynaptic density (PSD) surface areas are large compared to others in rodent cortex. Most PSDs are complex. Most synapses (83%) are established on dendritic spine heads. Furthermore, 15% of the postsynaptic spines receive a second, symmetric synapse. In addition, 13% of the spine heads have a large protrusion inserted into a membrane pouch of the VPMdm bouton. The unusual combination of structural features in VPMdm synapses is likely to contribute significantly to the high efficacy, strength, and plasticity of these thalamocortical synapses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Mapping thalamocortical network pathology in temporal lobe epilepsy.

    PubMed

    Bernhardt, Boris C; Bernasconi, Neda; Kim, Hosung; Bernasconi, Andrea

    2012-01-10

    Although experimental work has provided evidence that the thalamus is a crucial relay structure in temporal lobe epilepsy (TLE), the relation of the thalamus to neocortical pathology remains unclear. To assess thalamocortical network pathology in TLE, we mapped pointwise patterns of thalamic atrophy and statistically related them to neocortical thinning. We studied cross-sectionally 36 patients with drug-resistant TLE and 19 age- and sex-matched healthy control subjects using high-resolution MRI. To localize thalamic pathology, we converted manual labels into surface meshes using the spherical harmonic description and calculated local deformations relative to a template. In addition, we measured cortical thickness by means of the constrained Laplacian anatomic segmentation using proximity algorithm. Compared with control subjects, patients with TLE showed ipsilateral thalamic atrophy that was located along the medial surface, encompassing anterior, medial, and posterior divisions. Unbiased analysis correlating the degree of medial thalamic atrophy with cortical thickness measurements mapped bilateral frontocentral, lateral temporal, and mesiotemporal cortices. These areas overlapped with those of cortical thinning found when patients were compared with control subjects. Thalamic atrophy intensified with a longer duration of epilepsy and was more severe in patients with a history of febrile convulsions. The degree and distribution of thalamic pathology relates to the topography and extent of neocortical atrophy, lending support to the concept that the thalamus is an important hub in the pathologic network of TLE.

  20. Performance evaluation of a dynamic telepathology system (Panoptiq™) in the morphologic assessment of peripheral blood film abnormalities.

    PubMed

    Goswami, R; Pi, D; Pal, J; Cheng, K; Hudoba De Badyn, M

    2015-06-01

    The study evaluated the performance of a dynamic imaging telepathology system (Panoptiq(™) ) as a diagnostic aid to the identification of peripheral blood film (PBF) abnormalities. The study assumed a laboratory personnel working in a clinical laboratory were operating the telepathology system to seek diagnostic opinion from an external consulting hematopathologist. The study examined 100 blood films, encompassing 23 different hematological diseases, reactive or normal cases. The study revealed that with real-time image transmission in live scanning mode of operation, the telepathology system was able to aid reviewers in achieving excellent accuracy, that is correct interpretation of morphologic abnormalities obtained in 83/84 of the hematologic diseases and 12/12 of the reactive/normal conditions (Sensitivity: 0.99; Specificity: 1.00). In contrast, when only saved static images in digital capture mode of operation were reviewed remotely, interpretative omissions occurred in 8/84 of the hematologic diseases and 0/12 of the reactive/normal conditions (Sensitivity: 0.91; Specificity: 1.00). It is hypothesized that real-time operator-reviewer communication during live scanning played an important role in the identification of key morphologic abnormalities for review. Our study showed the Panoptiq system can be adopted reliably as a dynamic telepathology tool in aiding community laboratories in the triage of PBF cases for external diagnostic consultation. © 2014 John Wiley & Sons Ltd.

  1. Morphological abnormalities in prefrontal surface area and thalamic volume in attention deficit/hyperactivity disorder.

    PubMed

    Batty, Martin J; Palaniyappan, Lena; Scerif, Gaia; Groom, Madeleine J; Liddle, Elizabeth B; Liddle, Peter F; Hollis, Chris

    2015-08-30

    Although previous morphological studies have demonstrated abnormalities in prefrontal cortical thickness in children with attention deficit/hyperactivity disorder (ADHD), studies investigating cortical surface area are lacking. As the development of cortical surface is closely linked to the establishment of thalam-ocortical connections, any abnormalities in the structure of the thalamus are likely to relate to altered cortical surface area. Using a clinically well-defined sample of children with ADHD (n = 25, 1 female) and typically developing controls (n = 24, 1 female), we studied surface area across the cortex to determine whether children with ADHD had reduced thalamic volume that related to prefrontal cortical surface area. Relative to controls, children with ADHD had a significant reduction in thalamic volume and dorsolateral prefrontal cortical area in both hemispheres. Furthermore, children with ADHD with smaller thalamic volumes were found to have greater reductions in surface area, a pattern not evident in the control children. Our results are further evidence of reduced lateral prefrontal cortical area in ADHD. Moreover, for the first time, we have also shown a direct association between thalamic anatomy and frontal anatomy in ADHD, suggesting the pathophysiological process that alters surface area maturation is likely to be linked to the development of the thalamus. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. TERMINAL ARBORS OF AXONS PROJECTING TO THE SOMATOSENSORY CORTEX OF THE ADULT RAT. 2. THE ALTERED MORPHOLOGY OF THALAMOCORTICAL AFFERENTS FOLLOWING NEONATAL INFRAORBITAL NERVE CUT (JOURNAL VERSION)

    EPA Science Inventory

    The organization of the whisker representation within the neocortex of the rat is dependent on an intact periphery during development. To further investigate how alterations in the cortical map arise the authors examined the organization of thalamocortical afferents to the whiske...

  3. Complex patterns of abnormal heartbeats

    NASA Technical Reports Server (NTRS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

    2002-01-01

    Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

  4. Group II and III metabotropic glutamate receptors and the control of the nucleus reticularis thalami input to rat thalamocortical neurones in vitro.

    PubMed

    Turner, J P; Salt, T E

    2003-01-01

    Intracellular recordings were made from neurones in the thalamic reticular nucleus (TRN) and ventro-basal (VB) thalamus in slices of rat midbrain in vitro. Electrical stimulation of the medial lemniscus or TRN resulted in the generation of complex synaptic potentials containing disynaptic inhibitory post-synaptic potentials (IPSPs) in VB thalamocortical neurones. Analysis of the excitatory synaptic responses in TRN neurones indicates they can produce burst output response irrespective of the level of sub-threshold membrane potential. This suggests that network-evoked IPSPs in VB thalamocortical neurones occur following a burst of TRN action potentials. Using ionotropic glutamate receptor antagonists, the activation of these disynaptic events was blocked, and the monosynaptic IPSPs that resulted from the direct activation of the TRN could be isolated. The selective Group II agonists LY354740 (1-10 microM) and N-acetyl-aspartyl-glutamate (NAAG; 100-500 microM) both caused a reversible depression of these monosynaptic TRN IPSPs without any effect on membrane potential or input resistance. Likewise, the specific Group III agonist L-2-amino-4-phosphonobutanoate (10-500 microM), but not (RS)-4-phosphonophenylglycine (1 and 30 microM) also caused a reversible depression of these IPSPs, again without any effect on membrane potential or input resistance.Thus, the IPSPs recorded in VB thalamocortical neurones, evoked by TRN activation, can be depressed by the activation of either Group II or III metabotropic glutamate receptors. This is consistent with the location of these receptor types on the presynaptic terminals of TRN axons in the VB thalamus. This raises the possibility that, during periods of intense excitatory activity, glutamate release could influence the release of GABA from TRN axon terminals in the thalamus. In addition, as NAAG is located in the axons and terminals arising from the TRN, there is the possibility that this dipeptide is also released by these

  5. Short-term dynamics of causal information transfer in thalamocortical networks during natural inputs and microstimulation for somatosensory neuroprosthesis

    PubMed Central

    Semework, Mulugeta; DiStasio, Marcello

    2014-01-01

    Recording the activity of large populations of neurons requires new methods to analyze and use the large volumes of time series data thus created. Fast and clear methods for finding functional connectivity are an important step toward the goal of understanding neural processing. This problem presents itself readily in somatosensory neuroprosthesis (SSNP) research, which uses microstimulation (MiSt) to activate neural tissue to mimic natural stimuli, and has the capacity to potentiate, depotentiate, or even destroy functional connections. As the aim of SSNP engineering is artificially creating neural responses that resemble those observed during natural inputs, a central goal is describing the influence of MiSt on activity structure among groups of neurons, and how this structure may be altered to affect perception or behavior. In this paper, we demonstrate the concept of Granger causality, combined with maximum likelihood methods, applied to neural signals recorded before, during, and after natural and electrical stimulation. We show how these analyses can be used to evaluate the changing interactions in the thalamocortical somatosensory system in response to repeated perturbation. Using LFPs recorded from the ventral posterolateral thalamus (VPL) and somatosensory cortex (S1) in anesthetized rats, we estimated pair-wise functional interactions between functional microdomains. The preliminary results demonstrate input-dependent modulations in the direction and strength of information flow during and after application of MiSt. Cortico-cortical interactions during cortical MiSt and baseline conditions showed the largest causal influence differences, while there was no statistically significant difference between pre- and post-stimulation baseline causal activities. These functional connectivity changes agree with physiologically accepted communication patterns through the network, and their particular parameters have implications for both rehabilitation and brain

  6. The role of the first postmitotic cortical cells in the development of thalamocortical innervation in the reeler mouse.

    PubMed

    Molnár, Z; Adams, R; Goffinet, A M; Blakemore, C

    1998-08-01

    In the mutant mouse reeler, the tangential distribution of thalamocortical fibers is essentially normal, even though neurons of the cortical plate accumulate below the entire early-born preplate population (Caviness et al., 1998). This seems incompatible with the hypothesis that cells of the subplate (the lower component of the preplate in normal mammals) form an axonal scaffold that guides thalamic fibers and act as temporary targets for them (Blakemore and Molnár, 1990, Shatz et al., 1990). We used carbocyanine dyes to trace projections in wild-type and reeler mice between embryonic day 13 and postnatal day 3. Preplate formation and early extension of corticofugal fibers to form a topographic array are indistinguishable in the two phenotypes. So too are the emergence of thalamic axons in topographic order through the primitive internal capsule, their meeting with preplate axons, and their distribution over the preplate scaffold. Distinctive differences appear after the cortical plate begins to accumulate below the preplate of reeler, causing the preplate axons to form oblique fascicles, running through the cortical plate. Thalamic axons then pass through the plate within the same fascicles and accumulate in the "superplate" layer for approximately 2-3 d, before defasciculating and plunging down to terminate deep in the cortical plate, creating the curious "looping" pattern seen in the adult. Thus, thalamocortical innervation in reeler follows the same algorithm of development but in relation to the misplaced population of early-born neurons. Far from challenging the theory that preplate fibers guide thalamic axons, reeler provides strong evidence for it.

  7. Abnormal rich club organization and functional brain dynamics in schizophrenia.

    PubMed

    van den Heuvel, Martijn P; Sporns, Olaf; Collin, Guusje; Scheewe, Thomas; Mandl, René C W; Cahn, Wiepke; Goñi, Joaquín; Hulshoff Pol, Hilleke E; Kahn, René S

    2013-08-01

    The human brain forms a large-scale structural network of regions and interregional pathways. Recent studies have reported the existence of a selective set of highly central and interconnected hub regions that may play a crucial role in the brain's integrative processes, together forming a central backbone for global brain communication. Abnormal brain connectivity may have a key role in the pathophysiology of schizophrenia. To examine the structure of the rich club in schizophrenia and its role in global functional brain dynamics. Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in patients with schizophrenia and matched healthy controls. Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands. Forty-eight patients and 45 healthy controls participated in the study. An independent replication data set of 41 patients and 51 healthy controls was included to replicate and validate significant findings. MAIN OUTCOME(S) AND MEASURES: Measures of rich club organization, connectivity density of rich club connections and connections linking peripheral regions to brain hubs, measures of global brain network efficiency, and measures of coupling between brain structure and functional dynamics. Rich club organization between high-degree hub nodes was significantly affected in patients, together with a reduced density of rich club connections predominantly comprising the white matter pathways that link the midline frontal, parietal, and insular hub regions. This reduction in rich club density was found to be associated with lower levels of global communication capacity, a relationship that was absent for other white matter pathways. In addition, patients had an increase in the strength of structural connectivity-functional connectivity coupling. Our findings provide novel biological evidence that schizophrenia is characterized by a selective

  8. Regional specificity of aberrant thalamocortical connectivity in autism.

    PubMed

    Nair, Aarti; Carper, Ruth A; Abbott, Angela E; Chen, Colleen P; Solders, Seraphina; Nakutin, Sarah; Datko, Michael C; Fishman, Inna; Müller, Ralph-Axel

    2015-11-01

    Preliminary evidence suggests aberrant (mostly reduced) thalamocortical (TC) connectivity in autism spectrum disorder (ASD), but despite the crucial role of thalamus in sensorimotor functions and its extensive connectivity with cerebral cortex, relevant evidence remains limited. We performed a comprehensive investigation of region-specific TC connectivity in ASD. Resting-state functional MRI and diffusion tensor imaging (DTI) data were acquired for 60 children and adolescents with ASD (ages 7-17 years) and 45 age, sex, and IQ-matched typically developing (TD) participants. We examined intrinsic functional connectivity (iFC) and anatomical connectivity (probabilistic tractography) with thalamus, using 68 unilateral cerebral cortical regions of interest (ROIs). For frontal and parietal lobes, iFC was atypically reduced in the ASD group for supramodal association cortices, but was increased for cingulate gyri and motor cortex. Temporal iFC was characterized by overconnectivity for auditory cortices, but underconnectivity for amygdalae. Occipital iFC was broadly reduced in the ASD group. DTI indices (such as increased radial diffusion) for regions with group differences in iFC further indicated compromised anatomical connectivity, especially for frontal ROIs, in the ASD group. Our findings highlight the regional specificity of aberrant TC connectivity in ASD. Their overall pattern can be largely accounted for by functional overconnectivity with limbic and sensorimotor regions, but underconnectivity with supramodal association cortices. This could be related to comparatively early maturation of limbic and sensorimotor regions in the context of early overgrowth in ASD, at the expense of TC connectivity with later maturing cortical regions. © 2015 Wiley Periodicals, Inc.

  9. Detection of Structural Abnormalities Using Neural Nets

    NASA Technical Reports Server (NTRS)

    Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

    1996-01-01

    This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

  10. Dynamics of human subthalamic neuron phase-locking to motor and sensory cortical oscillations during movement.

    PubMed

    Lipski, Witold J; Wozny, Thomas A; Alhourani, Ahmad; Kondylis, Efstathios D; Turner, Robert S; Crammond, Donald J; Richardson, Robert Mark

    2017-09-01

    Coupled oscillatory activity recorded between sensorimotor regions of the basal ganglia-thalamocortical loop is thought to reflect information transfer relevant to movement. A neuronal firing-rate model of basal ganglia-thalamocortical circuitry, however, has dominated thinking about basal ganglia function for the past three decades, without knowledge of the relationship between basal ganglia single neuron firing and cortical population activity during movement itself. We recorded activity from 34 subthalamic nucleus (STN) neurons, simultaneously with cortical local field potentials and motor output, in 11 subjects with Parkinson's disease (PD) undergoing awake deep brain stimulator lead placement. STN firing demonstrated phase synchronization to both low- and high-beta-frequency cortical oscillations, and to the amplitude envelope of gamma oscillations, in motor cortex. We found that during movement, the magnitude of this synchronization was dynamically modulated in a phase-frequency-specific manner. Importantly, we found that phase synchronization was not correlated with changes in neuronal firing rate. Furthermore, we found that these relationships were not exclusive to motor cortex, because STN firing also demonstrated phase synchronization to both premotor and sensory cortex. The data indicate that models of basal ganglia function ultimately will need to account for the activity of populations of STN neurons that are bound in distinct functional networks with both motor and sensory cortices and code for movement parameters independent of changes in firing rate. NEW & NOTEWORTHY Current models of basal ganglia-thalamocortical networks do not adequately explain simple motor functions, let alone dysfunction in movement disorders. Our findings provide data that inform models of human basal ganglia function by demonstrating how movement is encoded by networks of subthalamic nucleus (STN) neurons via dynamic phase synchronization with cortex. The data also

  11. Brain-state invariant thalamo-cortical coordination revealed by non-linear encoders.

    PubMed

    Viejo, Guillaume; Cortier, Thomas; Peyrache, Adrien

    2018-03-01

    Understanding how neurons cooperate to integrate sensory inputs and guide behavior is a fundamental problem in neuroscience. A large body of methods have been developed to study neuronal firing at the single cell and population levels, generally seeking interpretability as well as predictivity. However, these methods are usually confronted with the lack of ground-truth necessary to validate the approach. Here, using neuronal data from the head-direction (HD) system, we present evidence demonstrating how gradient boosted trees, a non-linear and supervised Machine Learning tool, can learn the relationship between behavioral parameters and neuronal responses with high accuracy by optimizing the information rate. Interestingly, and unlike other classes of Machine Learning methods, the intrinsic structure of the trees can be interpreted in relation to behavior (e.g. to recover the tuning curves) or to study how neurons cooperate with their peers in the network. We show how the method, unlike linear analysis, reveals that the coordination in thalamo-cortical circuits is qualitatively the same during wakefulness and sleep, indicating a brain-state independent feed-forward circuit. Machine Learning tools thus open new avenues for benchmarking model-based characterization of spike trains.

  12. Brain-state invariant thalamo-cortical coordination revealed by non-linear encoders

    PubMed Central

    Cortier, Thomas; Peyrache, Adrien

    2018-01-01

    Understanding how neurons cooperate to integrate sensory inputs and guide behavior is a fundamental problem in neuroscience. A large body of methods have been developed to study neuronal firing at the single cell and population levels, generally seeking interpretability as well as predictivity. However, these methods are usually confronted with the lack of ground-truth necessary to validate the approach. Here, using neuronal data from the head-direction (HD) system, we present evidence demonstrating how gradient boosted trees, a non-linear and supervised Machine Learning tool, can learn the relationship between behavioral parameters and neuronal responses with high accuracy by optimizing the information rate. Interestingly, and unlike other classes of Machine Learning methods, the intrinsic structure of the trees can be interpreted in relation to behavior (e.g. to recover the tuning curves) or to study how neurons cooperate with their peers in the network. We show how the method, unlike linear analysis, reveals that the coordination in thalamo-cortical circuits is qualitatively the same during wakefulness and sleep, indicating a brain-state independent feed-forward circuit. Machine Learning tools thus open new avenues for benchmarking model-based characterization of spike trains. PMID:29565979

  13. Thalamic synchrony and dynamic regulation of global forebrain oscillations.

    PubMed

    Huguenard, John R; McCormick, David A

    2007-07-01

    The circuitry within the thalamus creates an intrinsic oscillatory unit whose function depends critically on reciprocal synaptic connectivity between excitatory thalamocortical relay neurons and inhibitory thalamic reticular neurons along with a robust post-inhibitory rebound mechanism in relay neurons. Feedforward and feedback connections between cortex and thalamus reinforce the thalamic oscillatory activity into larger thalamocortical networks to generate sleep spindles and spike-wave discharge of generalized absence epilepsy. The degree of synchrony within the thalamic network seems to be crucial in determining whether normal (spindle) or pathological (spike-wave) oscillations occur, and recent studies show that regulation of excitability in the reticular nucleus leads to dynamical modulation of the state of the thalamic circuit and provide a basis for explaining how a variety of unrelated genetic alterations might lead to the spike-wave phenotype. In addition, given the central role of the reticular nucleus in generating spike-wave discharge, these studies have suggested specific interventions that would prevent seizures while still allowing normal spindle generation to occur. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

  14. Abnormal Mitochondrial Dynamics and Synaptic Degeneration as Early Events in Alzheimer’s Disease: Implications to Mitochondria-Targeted Antioxidant Therapeutics

    PubMed Central

    Reddy, P. Hemachandra; Tripathy, Raghav; Troung, Quang; Thirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala P.; Mao, Peizhong; Manczak, Maria

    2011-01-01

    Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer’s disease (AD) progression. Loss of synapses and synaptic damage are the best correlate of cognitive deficits found in AD patients. Recent research on amyloid bet (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed that reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. PMID:22037588

  15. Modeling of abnormal mechanical properties of nickel-based single crystal superalloy by three-dimensional discrete dislocation dynamics

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Li, Zhenhuan; Huang, Minsheng

    2014-12-01

    Unlike common single crystals, the nickel-based single crystal superalloy shows surprisingly anomalous flow strength (i.e. with the increase of temperature, the yield strength first increases to a peak value and then decreases) and tension-compression (TC) asymmetry. A comprehensive three-dimensional discrete dislocation dynamics (3D-DDD) procedure was developed to model these abnormal mechanical properties. For this purpose, a series of complicated dynamic evolution details of Kear-Wilsdorf (KW) locks, which are closely related to the flow strength anomaly and TC asymmetry, were incorporated into this 3D-DDD framework. Moreover, the activation of the cubic slip system, which is the origin of the decrease in yield strength with increasing temperature at relatively high temperatures, was especially taken into account by introducing a competition criterion between the unlocking of the KW locks and the activation of the cubic slip system. To test our framework, a series of 3D-DDD simulations were performed on a representative volume cell model with a cuboidal Ni3Al precipitate phase embedded in a nickel matrix. Results show that the present 3D-DDD procedure can successfully capture the dynamic evolution of KW locks, the flow strength anomaly and TC asymmetry. Then, the underlying dislocation mechanisms leading to these abnormal mechanical responses were investigated and discussed in detail. Finally, a cyclic deformation of the nickel-based single crystal superalloy was modeled by using the present DDD model, with a special focus on the influence of KW locks on the Bauschinger effect and cyclic softening.

  16. Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe

    PubMed Central

    Fiáth, Richárd; Beregszászi, Patrícia; Horváth, Domonkos; Wittner, Lucia; Aarts, Arno A. A.; Ruther, Patrick; Neves, Hercules P.; Bokor, Hajnalka; Acsády, László

    2016-01-01

    Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study. PMID:27535370

  17. Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe.

    PubMed

    Fiáth, Richárd; Beregszászi, Patrícia; Horváth, Domonkos; Wittner, Lucia; Aarts, Arno A A; Ruther, Patrick; Neves, Hercules P; Bokor, Hajnalka; Acsády, László; Ulbert, István

    2016-11-01

    Recording simultaneous activity of a large number of neurons in distributed neuronal networks is crucial to understand higher order brain functions. We demonstrate the in vivo performance of a recently developed electrophysiological recording system comprising a two-dimensional, multi-shank, high-density silicon probe with integrated complementary metal-oxide semiconductor electronics. The system implements the concept of electronic depth control (EDC), which enables the electronic selection of a limited number of recording sites on each of the probe shafts. This innovative feature of the system permits simultaneous recording of local field potentials (LFP) and single- and multiple-unit activity (SUA and MUA, respectively) from multiple brain sites with high quality and without the actual physical movement of the probe. To evaluate the in vivo recording capabilities of the EDC probe, we recorded LFP, MUA, and SUA in acute experiments from cortical and thalamic brain areas of anesthetized rats and mice. The advantages of large-scale recording with the EDC probe are illustrated by investigating the spatiotemporal dynamics of pharmacologically induced thalamocortical slow-wave activity in rats and by the two-dimensional tonotopic mapping of the auditory thalamus. In mice, spatial distribution of thalamic responses to optogenetic stimulation of the neocortex was examined. Utilizing the benefits of the EDC system may result in a higher yield of useful data from a single experiment compared with traditional passive multielectrode arrays, and thus in the reduction of animals needed for a research study. Copyright © 2016 the American Physiological Society.

  18. Mapping remodeling of thalamocortical projections in the living reeler mouse brain by diffusion tractography

    PubMed Central

    Harsan, Laura-Adela; Dávid, Csaba; Reisert, Marco; Schnell, Susanne; Hennig, Jürgen; von Elverfeldt, Dominik; Staiger, Jochen F.

    2013-01-01

    A major challenge in neuroscience is to accurately decipher in vivo the entire brain circuitry (connectome) at a microscopic level. Currently, the only methodology providing a global noninvasive window into structural brain connectivity is diffusion tractography. The extent to which the reconstructed pathways reflect realistic neuronal networks depends, however, on data acquisition and postprocessing factors. Through a unique combination of approaches, we designed and evaluated herein a framework for reliable fiber tracking and mapping of the living mouse brain connectome. One important wiring scheme, connecting gray matter regions and passing fiber-crossing areas, was closely examined: the lemniscal thalamocortical (TC) pathway. We quantitatively validated the TC projections inferred from in vivo tractography with correlative histological axonal tracing in the same wild-type and reeler mutant mice. We demonstrated noninvasively that changes in patterning of the cortical sheet, such as highly disorganized cortical lamination in reeler, led to spectacular compensatory remodeling of the TC pathway. PMID:23610438

  19. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.

    PubMed

    Damaraju, E; Allen, E A; Belger, A; Ford, J M; McEwen, S; Mathalon, D H; Mueller, B A; Pearlson, G D; Potkin, S G; Preda, A; Turner, J A; Vaidya, J G; van Erp, T G; Calhoun, V D

    2014-01-01

    Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group

  20. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

    PubMed Central

    Damaraju, E.; Allen, E.A.; Belger, A.; Ford, J.M.; McEwen, S.; Mathalon, D.H.; Mueller, B.A.; Pearlson, G.D.; Potkin, S.G.; Preda, A.; Turner, J.A.; Vaidya, J.G.; van Erp, T.G.; Calhoun, V.D.

    2014-01-01

    Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical–subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group

  1. ALS-associated mutation SOD1G93A leads to abnormal mitochondrial dynamics in osteocytes.

    PubMed

    Wang, Huan; Yi, Jianxun; Li, Xuejun; Xiao, Yajuan; Dhakal, Kamal; Zhou, Jingsong

    2018-01-01

    While the death of motor neuron is a pathological hallmark of amyotrophic lateral sclerosis (ALS), defects in other cell types or organs may also actively contribute to ALS disease progression. ALS patients experience progressive skeletal muscle wasting that may not only exacerbate neuronal degeneration, but likely has a significant impact on bone function. In our previous published study, we have discovered severe bone loss in an ALS mouse model with overexpression of ALS-associated mutation SOD1 G93A (G93A). Here we further provide a mechanistic understanding of the bone loss in ALS animal and cellular models. Combining mitochondrial fluorescent indicators and confocal live cell imaging, we discovered abnormalities in mitochondrial network and dynamics in primary osteocytes derived from the same ALS mouse model G93A. Those mitochondrial defects occur in ALS mice after the onset of neuromuscular symptoms, indicating that mitochondria in bone cells respond to muscle atrophy during ALS disease progression. To examine whether ALS mutation has a direct contribution to mitochondrial dysfunction independent of muscle atrophy, we evaluated mitochondrial morphology and motility in cultured osteocytes (MLO-Y4) with overexpression of mitochondrial targeted SOD1 G93A . Compared with osteocytes overexpressing the wild type SOD1 as a control, the SOD1 G93A osteocytes showed similar defects in mitochondrial network and dynamic as that of the primary osteocytes derived from the ALS mouse model. In addition, we further discovered that overexpression of SOD1 G93A enhanced the expression level of dynamin-related protein 1 (Drp1), a key protein promoting mitochondrial fission activity, and reduced the expression level of optic atrophy protein 1 (OPA1), a key protein related to mitochondrial fusion. A specific mitochondrial fission inhibitor (Mdivi-1) partially reversed the effect of SOD1 G93A on mitochondrial network and dynamics, indicating that SOD1 G93A likely promotes

  2. Lhx2 Expression in Postmitotic Cortical Neurons Initiates Assembly of the Thalamocortical Somatosensory Circuit.

    PubMed

    Wang, Chia-Fang; Hsing, Hsiang-Wei; Zhuang, Zi-Hui; Wen, Meng-Hsuan; Chang, Wei-Jen; Briz, Carlos G; Nieto, Marta; Shyu, Bai Chuang; Chou, Shen-Ju

    2017-01-24

    Cortical neurons must be specified and make the correct connections during development. Here, we examine a mechanism initiating neuronal circuit formation in the barrel cortex, a circuit comprising thalamocortical axons (TCAs) and layer 4 (L4) neurons. When Lhx2 is selectively deleted in postmitotic cortical neurons using conditional knockout (cKO) mice, L4 neurons in the barrel cortex are initially specified but fail to form cellular barrels or develop polarized dendrites. In Lhx2 cKO mice, TCAs from the thalamic ventral posterior nucleus reach the barrel cortex but fail to further arborize to form barrels. Several activity-regulated genes and genes involved in regulating barrel formation are downregulated in the Lhx2 cKO somatosensory cortex. Among them, Btbd3, an activity-regulated gene controlling dendritic development, is a direct downstream target of Lhx2. We find that Lhx2 confers neuronal competency for activity-dependent dendritic development in L4 neurons by inducing the expression of Btbd3. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Beyond static measures: A review of functional magnetic resonance spectroscopy and its potential to investigate dynamic glutamatergic abnormalities in schizophrenia.

    PubMed

    Jelen, Luke A; King, Sinead; Mullins, Paul G; Stone, James M

    2018-05-01

    Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy ( 1 H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1 H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.

  4. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  5. Central Nervous System-Toxic Lidocaine Concentrations Unmask L-Type Ca²⁺ Current-Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study.

    PubMed

    Putrenko, Igor; Ghavanini, Amer A; Meyer Schöniger, Katrin S; Schwarz, Stephan K W

    2016-05-01

    High systemic lidocaine concentrations exert well-known toxic effects on the central nervous system (CNS), including seizures, coma, and death. The underlying mechanisms are still largely obscure, and the actions of lidocaine on supraspinal neurons have received comparatively little study. We recently found that lidocaine at clinically neurotoxic concentrations increases excitability mediated by Na-independent, high-threshold (HT) action potential spikes in rat thalamocortical neurons. Our goal in this study was to characterize these spikes and test the hypothesis that they are generated by HT Ca currents, previously implicated in neurotoxicity. We also sought to identify and isolate the specific underlying subtype of Ca current. We investigated the actions of lidocaine in the CNS-toxic concentration range (100 μM-1 mM) on ventrobasal thalamocortical neurons in rat brain slices in vitro, using whole-cell patch-clamp recordings aided by differential interference contrast infrared videomicroscopy. Drugs were bath applied; action potentials were generated using current clamp protocols, and underlying currents were identified and isolated with ion channel blockers and electrolyte substitution. Lidocaine (100 μM-1 mM) abolished Na-dependent tonic firing in all neurons tested (n = 46). However, in 39 of 46 (85%) neurons, lidocaine unmasked evoked HT action potentials with lower amplitudes and rates of de-/repolarization compared with control. These HT action potentials remained during the application of tetrodotoxin (600 nM), were blocked by Cd (50 μM), and disappeared after superfusion with an extracellular solution deprived of Ca. These features implied that the unmasked potentials were generated by high-voltage-activated Ca channels and not by Na channels. Application of the L-type Ca channel blocker, nifedipine (5 μM), completely blocked the HT potentials, whereas the N-type Ca channel blocker, ω-conotoxin GVIA (1 μM), had little effect. At clinically CNS

  6. Exercising upper respiratory videoendoscopic evaluation of 100 nonracing performance horses with abnormal respiratory noise and/or poor performance.

    PubMed

    Davidson, E J; Martin, B B; Boston, R C; Parente, E J

    2011-01-01

    Although well documented in racehorses, there is paucity in the literature regarding the prevalence of dynamic upper airway abnormalities in nonracing performance horses. To describe upper airway function of nonracing performance horses with abnormal respiratory noise and/or poor performance via exercising upper airway videoendoscopy. Medical records of nonracing performance horses admitted for exercising evaluation with a chief complaint of abnormal respiratory noise and/or poor performance were reviewed. All horses had video recordings of resting and exercising upper airway endoscopy. Relationships between horse demographics, resting endoscopic findings, treadmill intensity and implementation of head and neck flexion during exercise with exercising endoscopic findings were examined. Dynamic upper airway obstructions were observed in 72% of examinations. Head and neck flexion was necessary to obtain a diagnosis in 21 horses. Pharyngeal wall collapse was the most prevalent upper airway abnormality, observed in 31% of the examinations. Complex abnormalities were noted in 27% of the examinations. Resting laryngeal dysfunction was significantly associated with dynamic arytenoid collapse and the odds of detecting intermittent dorsal displacement of the soft palate (DDSP) during exercise in horses with resting DDSP was only 7.7%. Exercising endoscopic observations were different from the resting observations in 54% of examinations. Dynamic upper airway obstructions were common in nonracing performance horses with respiratory noise and/or poor performance. Resting endoscopy was only helpful in determining exercising abnormalities with recurrent laryngeal neuropathy. This study emphasises the importance of exercising endoscopic evaluation in nonracing performance horses with abnormal respiratory noise and/or poor performance for accurate assessment of dynamic upper airway function. © 2010 EVJ Ltd.

  7. Quantifying the abnormal hemodynamics of sickle cell anemia

    NASA Astrophysics Data System (ADS)

    Lei, Huan; Karniadakis, George

    2012-02-01

    Sickle red blood cells (SS-RBC) exhibit heterogeneous morphologies and abnormal hemodynamics in deoxygenated states. A multi-scale model for SS-RBC is developed based on the Dissipative Particle Dynamics (DPD) method. Different cell morphologies (sickle, granular, elongated shapes) typically observed in deoxygenated states are constructed and quantified by the Asphericity and Elliptical shape factors. The hemodynamics of SS-RBC suspensions is studied in both shear and pipe flow systems. The flow resistance obtained from both systems exhibits a larger value than the healthy blood flow due to the abnormal cell properties. Moreover, SS-RBCs exhibit abnormal adhesive interactions with both the vessel endothelium cells and the leukocytes. The effect of the abnormal adhesive interactions on the hemodynamics of sickle blood is investigated using the current model. It is found that both the SS-RBC - endothelium and the SS-RBC - leukocytes interactions, can potentially trigger the vicious ``sickling and entrapment'' cycles, resulting in vaso-occlusion phenomena widely observed in micro-circulation experiments.

  8. Thalamocortical integration of instrumental learning and performance and their disintegration in addiction.

    PubMed

    Balleine, Bernard W; Morris, Richard W; Leung, Beatrice K

    2015-12-02

    A recent focus of addiction research has been on the effect of drug exposure on the neural processes that mediate the acquisition and performance of goal-directed instrumental actions. Deficits in goal-directed control and a consequent dysregulation of habit learning processes have been described as resulting in compulsive drug seeking. Similarly, considerable research has focussed on the motivational and emotional changes that drugs produce and that result in changes in the incentive processes that modulate goal-directed performance. Although these areas have developed independently, we argue that the effects they described are likely not independent. Here we hypothesize that these changes result from a core deficit in the way the learning and performance factors that support goal-directed action are integrated at a neural level to maintain behavioural control. A dorsal basal ganglia stream mediating goal-directed learning and a ventral stream mediating various performance factors find several points of integration in the cortical basal ganglia system, most notably in the thalamocortical network linking basal ganglia output to a variety of cortical control centres. Recent research in humans and other animals is reviewed suggesting that learning and performance factors are integrated in a network centred on the mediodorsal thalamus and that disintegration in this network may provide the basis for a 'switch' from recreational to dysregulated drug seeking resulting in the well documented changes associated with addiction. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Slits are chemorepellents endogenous to hypothalamus and steer thalamocortical axons into ventral telencephalon.

    PubMed

    Braisted, Janet E; Ringstedt, Thomas; O'Leary, Dennis D M

    2009-07-01

    Thalamocortical axons (TCAs) originate in dorsal thalamus, extend ventrally along the lateral thalamic surface, and as they approach hypothalamus make a lateral turn into ventral telencephalon. In vitro studies show that hypothalamus releases a chemorepellent for TCAs, and analyses of knockout mice indicate that Slit chemorepellents and their receptor Robo2 influence TCA pathfinding. We show that Slit chemorepellents are the hypothalamic chemorepellent and act through Robos to steer TCAs into ventral telencephalon. During TCA pathfinding, Slit1 and Slit2 are expressed in hypothalamus and ventral thalamus and Robo1 and Robo2 are expressed in dorsal thalamus. In collagen gel cocultures of dorsal thalamus and Slit2-expressing cells, axon number and length are decreased on the explant side facing Slit2-expressing cells, overall axon outgrowth is diminished, and axons turn away from the Slit2-expressing cells. Thus, Slit2 is an inhibitor and chemorepellent for dorsal thalamic axons. Collagen gel cocultures of dorsal thalamus with sections of live diencephalon, with and without the hypothalamus portion overlaid with Robo2-fc-expressing cells to block Slit function, identify Slits as the hypothalamic chemorepellent. Thus, Slits are chemorepellents for TCAs endogenous to hypothalamus and steer TCAs from diencephalon into ventral telencephalon, a critical pathfinding event defective in Slit and Robo2 mutant mice.

  10. The Thalamocortical Projection Systems in Primate: An Anatomical Support for Multisensory and Sensorimotor Interplay

    PubMed Central

    Cappe, Céline; Morel, Anne; Barone, Pascal

    2009-01-01

    Multisensory and sensorimotor integrations are usually considered to occur in superior colliculus and cerebral cortex, but few studies proposed the thalamus as being involved in these integrative processes. We investigated whether the organization of the thalamocortical (TC) systems for different modalities partly overlap, representing an anatomical support for multisensory and sensorimotor interplay in thalamus. In 2 macaque monkeys, 6 neuroanatomical tracers were injected in the rostral and caudal auditory cortex, posterior parietal cortex (PE/PEa in area 5), and dorsal and ventral premotor cortical areas (PMd, PMv), demonstrating the existence of overlapping territories of thalamic projections to areas of different modalities (sensory and motor). TC projections, distinct from the ones arising from specific unimodal sensory nuclei, were observed from motor thalamus to PE/PEa or auditory cortex and from sensory thalamus to PMd/PMv. The central lateral nucleus and the mediodorsal nucleus project to all injected areas, but the most significant overlap across modalities was found in the medial pulvinar nucleus. The present results demonstrate the presence of thalamic territories integrating different sensory modalities with motor attributes. Based on the divergent/convergent pattern of TC and corticothalamic projections, 4 distinct mechanisms of multisensory and sensorimotor interplay are proposed. PMID:19150924

  11. Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

    PubMed Central

    Wagener, Robin J.; Witte, Mirko; Guy, Julien; Mingo-Moreno, Nieves; Kügler, Sebastian; Staiger, Jochen F.

    2016-01-01

    Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory “barrel” cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position. PMID:26564256

  12. Abnormal functional integration of thalamic low frequency oscillation in the BOLD signal after acute heroin treatment.

    PubMed

    Denier, Niklaus; Schmidt, André; Gerber, Hana; Vogel, Marc; Huber, Christian G; Lang, Undine E; Riecher-Rossler, Anita; Wiesbeck, Gerhard A; Radue, Ernst-Wilhelm; Walter, Marc; Borgwardt, Stefan

    2015-12-01

    Heroin addiction is a severe relapsing brain disorder associated with impaired cognitive control, including deficits in attention allocation. The thalamus has a high density of opiate receptors and is critically involved in orchestrating cortical activity during cognitive control. However, there have been no studies on how acute heroin treatment modulates thalamic activity. In a cross-over, double-blind, vehicle-controlled study, 29 heroin-maintained outpatients were studied after heroin and placebo administration, while 20 healthy controls were included for the placebo condition only. Resting-state functional magnetic resonance imaging was used to analyze functional integration of the thalamus by three different resting state analysis techniques. Thalamocortical functional connectivity (FC) was analyzed by seed-based correlation, while intrinsic thalamic oscillation was assessed by analysis of regional homogeneity (ReHo) and the fractional amplitude of low frequency fluctuations (fALFF). Relative to the placebo treatment and healthy controls, acute heroin administration reduced thalamocortical FC to cortical regions, including the frontal cortex, while the reductions in FC to the mediofrontal cortex, orbitofrontal cortex, and frontal pole were positively correlated with the plasma level of morphine, the main psychoactive metabolite of heroin. Furthermore, heroin treatment was associated with increased thalamic ReHo and fALFF values, whereas fALFF following heroin exposure correlated negatively with scores of attentional control. The heroin-associated increase in fALFF was mainly dominated by slow-4 (0.027-0.073 Hz) oscillations. Our findings show that there are acute effects of heroin within the thalamocortical system and may shed new light on the role of the thalamus in cognitive control in heroin addiction. Future research is needed to determine the underlying physiological mechanisms and their role in heroin addiction. © 2015 Wiley Periodicals, Inc.

  13. Localized Hotspots Drive Continental Geography of Abnormal Amphibians on U.S. Wildlife Refuges

    PubMed Central

    Reeves, Mari K.; Medley, Kimberly A.; Pinkney, Alfred E.; Holyoak, Marcel; Johnson, Pieter T. J.; Lannoo, Michael J.

    2013-01-01

    Amphibians with missing, misshapen, and extra limbs have garnered public and scientific attention for two decades, yet the extent of the phenomenon remains poorly understood. Despite progress in identifying the causes of abnormalities in some regions, a lack of knowledge about their broader spatial distribution and temporal dynamics has hindered efforts to understand their implications for amphibian population declines and environmental quality. To address this data gap, we conducted a nationwide, 10-year assessment of 62,947 amphibians on U.S. National Wildlife Refuges. Analysis of a core dataset of 48,081 individuals revealed that consistent with expected background frequencies, an average of 2% were abnormal, but abnormalities exhibited marked spatial variation with a maximum prevalence of 40%. Variance partitioning analysis demonstrated that factors associated with space (rather than species or year sampled) captured 97% of the variation in abnormalities, and the amount of partitioned variance decreased with increasing spatial scale (from site to refuge to region). Consistent with this, abnormalities occurred in local to regional hotspots, clustering at scales of tens to hundreds of kilometers. We detected such hotspot clusters of high-abnormality sites in the Mississippi River Valley, California, and Alaska. Abnormality frequency was more variable within than outside of hotspot clusters. This is consistent with dynamic phenomena such as disturbance or natural enemies (pathogens or predators), whereas similarity of abnormality frequencies at scales of tens to hundreds of kilometers suggests involvement of factors that are spatially consistent at a regional scale. Our characterization of the spatial and temporal variation inherent in continent-wide amphibian abnormalities demonstrates the disproportionate contribution of local factors in predicting hotspots, and the episodic nature of their occurrence. PMID:24260103

  14. A role for the preoptic sleep-promoting system in absence epilepsy.

    PubMed

    Suntsova, N; Kumar, S; Guzman-Marin, R; Alam, M N; Szymusiak, R; McGinty, D

    2009-10-01

    Absence epilepsy (AE) in humans and the genetic AE model in WAG/Rij rats are both associated with abnormalities in sleep architecture that suggest insufficiency of the sleep-promoting mechanisms. In this study we compared the functionality of sleep-active neuronal groups within two well-established sleep-promoting sites, the ventrolateral and median preoptic nuclei (VLPO and MnPN, respectively), in WAG/Rij and control rats. Neuronal activity was assessed using c-Fos immunoreactivity and chronic single-unit recording techniques. We found that WAG/Rij rats exhibited a lack of sleep-associated c-Fos activation of GABAergic MnPN and VLPO neurons, a lower percentage of MnPN and VLPO cells increasing discharge during sleep and reduced firing rates of MnPN sleep-active neurons, compared to non-epileptic rats. The role of sleep-promoting mechanisms in pathogenesis of absence seizures was assessed in non-epileptic rats using electrical stimulation and chemical manipulations restricted to the MnPN. We found that fractional activation of the sleep-promoting system in waking was sufficient to elicit absence-like seizures. Given that reciprocally interrelated sleep-promoting and arousal neuronal groups control thalamocortical excitability, we hypothesize that malfunctioning of sleep-promoting system results in impaired ascending control over thalamocortical rhythmogenic mechanisms during wake-sleep transitions thus favoring aberrant thalamocortical oscillations. Our findings suggest a pathological basis for AE-associated sleep abnormalities and a mechanism underlying association of absence seizures with wake-sleep transitions.

  15. Control of Abnormal Synchronization in Neurological Disorders

    PubMed Central

    Popovych, Oleksandr V.; Tass, Peter A.

    2014-01-01

    In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

  16. Abnormal electrocardiographic findings in athletes: Correlation with intensity of sport and level of competition.

    PubMed

    Dores, Hélder; Malhotra, Aneil; Sheikh, Nabeel; Millar, Lynne; Dhutia, Harshil; Narain, Rajay; Merghani, Ahmed; Papadakis, Michael; Sharma, Sanjay

    2016-11-01

    Athletes can exhibit abnormal electrocardiogram (ECG) phenotypes that require further evaluation prior to competition. These are apparently more prevalent in high-intensity endurance sports. The purpose of this study was to assess the association between ECG findings in athletes and intensity of sport and level of competition. A cohort of 3423 competitive athletes had their ECGs assessed according to the Seattle criteria (SC). The presence of abnormal ECGs was correlated with: (1) intensity of sport (low/moderate vs. at least one high static or dynamic component); (2) competitive level (regional vs. national/international); (3) training volume (≤20 vs. >20 hours/week); (4) type of sport (high dynamic vs. high static component). The same endpoints were studied according to the 'Refined Criteria' (RC). Abnormal ECGs according to the SC were present in 225 (6.6%) athletes, more frequently in those involved in high-intensity sports (8.0% vs. 5.4%; p=0.002), particularly in dynamic sports, and competing at national/international level (7.1% vs. 4.9%; p=0.028). Training volume was not significantly associated with abnormal ECGs. By multivariate analysis, high-intensity sport (OR 1.55, 1.18-2.03; p=0.002) and national/international level (OR 1.50, 95% CI 1.04-2.14; p=0.027) were independent predictors of abnormal ECGs, and these variables, when combined, doubled the prevalence of this finding. According to the RC, abnormal ECGs decreased to 103 (3.0%), but were also more frequent in high-intensity sports (4.2% vs. 2.0%; p<0.001). There is a positive correlation between higher intensity of sports and increased prevalence of ECG abnormalities. This relationship persists with the use of more restrictive criteria for ECG interpretation, although the number of abnormal ECGs is lower. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Melatonin prevents abnormal mitochondrial dynamics resulting from the neurotoxicity of cadmium by blocking calcium-dependent translocation of Drp1 to the mitochondria.

    PubMed

    Xu, Shangcheng; Pi, Huifeng; Zhang, Lei; Zhang, Nixian; Li, YuMing; Zhang, Huiliang; Tang, Ju; Li, Huijuan; Feng, Min; Deng, Ping; Guo, Pan; Tian, Li; Xie, Jia; He, Mindi; Lu, Yonghui; Zhong, Min; Zhang, Yanwen; Wang, Wang; Reiter, Russel J; Yu, Zhengping; Zhou, Zhou

    2016-04-01

    Cadmium (Cd) is a persistent environmental toxin and occupational pollutant that is considered to be a potential risk factor in the development of neurodegenerative diseases. Abnormal mitochondrial dynamics are increasingly implicated in mitochondrial damage in various neurological pathologies. The aim of this study was to investigate whether the disturbance of mitochondrial dynamics contributed to Cd-induced neurotoxicity and whether melatonin has any neuroprotective properties. After cortical neurons were exposed to 10 μM cadmium chloride (CdCl2 ) for various periods (0, 3, 6, 12, and 24 hr), the morphology of their mitochondria significantly changed from the normal tubular networks into punctuated structures within 3 hr. Following this pronounced mitochondrial fragmentation, Cd treatment led to signs of mitochondrial dysfunction, including excess reactive oxygen species (ROS) production, decreased ATP content, and mitochondrial membrane potential (▵Ψm) loss. However, 1 mM melatonin pretreatment efficiently attenuated the Cd-induced mitochondrial fragmentation, which improved the turnover of mitochondrial function. In the brain tissues of rats that were intraperitoneally given 1 mg/kg CdCl2 for 7 days, melatonin also ameliorated excessive mitochondrial fragmentation and mitochondrial damage in vivo. Melatonin's protective effects were attributed to its roles in preventing cytosolic calcium ([Ca(2+) ]i ) overload, which blocked the recruitment of Drp1 from the cytoplasm to the mitochondria. Taken together, our results are the first to demonstrate that abnormal mitochondrial dynamics is involved in cadmium-induced neurotoxicity. Melatonin has significant pharmacological potential in protecting against the neurotoxicity of Cd by blocking the disbalance of mitochondrial fusion and fission. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

    PubMed

    Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

    2015-11-01

    The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the

  19. Mixed Pattern Matching-Based Traffic Abnormal Behavior Recognition

    PubMed Central

    Cui, Zhiming; Zhao, Pengpeng

    2014-01-01

    A motion trajectory is an intuitive representation form in time-space domain for a micromotion behavior of moving target. Trajectory analysis is an important approach to recognize abnormal behaviors of moving targets. Against the complexity of vehicle trajectories, this paper first proposed a trajectory pattern learning method based on dynamic time warping (DTW) and spectral clustering. It introduced the DTW distance to measure the distances between vehicle trajectories and determined the number of clusters automatically by a spectral clustering algorithm based on the distance matrix. Then, it clusters sample data points into different clusters. After the spatial patterns and direction patterns learned from the clusters, a recognition method for detecting vehicle abnormal behaviors based on mixed pattern matching was proposed. The experimental results show that the proposed technical scheme can recognize main types of traffic abnormal behaviors effectively and has good robustness. The real-world application verified its feasibility and the validity. PMID:24605045

  20. Thalamocortical neuron loss and localized astrocytosis in the Cln3Deltaex7/8 knock-in mouse model of Batten disease.

    PubMed

    Pontikis, Charlie C; Cotman, Susan L; MacDonald, Marcy E; Cooper, Jonathan D

    2005-12-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is the result of mutations in the Cln3 gene. The Cln3 knock-in mouse (Cln3Deltaex7/8) reproduces the most common Cln3 mutation and we have now characterized the CNS of these mice at 12 months of age. With the exception of the thalamus, Cln3Deltaex7/8 homozygotes displayed no significant regional atrophy, but a range of changes in individual laminar thickness that resulted in variable cortical thinning across subfields. Stereological analysis revealed a pronounced loss of neurons within individual laminae of somatosensory cortex of affected mice and the novel finding of a loss of sensory relay thalamic neurons. These affected mice also exhibited profound astrocytic reactions that were most pronounced in the neocortex and thalamus, but diminished in other brain regions. These data provide the first direct evidence for neurodegenerative and reactive changes in the thalamocortical system in JNCL and emphasize the localized nature of these events.

  1. rTMS with Motor Training Modulates Cortico-Basal Ganglia-Thalamocortical Circuits in Stroke Patients

    PubMed Central

    Chang, Won Hyuk; Kim, Yun-Hee; Yoo, Woo-Kyoung; Goo, Kyoung-Hyup; Park, Chang-hyun; Kim, Sung Tae; Pascual-Leone, Alvaro

    2013-01-01

    Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) may enhance plastic changes in the human cortex and modulation of behavior. However, the underlying neural mechanisms have not been sufficiently investigated. We examined the clinical effects and neural correlates of high-frequency rTMS coupled with motor training in patients with hemiparesis after stroke. Methods Twenty-one patients were randomly divided into two groups, and received either real or sham rTMS. Ten daily sessions of 1,000 pulses of real or sham rTMS were applied at 10 Hz over the primary motor cortex of the affected hemisphere, coupled with sequential finger motor training of the paretic hand. Functional MRIs were obtained before and after training using sequential finger motor tasks, and performances were assessed. Results Following rTMS intervention, movement accuracy of sequential finger motor tasks showed significantly greater improvement in the real group than in the sham group (p<0.05). Real rTMS modulated areas of brain activation during performance of motor tasks with a significant interaction effect in the sensorimotor cortex, thalamus, and caudate nucleus. Patients in the real rTMS group also showed significantly enhanced activation in the affected hemisphere compared to the sham rTMS group. Conclusion According to these results, a 10 day course of high-frequency rTMS coupled with motor training improved motor performance through modulation of activities in the cortico-basal ganglia-thalamocortical circuits. PMID:22555430

  2. 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.…

  3. 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 ...

  4. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

    PubMed

    Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

    2017-05-24

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

  5. The thalamic low-threshold Ca2+ potential: a key determinant of the local and global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical networks

    PubMed Central

    Crunelli, Vincenzo; Errington, Adam C.; Hughes, Stuart W.; Tóth, Tibor I.

    2011-01-01

    During non-rapid eye movement sleep and certain types of anaesthesia, neurons in the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that consists of alternating UP and DOWN membrane potential states and which correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram. While several studies have claimed that the slow oscillation is generated exclusively in neocortical networks and then transmitted to other brain areas, substantial evidence exists to suggest that the full expression of the slow oscillation in an intact thalamocortical (TC) network requires the balanced interaction of oscillator systems in both the neocortex and thalamus. Within such a scenario, we have previously argued that the powerful low-threshold Ca2+ potential (LTCP)-mediated burst of action potentials that initiates the UP states in individual TC neurons may be a vital signal for instigating UP states in related cortical areas. To investigate these issues we constructed a computational model of the TC network which encompasses the important known aspects of the slow oscillation that have been garnered from earlier in vivo and in vitro experiments. Using this model we confirm that the overall expression of the slow oscillation is intricately reliant on intact connections between the thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP-mediated bursts in TC neurons are proficient in triggering synchronous UP states in cortical networks, thereby bringing about a synchronous slow oscillation in the whole network. The importance of LTCP-mediated action potential bursts in the slow oscillation is also underlined by the observation that their associated dendritic Ca2+ signals are the only ones that inform corticothalamic synapses of the TC neuron output, since they, but not those elicited by tonic action potential firing, reach the distal dendritic sites where these synapses are located. PMID:21893530

  6. Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons.

    PubMed

    Béhuret, Sébastien; Deleuze, Charlotte; Bal, Thierry

    2015-01-01

    A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-)correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus.

  7. Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons

    PubMed Central

    Béhuret, Sébastien; Deleuze, Charlotte; Bal, Thierry

    2015-01-01

    A reason why the thalamus is more than a passive gateway for sensory signals is that two-third of the synapses of thalamocortical neurons are directly or indirectly related to the activity of corticothalamic axons. While the responses of thalamocortical neurons evoked by sensory stimuli are well characterized, with ON- and OFF-center receptive field structures, the prevalence of synaptic noise resulting from neocortical feedback in intracellularly recorded thalamocortical neurons in vivo has attracted little attention. However, in vitro and modeling experiments point to its critical role for the integration of sensory signals. Here we combine our recent findings in a unified framework suggesting the hypothesis that corticothalamic synaptic activity is adapted to modulate the transfer efficiency of thalamocortical neurons during selective attention at three different levels: First, on ionic channels by interacting with intrinsic membrane properties, second at the neuron level by impacting on the input-output gain, and third even more effectively at the cell assembly level by boosting the information transfer of sensory features encoded in thalamic subnetworks. This top-down population control is achieved by tuning the correlations in subthreshold membrane potential fluctuations and is adapted to modulate the transfer of sensory features encoded by assemblies of thalamocortical relay neurons. We thus propose that cortically-controlled (de-)correlation of subthreshold noise is an efficient and swift dynamic mechanism for selective attention in the thalamus. PMID:26733818

  8. A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals and somata.

    PubMed

    Oda, Satoko; Funato, Hiromasa; Sato, Fumi; Adachi-Akahane, Satomi; Ito, Masanori; Takase, Kenkichi; Kuroda, Masaru

    2014-06-15

    Vesicular glutamate transporter isoforms, VGluT1-VGluT3, accumulate glutamate into synaptic vesicles and are considered to be important molecules in glutamatergic transmission. Among them, VGluT2 mRNA is expressed predominantly throughout the dorsal thalamus, whereas VGluT1 mRNA is expressed in a few thalamic nuclei. In the thalamic nuclei that project to the retrosplenial cortex (RSC), VGluT1 mRNA is expressed strongly in the anterodorsal thalamic nucleus (AD), is expressed moderately in the anteroventral and laterodorsal thalamic nuclei, and is not expressed in the anteromedial thalamic nucleus. Thus, it has been strongly suggested that a subset of thalamocortical projections to RSC possesses both VGluT1 and VGluT2. In this study, double-labeled neuronal somata showing both VGluT1 and VGluT2 immunolabelings were found exclusively in the ventral region of AD (vAD). Many double-labeled axon terminals were also found in two major targets of vAD, the rostral part of the reticular thalamic nucleus and layers Ia and III-IV of the retrosplenial granular b cortex (RSGb). Some were also found in layer Ia of the retrosplenial granular a cortex (RSGa). These axon terminals contain significant amounts of both VGluTs. Because the subset of thalamocortical projections to RSC has a unique molecular basis in the glutamatergic transmission system, it might play an important role in the higher cognitive functions processed in the RSC. Furthermore, double-labeled axon terminals of a different type were distributed in RSGb and RSGa. Because they are small and the immunoreactivity of VGluT2 is significantly weaker than that of VGluT1, they seemed to be a subset of corticocortical terminals. Copyright © 2013 Wiley Periodicals, Inc.

  9. Convergent evidence for abnormal striatal synaptic plasticity in dystonia

    PubMed Central

    Peterson, David A.; Sejnowski, Terrence J.; Poizner, Howard

    2010-01-01

    Dystonia is a functionally disabling movement disorder characterized by abnormal movements and postures. Although substantial recent progress has been made in identifying genetic factors, the pathophysiology of the disease remains a mystery. A provocative suggestion gaining broader acceptance is that some aspect of neural plasticity may be abnormal. There is also evidence that, at least in some forms of dystonia, sensorimotor “use” may be a contributing factor. Most empirical evidence of abnormal plasticity in dystonia comes from measures of sensorimotor cortical organization and physiology. However, the basal ganglia also play a critical role in sensorimotor function. Furthermore, the basal ganglia are prominently implicated in traditional models of dystonia, are the primary targets of stereotactic neurosurgical interventions, and provide a neural substrate for sensorimotor learning influenced by neuromodulators. Our working hypothesis is that abnormal plasticity in the basal ganglia is a critical link between the etiology and pathophysiology of dystonia. In this review we set up the background for this hypothesis by integrating a large body of disparate indirect evidence that dystonia may involve abnormalities in synaptic plasticity in the striatum. After reviewing evidence implicating the striatum in dystonia, we focus on the influence of two neuromodulatory systems: dopamine and acetylcholine. For both of these neuromodulators, we first describe the evidence for abnormalities in dystonia and then the means by which it may influence striatal synaptic plasticity. Collectively, the evidence suggests that many different forms of dystonia may involve abnormal plasticity in the striatum. An improved understanding of these altered plastic processes would help inform our understanding of the pathophysiology of dystonia, and, given the role of the striatum in sensorimotor learning, provide a principled basis for designing therapies aimed at the dynamic processes

  10. 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.

  11. Anterograde and retrograde tracing with high molecular weight biotinylated dextran amine through thalamocortical and corticothalamic pathways.

    PubMed

    Zhang, Wenjie; Xu, Dongsheng; Cui, Jingjing; Jing, Xianghong; Xu, Nenggui; Liu, Jianhua; Bai, Wanzhu

    2017-02-01

    Biotinylated dextran amine (BDA) has been used for neural pathway tracing in the central nervous system for many decades, in which high molecular weight BDA appeared to be transported predominantly in the anterograde direction and less in the retrograde direction. In the current study, we reexamined the properties of neural labeling with high molecular weight BDA through a reciprocal neural pathway between thalamus and somatosensory cortex. After injection of BDA into the ventral posteromedial nucleus of thalamus (VPM) in the rat, the BDA labeling was sequentially examined on somatosensory cortex at 3, 5, 7, 10, and 14 survival days. Both of anterogradely labeled axonal terminals and retrogradely labeled neuronal cell bodies were observed simultaneously on the somatosensory cortex. With the increasing of survival times after injection, morphological changes occurred on the labeled axonal arbors and neuronal dendrites, in which the high quality of BDA labeling appeared on the tenth survival day. These results indicate that high molecular weight BDA is not only a sensitive anterograde tracer but also an excellent retrograde marker to be used for tracing through thalamocortical and corticothalamic pathways. And the detailed structure of neural labeling with BDA similar to Golgi-like resolution can be obtained at optimal survival times of animals after the injection of high molecular weight BDA. © 2016 Wiley Periodicals, Inc.

  12. 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.

  13. COMPARISON OF REAL-TIME MICROVASCULAR ABNORMALITIES IN PEDIATRIC AND ADULT SICKLE CELL ANEMIA PATIENTS

    PubMed Central

    Cheung, Anthony T.W.; Miller, Joshua W.; Craig, Sarah M.; To, Patricia L.; Lin, Xin; Samarron, Sandra L.; Chen, Peter C.Y.; Zwerdling, Theodore; Wun, Ted; Li, Chin-Shang; Green, Ralph

    2010-01-01

    The conjunctival microcirculation in 14 pediatric and 8 adult sickle cell anemia (SCA) patients was studied using computer-assisted intravital microscopy. The bulbar conjunctiva in SCA patients in both age groups exhibited a blanched/avascular appearance characterized by decreased vascularity. SCA patients from both age groups had many of the same abnormal morphometric {vessel diameter, vessel distribution, morphometry (shape), tortuosity, arteriole:venule (A:V) ratio, and hemosiderin deposits} and dynamic {vessel sludging/sludged flow, boxcar blood (trickled) flow and abnormal flow velocity} abnormalities. A severity index (SI) was computed to quantify the degree of vasculopathy for comparison between groups. The severity of vasculopathy differed significantly between the pediatric and adult patients (SI: 4.2 ± 1.8 vs 6.6 ± 2.4; p=0.028), indicative of a lesser degree of overall severity in the pediatric patients. Specific abnormalities that were less prominent in the pediatric patients included abnormal vessel morphometry and tortuosity. Sludged flow, abnormal vessel distribution, abnormal A:V ratio, and boxcar flow, appeared in high prevalence in both age groups. The results indicate that SCA microvascular abnormalities develop in childhood and the severity of vasculopathy likely progresses with age. Intervention and effective treatment/management modalities should target pediatric patients to ameliorate, slow down or prevent progressive microvascular deterioration. PMID:20872552

  14. 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 ...

  15. Auditory Thalamic Circuits and GABAA Receptor Function: Putative Mechanisms in Tinnitus Pathology

    PubMed Central

    Caspary, Donald M.; Llano, Daniel A

    2016-01-01

    Tinnitus is defined as a phantom sound (ringing in the ears), and can significantly reduce the quality of life for those who suffer its effects. Ten to fifteen percent of the general adult population report symptoms of tinnitus with 1-2% reporting that tinnitus negatively impacts their quality of life. Noise exposure is the most common cause of tinnitus and the military environment presents many challenging high-noise situations. Military noise levels can be so intense that standard hearing protection is not adequate. Recent studies suggest a role for inhibitory neurotransmitter dysfunction in response to noise-induced peripheral deafferentation as a key element in the pathology of tinnitus. The auditory thalamus, or medial geniculate body (MGB), is an obligate auditory brain center in a unique position to gate the percept of sound as it projects to auditory cortex and to limbic structures. Both areas are thought to be involved in those individuals most impacted by tinnitus. For MGB, opposing hypotheses have posited either a tinnitus-related pathologic decrease or pathologic increase in GABAergic inhibition. In sensory thalamus, GABA mediates fast synaptic inhibition via synaptic GABAA receptors (GABAARs) as well as a persistent tonic inhibition via high-affinity extrasynaptic GABAARs and slow synaptic inhibition via GABABRs. Down-regulation of inhibitory neurotransmission, related to partial peripheral deafferentation, is consistently presented as partially underpinning neuronal hyperactivity seen in animal models of tinnitus. This maladaptive plasticity/Gain Control Theory of tinnitus pathology (see Auerbach et al., 2014; Richardson et al., 2012) is characterized by reduced inhibition associated with increased spontaneous and abnormal neuronal activity, including bursting and increased synchrony throughout much of the central auditory pathway. A competing hypothesis suggests that maladaptive oscillations between the MGB and auditory cortex, thalamocortical

  16. Migration Pathways of Thalamic Neurons and Development of Thalamocortical Connections in Humans Revealed by Diffusion MR Tractography.

    PubMed

    Wilkinson, Molly; Kane, Tara; Wang, Rongpin; Takahashi, Emi

    2017-12-01

    The thalamus plays an important role in signal relays in the brain, with thalamocortical (TC) neuronal pathways linked to various sensory/cognitive functions. In this study, we aimed to see fetal and postnatal development of the thalamus including neuronal migration to the thalamus and the emergence/maturation of the TC pathways. Pathways from/to the thalami of human postmortem fetuses and in vivo subjects ranging from newborns to adults with no neurological histories were studied using high angular resolution diffusion MR imaging (HARDI) tractography. Pathways likely linked to neuronal migration from the ventricular zone and ganglionic eminence (GE) to the thalami were both successfully detected. Between the ventricular zone and thalami, more tractography pathways were found in anterior compared with posterior regions, which was well in agreement with postnatal observations that the anterior TC segment had more tract count and volume than the posterior segment. Three different pathways likely linked to neuronal migration from the GE to the thalami were detected. No hemispheric asymmetry of the TC pathways was quantitatively observed during development. These results suggest that HARDI tractography is useful to identify multiple differential neuronal migration pathways in human brains, and regional differences in brain development in fetal ages persisted in postnatal development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. 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 ...

  18. Characterization of thalamocortical association using amplitude and connectivity of fMRI in mild traumatic brain injury

    PubMed Central

    Zhou, Yongxia; Lui, Yvonne W; Zuo, Xi-Nian; Milham, Michael P.; Reaume, Joseph; Grossman, Robert I.; Ge, Yulin

    2013-01-01

    Purpose To examine thalamic and cortical injuries using fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity MRI (fcMRI) based on resting state (RS) and task-related fMRI in patients with mild traumatic brain injury (MTBI). Materials and Methods Twenty-seven patients and 27 age-matched controls were recruited. 3T fMRI at RS and finger tapping task were used to assess fALFF and fcMRI patterns. fALFF was computed with filtering (0.01-0.08Hz) and scaling after preprocessing. fcMRI was performed using a standard seed-based correlation method, and delayed fcMRI (coherence) in frequency domain were also performed between thalamus and cortex. Results In comparison with controls, MTBI patients exhibited significantly decreased fALFF in the thalamus (and frontal/temporal sub segments) and cortical frontal and temporal lobes; as well as decreased thalamo-thalamo and thalamo-frontal/thalamo-temporal fcMRI at rest based on RS-fMRI (corrected P<0.05). This thalamic and cortical disruption also existed at task-related condition in patients. Conclusion The decreased fALFF (i.e. lower neuronal activity) in the thalamus and its segments provides additional evidence of thalamic injury in patients with MTBI. Our findings of fALFF and fcMRI changes during motor task and resting state may offer insights into the underlying cause and primary location of disrupted thalamo-cortical networks after MTBI. PMID:24014176

  19. A corticothalamic switch: controlling the thalamus with dynamic synapses

    PubMed Central

    Crandall, Shane R.; Cruikshank, Scott J.; Connors, Barry W.

    2015-01-01

    SUMMARY Corticothalamic neurons provide massive input to the thalamus. This top-down projection may allow cortex to regulate sensory processing by modulating the excitability of thalamic cells. Layer 6 corticothalamic neurons monosynaptically excite thalamocortical cells, but also indirectly inhibit them by driving inhibitory cells of the thalamic reticular nucleus. Whether corticothalamic activity generally suppresses or excites the thalamus remains unclear. Here we show that the corticothalamic influence is dynamic, with the excitatory-inhibitory balance shifting in an activity-dependent fashion. During low-frequency activity corticothalamic effects are mainly suppressive, whereas higher frequency activity (even a short bout of gamma frequency oscillations) converts the corticothalamic influence to enhancement. The mechanism of this switching depends upon distinct forms of short-term synaptic plasticity across multiple corticothalamic circuit components. Our results reveal an activity-dependent mechanism by which corticothalamic neurons can bidirectionally switch the excitability and sensory throughput of the thalamus, possibly to meet changing behavioral demands. PMID:25913856

  20. Muscle abnormalities in osteogenesis imperfecta

    PubMed Central

    Veilleux, L-N.; Trejo, P.; Rauch, F.

    2017-01-01

    Osteogenesis imperfecta (OI) is mainly characterized by bone fragility but muscle abnormalities have been reported both in OI mouse models and in children with OI. Muscle mass is decreased in OI, even when short stature is taken into account. Dynamic muscle tests aiming at maximal eccentric force production reveal functional deficits that can not be explained by low muscle mass alone. However, it appears that diaphyseal bone mass is normally adapted to muscle force. At present the determinants of muscle mass and function in OI have not been clearly defined. Physiotherapy interventions and bisphosphonate treatment appear to have some effect on muscle function in OI. Interventions targeting muscle mass have shown encouraging results in OI animal models and are an interesting area for further research. PMID:28574406

  1. Improved segmentation of abnormal cervical nuclei using a graph-search based approach

    NASA Astrophysics Data System (ADS)

    Zhang, Ling; Liu, Shaoxiong; Wang, Tianfu; Chen, Siping; Sonka, Milan

    2015-03-01

    Reliable segmentation of abnormal nuclei in cervical cytology is of paramount importance in automation-assisted screening techniques. This paper presents a general method for improving the segmentation of abnormal nuclei using a graph-search based approach. More specifically, the proposed method focuses on the improvement of coarse (initial) segmentation. The improvement relies on a transform that maps round-like border in the Cartesian coordinate system into lines in the polar coordinate system. The costs consisting of nucleus-specific edge and region information are assigned to the nodes. The globally optimal path in the constructed graph is then identified by dynamic programming. We have tested the proposed method on abnormal nuclei from two cervical cell image datasets, Herlev and H and E stained liquid-based cytology (HELBC), and the comparative experiments with recent state-of-the-art approaches demonstrate the superior performance of the proposed method.

  2. 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

  3. Cerebellar ataxia: abnormal control of interaction torques across multiple joints.

    PubMed

    Bastian, A J; Martin, T A; Keating, J G; Thach, W T

    1996-07-01

    1. We studied seven subjects with cerebellar lesions and seven control subjects as they made reaching movements in the sagittal plane to a target directly in front of them. Reaches were made under three different conditions: 1) "slow-accurate," 2) "fast-accurate," and 3) "fast as possible." All subjects were videotaped moving in a sagittal plane with markers on the index finger, wrist, elbow, and shoulder. Marker positions were digitized and then used to calculate joint angles. For each of the shoulder, elbow and wrist joints, inverse dynamics equations based on a three-segment limb model were used to estimate the net torque (sum of components) and each of the component torques. The component torques consisted of the torque due to gravity, the dynamic interaction torques induced passively by the movement of the adjacent joint, and the torque produced by the muscles and passive tissue elements (sometimes called "residual" torque). 2. A kinematic analysis of the movement trajectory and the change in joint angles showed that the reaches of subjects with cerebellar lesions were abnormal compared with reaches of control subjects. In both the slow-accurate and fast-accurate conditions the cerebellar subjects made abnormally curved wrist paths; the curvature was greater in the slow-accurate condition. During the slow-accurate condition, cerebellar subjects showed target undershoot and tended to move one joint at a time (decomposition). During the fast-accurate reaches, the cerebellar subjects showed target overshoot. Additionally, in the fast-accurate condition, cerebellar subjects moved the joints at abnormal rates relative to one another, but the movements were less decomposed. Only three subjects were tested in the fast as possible condition; this condition was analyzed only to determine maximal reaching speeds of subjects with cerebellar lesions. Cerebellar subjects moved more slowly than controls in all three conditions. 3. A kinetic analysis of torques generated at

  4. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  5. Transition dynamics of generalized multiple epileptic seizures associated with thalamic reticular nucleus excitability: A computational study

    NASA Astrophysics Data System (ADS)

    Liu, Suyu; Wang, Qingyun

    2017-11-01

    Presently, we improve a computational framework of thalamocortical circuits related to the Taylor's model to investigate the relationship between thalamic reticular nucleus (RE) excitability and epilepsy. By using bifurcation analysis, we explore the RE's excitability dynamics mechanism in the processes of seizure generation, development and transition. Results show that the seizure-free state, absence seizures, clonic seizures and tonic seizures can be formed as the RE excitability is changed in this established model. Importantly, it is verified that physiological changing GABAA inhibition in RE can elicit absence seizures and clonic seizures and the pathological transitions between these two seizures. Furthermore, when the level of AMPA connection is decreased or increased, this proposed model embraces absence seizures and clonic seizures, and tonic seizures, respectively. Except that, bifurcation mechanisms of dynamical transition of different seizures are analyzed in detail. In addition, hybrid regulations of the reticular nucleus excitability for epileptic seizures are proven to be valid within the suitable levels of AMPA and GABAA connection. Hopefully, the obtained results could be helpful for effective control of epileptic activities with additional pharmacological interference.

  6. Monitoring abnormal bio-optical and physical properties in the Gulf of Mexico

    NASA Astrophysics Data System (ADS)

    Arnone, Robert; Jones, Brooke

    2017-05-01

    The dynamic bio-optical and physical ocean properties within the Gulf of Mexico (GoM) have been identified by the Ocean Weather Laboratory. Ocean properties from VIIRS satellite (Chlorophyll and Bio-Optics and SST) and ocean-circulation models (currents, SST and salinity) were used to identify regions of dynamic changing properties. The degree of environmental change is defined by the dynamic anomaly of bio-optical and physical environmental properties (DAP). A Mississippi River plume event (Aug 2015) that extended to Key West was used to demonstrate the anomaly products. Locations where normal and abnormal ocean properties occur determine ecological and physical hotspots in the GoM, which can be used for adaptive sampling of ocean processes. Methods are described to characterize the weekly abnormal environmental properties using differences with a previous baseline 8 week mean with a 2 week lag. The intensity of anomaly is quantified using levels of standard deviation of the baseline and can be used to recognize ocean events and provide decision support for adaptive sampling. The similarities of the locations of different environmental property anomalies suggest interaction between the bio-optical and physical properties. A coral bleaching event at the Flower Garden Banks Marine Protected Area is represented by the salinity anomaly. Results identify ocean regions for sampling to reduce data gaps and improve monitoring of bio-optical and physical properties.

  7. Retinal adaptation abnormalities in primary open-angle glaucoma.

    PubMed

    Dul, Mitchell; Ennis, Robert; Radner, Shira; Lee, Barry; Zaidi, Qasim

    2015-01-22

    Dynamic color and brightness adaptation are crucial for visual functioning. The effects of glaucoma on retinal ganglion cells (RGCs) could compromise these functions. We have previously used slow dynamic changes of light at moderate intensities to measure the speed and magnitude of subtractive adaptation in RGCs. We used the same procedure to test if RGC abnormalities cause slower and weaker adaptation for patients with glaucoma when compared to age-similar controls. We assessed adaptation deficits in specific classes of RGCs by testing along the three cardinal color axes that isolate konio, parvo, and magno RGCs. For one eye each of 10 primary open-angle glaucoma patients and their age-similar controls, we measured the speed and magnitude of adapting to 1/32 Hz color modulations along the three cardinal axes, at central fixation and 8° superior, inferior, nasal, and temporal to fixation. In all 15 comparisons (5 locations × 3 color axes), average adaptation was slower and weaker for glaucoma patients than for controls. Adaptation developed slower at central targets than at 8° eccentricities for controls, but not for patients. Adaptation speed and magnitude differed between affected and control eyes even at retinal locations showing no visual field loss with clinical perimetry. Neural adaptation is weaker in glaucoma patients for all three classes of RGCs. Since adaptation abnormalities are manifested even at retinal locations not exhibiting a visual field loss, this novel form of assessment may offer a functional insight into glaucoma and an early diagnosis tool. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  8. Retinal Adaptation Abnormalities in Primary Open-Angle Glaucoma

    PubMed Central

    Dul, Mitchell; Ennis, Robert; Radner, Shira; Lee, Barry; Zaidi, Qasim

    2015-01-01

    Purpose. Dynamic color and brightness adaptation are crucial for visual functioning. The effects of glaucoma on retinal ganglion cells (RGCs) could compromise these functions. We have previously used slow dynamic changes of light at moderate intensities to measure the speed and magnitude of subtractive adaptation in RGCs. We used the same procedure to test if RGC abnormalities cause slower and weaker adaptation for patients with glaucoma when compared to age-similar controls. We assessed adaptation deficits in specific classes of RGCs by testing along the three cardinal color axes that isolate konio, parvo, and magno RGCs. Methods. For one eye each of 10 primary open-angle glaucoma patients and their age-similar controls, we measured the speed and magnitude of adapting to 1/32 Hz color modulations along the three cardinal axes, at central fixation and 8° superior, inferior, nasal, and temporal to fixation. Results. In all 15 comparisons (5 locations × 3 color axes), average adaptation was slower and weaker for glaucoma patients than for controls. Adaptation developed slower at central targets than at 8° eccentricities for controls, but not for patients. Adaptation speed and magnitude differed between affected and control eyes even at retinal locations showing no visual field loss with clinical perimetry. Conclusions. Neural adaptation is weaker in glaucoma patients for all three classes of RGCs. Since adaptation abnormalities are manifested even at retinal locations not exhibiting a visual field loss, this novel form of assessment may offer a functional insight into glaucoma and an early diagnosis tool. PMID:25613950

  9. Synaptic changes in the thalamocortical system of cathepsin D-deficient mice: a model of human congenital neuronal ceroid-lipofuscinosis.

    PubMed

    Partanen, Sanna; Haapanen, Aleksi; Kielar, Catherine; Pontikis, Charles; Alexander, Noreen; Inkinen, Teija; Saftig, Paul; Gillingwater, Thomas H; Cooper, Jonathan D; Tyynelä, Jaana

    2008-01-01

    Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.

  10. Electrocardiographic abnormalities in opiate addicts.

    PubMed

    Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

    2008-12-01

    To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P < 0.05), and in patients with positive than negative urine findings for cannabis (68 versus 57%, P < 0.05). Patients with ST abnormalities were more often males than females (21 versus 11%, P < 0.05), had a history of seizures less often (16 versus 27%, P < 0.05), had positive than negative urine findings for cannabis more often (26 versus 15%, P < 0.01) and had negative than positive urine findings for methadone more often (21 versus 11%, P < 0.05). QTc prolongation was more frequent in patients with high dosages of maintenance drugs than in patients with medium or low dosages (27 versus 12 versus 10%, P < 0.05) and in patients whose urine findings were positive than negative for methadone (23 versus 11%, P < 0.001) as well as for benzodiazepines (17 versus 9%, P < 0.05). Limitations of the data are that in most cases other risk factors for the cardiac abnormalities were not known. ECG abnormalities are frequent in opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation

  11. Auditory thalamic circuits and GABAA receptor function: Putative mechanisms in tinnitus pathology.

    PubMed

    Caspary, Donald M; Llano, Daniel A

    2017-06-01

    , thalamocortical dysrhythmia, predict tinnitus pathology (De Ridder et al., 2015). These unusual oscillations/rhythms reflect net increased tonic inhibition in a subset of thalamocortical projection neurons resulting in abnormal bursting. Hyperpolarizing de-inactivation of T-type Ca2+ channels switches thalamocortical projection neurons into burst mode. Thalamocortical dysrhythmia originating in sensory thalamus has been postulated to underpin neuropathies including tinnitus and chronic pain. Here we review the relationship between noise-induced tinnitus and altered inhibition in the MGB. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Biochemical abnormalities in neonatal seizures.

    PubMed

    Sood, Arvind; Grover, Neelam; Sharma, Roshan

    2003-03-01

    The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

  13. Angelman syndrome: current understanding and research prospects.

    PubMed

    Dan, Bernard

    2009-11-01

    Angelman syndrome is a neurogenetic disorder characterized by developmental delay, severe intellectual disability, absent speech, exuberant behavior with happy demeanor, motor impairment, and epilepsy, due to deficient UBE3A gene expression that may be caused by various abnormalities of chromosome 15. Recent findings in animal models demonstrated altered dendritic spine formation as well as both synaptic [including gamma-aminobutyric acid (GABA)(A) and N-methyl-D-aspartate (NMDA) transmission] and nonsynaptic (including gap junction) influences in various brain regions, including hippocampus and cerebellar cortex. Reversal of selected abnormalities in rescue genetically engineered animal models is encouraging, although it should not be misinterpreted as promising "cure" for affected patients. Much research is still required to fully understand the functional links between lack of UBE3A expression and clinical manifestations of Angelman syndrome. Studies of regulation of UBE3A expression, including imprinting-related methylation, may point to possibilities of therapeutic upregulation. Understanding relevant roles of the gene product might lead to targeted intervention. Further documentation of brain network dynamics, with particular emphasis on hippocampus, thalamocortical, and cerebellar networks is needed, including in a developmental perspective. There is also a need for further clinical research for improving management of problems such as epilepsy, behavior, communication, learning, motor impairment, and sleep disturbances.

  14. Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes.

    PubMed

    Marshall, Nicole E; Fraley, Gwen; Feist, Cori; Burns, Michael J; Pereira, Leonardo

    2012-08-01

    To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity.

  15. Chromosomal abnormalities in human sperm

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

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhapsmore » reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.« less

  16. 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.

  17. Pyrosequencing reveals the microbial communities in the Red Sea sponge Carteriospongia foliascens and their impressive shifts in abnormal tissues.

    PubMed

    Gao, Zhao-Ming; Wang, Yong; Lee, On On; Tian, Ren-Mao; Wong, Yue Him; Bougouffa, Salim; Batang, Zenon; Al-Suwailem, Abdulaziz; Lafi, Feras F; Bajic, Vladimir B; Qian, Pei-Yuan

    2014-10-01

    Abnormality and disease in sponges have been widely reported, yet how sponge-associated microbes respond correspondingly remains inconclusive. Here, individuals of the sponge Carteriospongia foliascens under abnormal status were collected from the Rabigh Bay along the Red Sea coast. Microbial communities in both healthy and abnormal sponge tissues and adjacent seawater were compared to check the influences of these abnormalities on sponge-associated microbes. In healthy tissues, we revealed low microbial diversity with less than 100 operational taxonomic units (OTUs) per sample. Cyanobacteria, affiliated mainly with the sponge-specific species "Candidatus Synechococcus spongiarum," were the dominant bacteria, followed by Bacteroidetes and Proteobacteria. Intraspecies dynamics of microbial communities in healthy tissues were observed among sponge individuals, and potential anoxygenic phototrophic bacteria were found. In comparison with healthy tissues and the adjacent seawater, abnormal tissues showed dramatic increase in microbial diversity and decrease in the abundance of sponge-specific microbial clusters. The dominated cyanobacterial species Candidatus Synechococcus spongiarum decreased and shifted to unspecific cyanobacterial clades. OTUs that showed high similarity to sequences derived from diseased corals, such as Leptolyngbya sp., were found to be abundant in abnormal tissues. Heterotrophic Planctomycetes were also specifically enriched in abnormal tissues. Overall, we revealed the microbial communities of the cyanobacteria-rich sponge, C. foliascens, and their impressive shifts under abnormality.

  18. Inhibition of NMDARs in the Nucleus Reticularis of the Thalamus Produces Delta Frequency Bursting.

    PubMed

    Zhang, Yuchun; Llinas, Rodolfo R; Lisman, John E

    2009-01-01

    Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG oscillations in the thalamocortical system. It is surprising that an antagonist of an excitatory neurotransmitter should trigger such activity, and the mechanism is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic cells, thus producing disinhibition. To test this hypothesis, we investigated the effect of NMDAR antagonist (APV) on cells of the nucleus reticularis (nRT) in rat brain slices, a thalamic nucleus that can serve as a pacemaker for thalamocortical delta oscillations and that is composed entirely of GABAergic neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This occurs because these cells have an unusual form of NMDAR (probably NR2C) that contributes inward current at resting potential in response to ambient glutamate. The hyperpolarization produced by APV is sufficient to deinactivate T-type calcium channels, and these trigger rhythmic bursting at delta frequency. The APV-induced delta frequency bursting is abolished by dopamine D2 receptor antagonist, indicating that dopamine and NMDAR antagonist work synergistically to stimulate delta frequency bursting. Our results have significant implications concerning the electrophysiological basis of schizophrenia and bring together the NMDAR hypofunction, dopamine, and GABA theories of the disease. Our results suggest that NMDAR hypofunction and dopamine work synergistically on the GABAergic cells of the nRT to generate the delta frequency EEG oscillations, a thalamocortical dysrhythmia (TCD) in the awake state that is an established abnormality in schizophrenia.

  19. Inhibition of NMDARs in the Nucleus Reticularis of the Thalamus Produces Delta Frequency Bursting

    PubMed Central

    Zhang, Yuchun; Llinas, Rodolfo R.; Lisman, John E.

    2009-01-01

    Injection of NMDAR antagonist into the thalamus can produce delta frequency EEG oscillations in the thalamocortical system. It is surprising that an antagonist of an excitatory neurotransmitter should trigger such activity, and the mechanism is unknown. One hypothesis is that the antagonist blocks excitation of GABAergic cells, thus producing disinhibition. To test this hypothesis, we investigated the effect of NMDAR antagonist (APV) on cells of the nucleus reticularis (nRT) in rat brain slices, a thalamic nucleus that can serve as a pacemaker for thalamocortical delta oscillations and that is composed entirely of GABAergic neurons. We found, unexpectedly, that nRT cells are hyperpolarized by APV. This occurs because these cells have an unusual form of NMDAR (probably NR2C) that contributes inward current at resting potential in response to ambient glutamate. The hyperpolarization produced by APV is sufficient to deinactivate T-type calcium channels, and these trigger rhythmic bursting at delta frequency. The APV-induced delta frequency bursting is abolished by dopamine D2 receptor antagonist, indicating that dopamine and NMDAR antagonist work synergistically to stimulate delta frequency bursting. Our results have significant implications concerning the electrophysiological basis of schizophrenia and bring together the NMDAR hypofunction, dopamine, and GABA theories of the disease. Our results suggest that NMDAR hypofunction and dopamine work synergistically on the GABAergic cells of the nRT to generate the delta frequency EEG oscillations, a thalamocortical dysrhythmia (TCD) in the awake state that is an established abnormality in schizophrenia. PMID:20057928

  20. A combined static-dynamic single-dose imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT.

    PubMed

    Sciammarella, Maria; Shrestha, Uttam M; Seo, Youngho; Gullberg, Grant T; Botvinick, Elias H

    2017-08-03

    SPECT myocardial perfusion imaging (MPI) is a clinical mainstay that is typically performed with static imaging protocols and visually or semi-quantitatively assessed for perfusion defects based upon the relative intensity of myocardial regions. Dynamic cardiac SPECT presents a new imaging technique based on time-varying information of radiotracer distribution, which permits the evaluation of regional myocardial blood flow (MBF) and coronary flow reserve (CFR). In this work, a preliminary feasibility study was conducted in a small patient sample designed to implement a unique combined static-dynamic single-dose one-day visit imaging protocol to compare quantitative dynamic SPECT with static conventional SPECT for improving the diagnosis of coronary artery disease (CAD). Fifteen patients (11 males, four females, mean age 71 ± 9 years) were enrolled for a combined dynamic and static SPECT (Infinia Hawkeye 4, GE Healthcare) imaging protocol with a single dose of 99m Tc-tetrofosmin administered at rest and a single dose administered at stress in a one-day visit. Out of 15 patients, eleven had selective coronary angiography (SCA), 8 within 6 months and the rest within 24 months of SPECT imaging, without intervening symptoms or interventions. The extent and severity of perfusion defects in each myocardial region was graded visually. Dynamically acquired data were also used to estimate the MBF and CFR. Both visually graded images and estimated CFR were tested against SCA as a reference to evaluate the validity of the methods. Overall, conventional static SPECT was normal in ten patients and abnormal in five patients, dynamic SPECT was normal in 12 patients and abnormal in three patients, and CFR from dynamic SPECT was normal in nine patients and abnormal in six patients. Among those 11 patients with SCA, conventional SPECT was normal in 5, 3 with documented CAD on SCA with an overall accuracy of 64%, sensitivity of 40% and specificity of 83%. Dynamic SPECT image

  1. Studies of planning behavior of aircraft pilots in normal, abnormal, and emergency situations

    NASA Technical Reports Server (NTRS)

    Johannsen, G.; Rouse, W. B.; Hillmann, K.

    1981-01-01

    A methodology for the study of human planning behavior in complex dynamic systems is presented and applied to the study of aircraft pilot behavior in normal, abnormal and emergency situations. The method measures the depth of planning, that is the level of detail employed with respect to a specific task, according to responses to a verbal questionnaire, and compares planning depth with variables relating to time, task criticality and the probability of increased task difficulty. In two series of experiments, depth of planning was measured on a five- or ten-point scale during various phases of flight in a HFB-320 simulator under normal flight conditions, abnormal scenarios involving temporary runway closure due to snow removal or temporary CAT-III conditions due to a dense fog, and emergency scenarios involving engine shut-down or hydraulic pressure loss. Results reveal a dichotomy between event-driven and time-driven planning, different effects of automation in abnormal and emergency scenarios and a low correlation between depth of planning and workload or flight performance.

  2. Anatomy of the auditory thalamocortical system in the Mongolian gerbil: nuclear origins and cortical field-, layer-, and frequency-specificities.

    PubMed

    Saldeitis, Katja; Happel, Max F K; Ohl, Frank W; Scheich, Henning; Budinger, Eike

    2014-07-01

    Knowledge of the anatomical organization of the auditory thalamocortical (TC) system is fundamental for the understanding of auditory information processing in the brain. In the Mongolian gerbil (Meriones unguiculatus), a valuable model species in auditory research, the detailed anatomy of this system has not yet been worked out in detail. Here, we investigated the projections from the three subnuclei of the medial geniculate body (MGB), namely, its ventral (MGv), dorsal (MGd), and medial (MGm) divisions, as well as from several of their subdivisions (MGv: pars lateralis [LV], pars ovoidea [OV], rostral pole [RP]; MGd: deep dorsal nucleus [DD]), to the auditory cortex (AC) by stereotaxic pressure injections and electrophysiologically guided iontophoretic injections of the anterograde tract tracer biocytin. Our data reveal highly specific features of the TC connections regarding their nuclear origin in the subdivisions of the MGB and their termination patterns in the auditory cortical fields and layers. In addition to tonotopically organized projections, primarily of the LV, OV, and DD to the AC, a large number of axons diverge across the tonotopic gradient. These originate mainly from the RP, MGd (proper), and MGm. In particular, neurons of the MGm project in a columnar fashion to several auditory fields, forming small- and medium-sized boutons, and also hitherto unknown giant terminals. The distinctive layer-specific distribution of axonal endings within the AC indicates that each of the TC connectivity systems has a specific function in auditory cortical processing. Copyright © 2014 Wiley Periodicals, Inc.

  3. In vivo wide-field calcium imaging of mouse thalamocortical synapses with an 8 K ultra-high-definition camera.

    PubMed

    Yoshida, Eriko; Terada, Shin-Ichiro; Tanaka, Yasuyo H; Kobayashi, Kenta; Ohkura, Masamichi; Nakai, Junichi; Matsuzaki, Masanori

    2018-05-29

    In vivo wide-field imaging of neural activity with a high spatio-temporal resolution is a challenge in modern neuroscience. Although two-photon imaging is very powerful, high-speed imaging of the activity of individual synapses is mostly limited to a field of approximately 200 µm on a side. Wide-field one-photon epifluorescence imaging can reveal neuronal activity over a field of ≥1 mm 2 at a high speed, but is not able to resolve a single synapse. Here, to achieve a high spatio-temporal resolution, we combine an 8 K ultra-high-definition camera with spinning-disk one-photon confocal microscopy. This combination allowed us to image a 1 mm 2 field with a pixel resolution of 0.21 µm at 60 fps. When we imaged motor cortical layer 1 in a behaving head-restrained mouse, calcium transients were detected in presynaptic boutons of thalamocortical axons sparsely labeled with GCaMP6s, although their density was lower than when two-photon imaging was used. The effects of out-of-focus fluorescence changes on calcium transients in individual boutons appeared minimal. Axonal boutons with highly correlated activity were detected over the 1 mm 2 field, and were probably distributed on multiple axonal arbors originating from the same thalamic neuron. This new microscopy with an 8 K ultra-high-definition camera should serve to clarify the activity and plasticity of widely distributed cortical synapses.

  4. The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

    PubMed Central

    Zagha, Edward; Mato, German; Rudy, Bernardo; Nadal, Marcela S.

    2014-01-01

    The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing Ih (hyperpolarization-activated cationic current), IT (low-threshold calcium current), and INaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of IA (fast transient A-type potassium current) and IKir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between three amplifying variables (activation of IT, activation of INaP, and activation of IKir) and three recovering variables (inactivation of IT, activation of IA, and activation of Ih) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation. PMID:24760784

  5. Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability.

    PubMed

    Umile, Eric M; Sandel, M Elizabeth; Alavi, Abass; Terry, Charles M; Plotkin, Rosette C

    2002-11-01

    To determine whether patients with mild traumatic brain injury (TBI) and persistent postconcussive symptoms have evidence of temporal lobe injury on dynamic imaging. Case series. An academic medical center. Twenty patients with a clinical diagnosis of mild TBI and persistent postconcussive symptoms were referred for neuropsychologic evaluation and dynamic imaging. Fifteen (75%) had normal magnetic resonance imaging (MRI) and/or computed tomography (CT) scans at the time of injury. Neuropsychologic testing, positron-emission tomography (PET), and single-photon emission-computed tomography (SPECT). Temporal lobe findings on static imaging (MRI, CT) and dynamic imaging (PET, SPECT); neuropsychologic test findings on measures of verbal and visual memory. Testing documented neurobehavioral deficits in 19 patients (95%). Dynamic imaging documented abnormal findings in 18 patients (90%). Fifteen patients (75%) had temporal lobe abnormalities on PET and SPECT (primarily in medial temporal regions); abnormal findings were bilateral in 10 patients (50%) and unilateral in 5 (25%). Six patients (30%) had frontal abnormalities, and 8 (40%) had nonfrontotemporal abnormalities. Correlations between neuropsychologic testing and dynamic imaging could be established but not consistently across the whole group. Patients with mild TBI and persistent postconcussive symptoms have a high incidence of temporal lobe injury (presumably involving the hippocampus and related structures), which may explain the frequent finding of memory disorders in this population. The abnormal temporal lobe findings on PET and SPECT in humans may be analogous to the neuropathologic evidence of medial temporal injury provided by animal studies after mild TBI. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  6. Cortical and thalamic contributions to response dynamics across layers of the primary somatosensory cortex during tactile discrimination

    PubMed Central

    Pais-Vieira, Miguel; Kunicki, Carolina; Tseng, Po-He; Martin, Joel; Lebedev, Mikhail

    2015-01-01

    Tactile information processing in the rodent primary somatosensory cortex (S1) is layer specific and involves modulations from both thalamocortical and cortico-cortical loops. However, the extent to which these loops influence the dynamics of the primary somatosensory cortex while animals execute tactile discrimination remains largely unknown. Here, we describe neural dynamics of S1 layers across the multiple epochs defining a tactile discrimination task. We observed that neuronal ensembles within different layers of the S1 cortex exhibited significantly distinct neurophysiological properties, which constantly changed across the behavioral states that defined a tactile discrimination. Neural dynamics present in supragranular and granular layers generally matched the patterns observed in the ventral posterior medial nucleus of the thalamus (VPM), whereas the neural dynamics recorded from infragranular layers generally matched the patterns from the posterior nucleus of the thalamus (POM). Selective inactivation of contralateral S1 specifically switched infragranular neural dynamics from POM-like to those resembling VPM neurons. Meanwhile, ipsilateral M1 inactivation profoundly modulated the firing suppression observed in infragranular layers. This latter effect was counterbalanced by contralateral S1 block. Tactile stimulus encoding was layer specific and selectively affected by M1 or contralateral S1 inactivation. Lastly, causal information transfer occurred between all neurons in all S1 layers but was maximal from infragranular to the granular layer. These results suggest that tactile information processing in the S1 of awake behaving rodents is layer specific and state dependent and that its dynamics depend on the asynchronous convergence of modulations originating from ipsilateral M1 and contralateral S1. PMID:26180115

  7. The SEEKING mind: primal neuro-affective substrates for appetitive incentive states and their pathological dynamics in addictions and depression.

    PubMed

    Alcaro, Antonio; Panksepp, Jaak

    2011-10-01

    Appetitive motivation and incentive states are essential functions sustained by a common emotional brain process, the SEEKING disposition, which drives explorative and approach behaviors, sustains goal-directed activity, promotes anticipatory cognitions, and evokes feelings of positive excitement which control reward-learning. All such functions are orchestrated by the same "archetypical" neural processes, activated in ancient subcortical areas and transported to the forebrain by the mesolimbic dopamine (ML-DA) system. In mammals, the neurophysiology of the SEEKING urge is expressed by DA-promoted high-frequency oscillations, in the form of transient and synchronized gamma waves (>30Hz) emerging in limbic forebrain and diffusing throughout basal ganglia-thalamocortical (BG-T-C) circuits. These patterns may be considered basic "SEEKING neurodynamic impulses" which represent the primary-process exploratory disposition getting integrated with information relative to the external and the internal environment. Abnormal manifestation of SEEKING and its neural substrates are evident in clinical depression and addiction. Specifically, depression is characterized by reduced recruitment of SEEKING, while addictions reflect re-organizations of the SEEKING disposition around ultra-specific appetitive memories and compulsive activities. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Effect of Developmental Binocular Vision Abnormalities on Visual Vertigo Symptoms and Treatment Outcome.

    PubMed

    Pavlou, Marousa; Acheson, James; Nicolaou, Despina; Fraser, Clare L; Bronstein, Adolfo M; Davies, Rosalyn A

    2015-10-01

    Customized vestibular rehabilitation incorporating optokinetic (OK) stimulation improves visual vertigo (VV) symptoms; however, the degree of improvement varies among individuals. Binocular vision abnormalities (misalignment of ocular axis, ie, strabismus) may be a potential risk factor. This study aimed to investigate the influence of binocular vision abnormalities on VV symptoms and treatment outcome. Sixty subjects with refractory peripheral vestibular symptoms underwent an orthoptic assessment after being recruited for participation in an 8-week customized program incorporating OK training via a full-field visual environment rotator or video display, supervised or unsupervised. Treatment response was assessed at baseline and at 8 weeks with dynamic posturography, Functional Gait Assessment (FGA), and questionnaires for symptoms, symptom triggers, and psychological state. As no significant effect of OK training type was noted for any variables, data were combined and new groups identified on the basis of the absence or presence of a binocular vision abnormality. A total of 34 among 60 subjects consented to the orthoptic assessment, of whom 8 of the 34 had binocular vision abnormalities and 30 of the 34 subjects completed both the binocular function assessment and vestibular rehabilitation program. No significant between-group differences were noted at baseline. The only significant between-group difference was observed for pre-/post-VV symptom change (P = 0.01), with significant improvements noted only for the group without binocular vision abnormalities (P < 0.0005). Common vestibular symptoms, posturography, and the FGA improved significantly for both groups (P < 0.05). Binocular vision abnormalities may affect VV symptom improvement. These findings may have important implications for the management of subjects with refractory vestibular symptoms.Video Abstract available for insights from the authors regarding clinical implication of the study findings (see

  9. Lack of tryptophan hydroxylase-1 in mice results in gait abnormalities.

    PubMed

    Suidan, Georgette L; Duerschmied, Daniel; Dillon, Gregory M; Vanderhorst, Veronique; Hampton, Thomas G; Wong, Siu Ling; Voorhees, Jaymie R; Wagner, Denisa D

    2013-01-01

    The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (-/-) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system.

  10. Neurologic abnormalities in murderers.

    PubMed

    Blake, P Y; Pincus, J H; Buckner, C

    1995-09-01

    Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

  11. Aircraft Abnormal Conditions Detection, Identification, and Evaluation Using Innate and Adaptive Immune Systems Interaction

    NASA Astrophysics Data System (ADS)

    Al Azzawi, Dia

    Abnormal flight conditions play a major role in aircraft accidents frequently causing loss of control. To ensure aircraft operation safety in all situations, intelligent system monitoring and adaptation must rely on accurately detecting the presence of abnormal conditions as soon as they take place, identifying their root cause(s), estimating their nature and severity, and predicting their impact on the flight envelope. Due to the complexity and multidimensionality of the aircraft system under abnormal conditions, these requirements are extremely difficult to satisfy using existing analytical and/or statistical approaches. Moreover, current methodologies have addressed only isolated classes of abnormal conditions and a reduced number of aircraft dynamic parameters within a limited region of the flight envelope. This research effort aims at developing an integrated and comprehensive framework for the aircraft abnormal conditions detection, identification, and evaluation based on the artificial immune systems paradigm, which has the capability to address the complexity and multidimensionality issues related to aircraft systems. Within the proposed framework, a novel algorithm was developed for the abnormal conditions detection problem and extended to the abnormal conditions identification and evaluation. The algorithm and its extensions were inspired from the functionality of the biological dendritic cells (an important part of the innate immune system) and their interaction with the different components of the adaptive immune system. Immunity-based methodologies for re-assessing the flight envelope at post-failure and predicting the impact of the abnormal conditions on the performance and handling qualities are also proposed and investigated in this study. The generality of the approach makes it applicable to any system. Data for artificial immune system development were collected from flight tests of a supersonic research aircraft within a motion-based flight

  12. Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

    PubMed

    Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

    2017-04-01

    The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks

  13. Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing

    PubMed Central

    Sankarasubramanian, Vishwanath; Cunningham, David A.; Potter-Baker, Kelsey A.; Beall, Erik B.; Roelle, Sarah M.; Varnerin, Nicole M.; Machado, Andre G.; Jones, Stephen E.; Lowe, Mark J.

    2017-01-01

    Abstract The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory

  14. Dandy-Walker syndrome and chromosomal abnormalities.

    PubMed

    Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

    2007-12-01

    Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

  15. Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation

    PubMed Central

    Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H.

    2013-01-01

    A typical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). “Neurally impaired” versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands, and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable’s motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

  16. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

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

    Grossman, S.A.; Trump, D.L.; Chen, D.C.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizingmore » these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.« less

  17. Genetic Evidence for a Role for Protein Kinase A in the Maintenance of Sleep and Thalamocortical Oscillations

    PubMed Central

    Hellman, Kevin; Hernandez, Pepe; Park, Alice; Abel, Ted

    2010-01-01

    Study Objectives: Genetic manipulation of cAMP-dependent protein kinase A (PKA) in Drosophila has implicated an important role for PKA in sleep/wake state regulation. Here, we characterize the role of this signaling pathway in the regulation of sleep using electroencephalographic (EEG) and electromyographic (EMG) recordings in R(AB) transgenic mice that express a dominant negative form of the regulatory subunit of PKA in neurons within cortex and hippocampus. Previous studies have revealed that these mutant mice have reduced PKA activity that results in the impairment of hippocampus-dependent long-term memory and long-lasting forms of hippocampal synaptic plasticity. Design: PKA assays, in situ hybridization, immunoblots, and sleep studies were performed in R(AB) transgenic mice and wild-type control mice. Measurements and Results: We have found that R(AB) transgenic mice have reduced PKA activity within cortex and reduced Ser845 phosphorylation of the glutamate receptor subunit GluR1. R(AB) transgenic mice exhibit non-rapid eye movement (NREM) sleep fragmentation and increased amounts of rapid eye movement (REM) sleep relative to wild-type mice. Further, R(AB) transgenic mice have more delta power but less sigma power during NREM sleep relative to wild-type mice. After sleep deprivation, the amounts of NREM and REM sleep were comparable between wild-type and R(AB) transgenic mice. However, the homeostatic rebound of sigma power in R(AB) transgenic mice was reduced. Conclusions: Alterations in cortical synaptic receptors, impairments in sleep continuity, and alterations in sleep oscillations in R(AB) mice imply that PKA is involved not only in synaptic plasticity and memory storage but also in the regulation of sleep/wake states. Citation: Hellman K; Hernandez P; Park A; Abel T. Genetic evidence for a role for protein kinase a in the maintenance of sleep and thalamocortical oscillations. SLEEP 2010;33(1):19-28. PMID:20120617

  18. Neural responses of rat cortical layers due to infrared neural modulation and photoablation of thalamocortical brain slices

    NASA Astrophysics Data System (ADS)

    Jenkins, J. Logan; Kao, Chris C.; Cayce, Jonathan M.; Mahadevan-Jansen, Anita; Jansen, E. Duco

    2017-02-01

    Infrared neural modulation (INM) is a label-free method for eliciting neural activity with high spatial selectivity in mammalian models. While there has been an emphasis on INM research towards applications in the peripheral nervous system and the central nervous system (CNS), the biophysical mechanisms by which INM occurs remains largely unresolved. In the rat CNS, INM has been shown to elicit and inhibit neural activity, evoke calcium signals that are dependent on glutamate transients and astrocytes, and modulate inhibitory GABA currents. So far, in vivo experiments have been restricted to layers I and II of the rat cortex which consists mainly of astrocytes, inhibitory neurons, and dendrites from deeper excitatory neurons owing to strong absorption of light in these layers. Deeper cortical layers (III-VI) have vastly different cell type composition, consisting predominantly of excitatory neurons which can be targeted for therapies such as deep brain stimulation. The neural responses to infrared light of deeper cortical cells have not been well defined. Acute thalamocortical brain slices will allow us to analyze the effects of INS on various components of the cortex, including different cortical layers and cell populations. In this study, we present the use of photoablation with an erbium:YAG laser to reduce the thickness of the dead cell zone near the cutting surface of brain slices. This technique will allow for more optical energy to reach living cells, which should contribute the successful transduction of pulsed infrared light to neural activity. In the future, INM-induced neural responses will lead to a finer characterization of the parameter space for the neuromodulation of different cortical cell types and may contribute to understanding the cell populations that are important for allowing optical stimulation of neurons in the CNS.

  19. Detecting Abnormal Vehicular Dynamics at Intersections Based on an Unsupervised Learning Approach and a Stochastic Model

    PubMed Central

    Jiménez-Hernández, Hugo; González-Barbosa, Jose-Joel; Garcia-Ramírez, Teresa

    2010-01-01

    This investigation demonstrates an unsupervised approach for modeling traffic flow and detecting abnormal vehicle behaviors at intersections. In the first stage, the approach reveals and records the different states of the system. These states are the result of coding and grouping the historical motion of vehicles as long binary strings. In the second stage, using sequences of the recorded states, a stochastic graph model based on a Markovian approach is built. A behavior is labeled abnormal when current motion pattern cannot be recognized as any state of the system or a particular sequence of states cannot be parsed with the stochastic model. The approach is tested with several sequences of images acquired from a vehicular intersection where the traffic flow and duration used in connection with the traffic lights are continuously changed throughout the day. Finally, the low complexity and the flexibility of the approach make it reliable for use in real time systems. PMID:22163616

  20. Detecting abnormal vehicular dynamics at intersections based on an unsupervised learning approach and a stochastic model.

    PubMed

    Jiménez-Hernández, Hugo; González-Barbosa, Jose-Joel; Garcia-Ramírez, Teresa

    2010-01-01

    This investigation demonstrates an unsupervised approach for modeling traffic flow and detecting abnormal vehicle behaviors at intersections. In the first stage, the approach reveals and records the different states of the system. These states are the result of coding and grouping the historical motion of vehicles as long binary strings. In the second stage, using sequences of the recorded states, a stochastic graph model based on a Markovian approach is built. A behavior is labeled abnormal when current motion pattern cannot be recognized as any state of the system or a particular sequence of states cannot be parsed with the stochastic model. The approach is tested with several sequences of images acquired from a vehicular intersection where the traffic flow and duration used in connection with the traffic lights are continuously changed throughout the day. Finally, the low complexity and the flexibility of the approach make it reliable for use in real time systems.

  1. Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors.

    PubMed

    Dimopoulou, Ioanna; Tsagarakis, Stylianos; Theodorakopoulou, Maria; Douka, Evangelia; Zervou, Maria; Kouyialis, Andreas T; Thalassinos, Nikolaos; Roussos, Charis

    2004-06-01

    To investigate the incidence and type of endocrine abnormalities in critical care patients with traumatic brain injury (TBI) and to examine their relationships to possible predisposing factors. Prospective study. General intensive care unit in a university hospital. Thirty-four TBI patients (27 men, 7 women), having a mean age of 37+/-16 years, were studied after weaning from mechanical ventilation. Baseline endocrine assessment was carried out by measuring cortisol, corticotropin, dehydroepiandrosterone sulfate, free thyroxine, thyrotropin (TSH), testosterone, oestradiol, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, growth hormone and insulin-like growth factor I. Dynamic evaluation was performed by human corticotropin releasing hormone and growth hormone releasing hormone in all patients. Male patients underwent additional investigation with gonadotropin-releasing hormone. Severity of neurological derangement was graded according to Glasgow Coma Scale (GCS), Marshall Computerized Tomographic Classification and intracranial pressure (ICP) levels. Eighteen of the 34 patients (53%) had an abnormal result in at least one hormonal axis tested, with cortisol hyporesponsiveness and gonadal dysfunction being equally common, affecting 24% of patients. Endocrine abnormalities were associated with a higher brain CT-scan classification score ( p=0.02). The GCS on admission correlated positively with baseline FSH (r=0.37, p=0.03), peak FSH (r=0.41, p=0.03), testosterone (r=0.44, p=0.02) and TSH (r=0.39, p=0.03). There were no relations between ICP(max) and any baseline or dynamic hormone measurements. Patients with TBI receiving critical care show changes in their neuroendocrine responses, which depend upon clinical and radiological measures of head injury severity. Most common abnormalities include cortisol hyporesponsiveness and hypogonadism.

  2. Pinna abnormalities and low-set ears

    MedlinePlus

    ... Pinna abnormalities; Genetic defect - pinna; Congenital defect - pinna Images Ear abnormalities Pinna of the newborn ear References Haddad J, Keesecker S. Congenital malformations. In: Kliegman RM, Stanton BF, ...

  3. Dysmorphometrics: the modelling of morphological abnormalities.

    PubMed

    Claes, Peter; Daniels, Katleen; Walters, Mark; Clement, John; Vandermeulen, Dirk; Suetens, Paul

    2012-02-06

    The study of typical morphological variations using quantitative, morphometric descriptors has always interested biologists in general. However, unusual examples of form, such as abnormalities are often encountered in biomedical sciences. Despite the long history of morphometrics, the means to identify and quantify such unusual form differences remains limited. A theoretical concept, called dysmorphometrics, is introduced augmenting current geometric morphometrics with a focus on identifying and modelling form abnormalities. Dysmorphometrics applies the paradigm of detecting form differences as outliers compared to an appropriate norm. To achieve this, the likelihood formulation of landmark superimpositions is extended with outlier processes explicitly introducing a latent variable coding for abnormalities. A tractable solution to this augmented superimposition problem is obtained using Expectation-Maximization. The topography of detected abnormalities is encoded in a dysmorphogram. We demonstrate the use of dysmorphometrics to measure abrupt changes in time, asymmetry and discordancy in a set of human faces presenting with facial abnormalities. The results clearly illustrate the unique power to reveal unusual form differences given only normative data with clear applications in both biomedical practice & research.

  4. Congenital Abnormalities

    MedlinePlus

    ... tube defects. However, there is also a genetic influence to this type of congenital anomaly. Unknown Causes The vast majority of congenital abnormalities have no known cause. This is particularly troubling for parents who plan to have more children, because there is no way to predict if ...

  5. Frequency of metabolic abnormalities in urinary stones patients.

    PubMed

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-11-01

    To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients.

  6. Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

    PubMed Central

    Suidan, Georgette L.; Vanderhorst, Veronique; Hampton, Thomas G.; Wong, Siu Ling; Voorhees, Jaymie R.; Wagner, Denisa D.

    2013-01-01

    The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (−/−) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system. PMID:23516593

  7. Abnormal Cervical Cancer Screening Test Results

    MedlinePlus

    ... FAQ187 GYNECOLOGIC PROBLEMS Abnormal Cervical Cancer Screening Test Results • What is cervical cancer screening? • What causes abnormal cervical cancer screening test results? • What is the difference between the terms cervical ...

  8. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  9. What proportion of congenital abnormalities can be prevented?

    PubMed Central

    Czeizel, A E; Intôdy, Z; Modell, B

    1993-01-01

    OBJECTIVE--To estimate the proportion of preventable congenital abnormalities in Hungary. DESIGN--Analysis of available Hungarian data-bases and of the effectiveness of primary, secondary, and tertiary preventive methods. SETTING--Databases of ad hoc epidemiological studies and of the Hungarian congenital abnormality registry. MAIN OUTCOME MEASURES--Prevalence at birth and prevalence after prevention in 73 congenital abnormality types or groups. RESULTS--Preventive methods are available for 51 (70%) of the 73 congenital abnormality types or groups evaluated. The birth prevalence of all congenital abnormalities could be reduced from 65 to 26 per 1000; thus 39 per 1000 (60%) are preventable. Without congenital dislocation of the hip, which is unusually common in Hungary, the preventable proportion of congenital abnormalities is 52%. CONCLUSION--Many congenital abnormalities can be prevented, but as they do not represent a single pathological category there is no single strategy for their prevention. Images p502-a p503-a PMID:8448464

  10. The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles.

    PubMed

    Fan, Denggui; Liao, Fucheng; Wang, Qingyun

    2017-07-01

    Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE→TC→Cortex. Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 →TC 1 →Cortex 1 and Cortex 1 →Cortex 2 →Cortex 3

  11. The pacemaker role of thalamic reticular nucleus in controlling spike-wave discharges and spindles

    NASA Astrophysics Data System (ADS)

    Fan, Denggui; Liao, Fucheng; Wang, Qingyun

    2017-07-01

    Absence epilepsy, characterized by 2-4 Hz spike-wave discharges (SWDs), can be caused by pathological interactions within the thalamocortical system. Cortical spindling oscillations are also demonstrated to involve the oscillatory thalamocortical rhythms generated by the synaptic circuitry of the thalamus and cortex. This implies that SWDs and spindling oscillations can share the common thalamocortical mechanism. Additionally, the thalamic reticular nucleus (RE) is hypothesized to regulate the onsets and propagations of both the epileptic SWDs and sleep spindles. Based on the proposed single-compartment thalamocortical neural field model, we firstly investigate the stimulation effect of RE on the initiations, terminations, and transitions of SWDs. It is shown that the activations and deactivations of RE triggered by single-pulse stimuli can drive the cortical subsystem to behave as the experimentally observed onsets and self-abatements of SWDs, as well as the transitions from 2-spike and wave discharges (2-SWDs) to SWDs. In particular, with increasing inhibition from RE to the specific relay nucleus (TC), rich transition behaviors in cortex can be obtained through the upstream projection path, RE → TC → Cortex . Although some of the complex dynamical patterns can be expected from the earlier single compartment thalamocortical model, the effect of brain network topology on the emergence of SWDs and spindles, as well as the transitions between them, has not been fully investigated. We thereby develop a spatially extended 3-compartment coupled network model with open-/closed-end connective configurations, to investigate the spatiotemporal effect of RE on the SWDs and spindles. Results show that the degrees of activations of RE 1 can induce the rich spatiotemporal evolution properties including the propagations from SWDs to spindles within different compartments and the transitions between them, through the RE 1 → TC 1 → Cortex 1 and Cortex 1 → Cortex 2

  12. Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

    PubMed

    Jiang, Ze Dong

    2013-08-01

    Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

  13. Frequency of metabolic abnormalities in urinary stones patients

    PubMed Central

    Ahmad, Iftikhar; Pansota, Mudassar Saeed; Tariq, Muhammad; Tabassum, Shafqat Ali

    2013-01-01

    Objective: To determine the frequency of metabolic abnormalities in the serum and urine of patients with urinary stones disease. Methods: Two hundred patients with either multiple or recurrent urolithiasis diagnosed on ultrasonography and intravenous urography were included in this study. 24 hour urine sample were collected from each patient and sent for PH, specific gravity, Creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. In addition, blood sample of each patient was also sent for serum levels of urea, creatinine, uric acid, phosphate and calcium. Results: Mean age of patients was 38 ± 7.75 years with male to female ratio of 2:1. The main presenting complaint was lumber pain and 82.5% patients were found to have calcium oxalate stones on chemical analysis. Metabolic abnormalities were found in 90.5% patients, whereas there were no metabolic abnormalities in 19 (9.5%) patients. Forty patients (21.5%) only had one metabolic abnormality and 157 (78.5%) patients had multiple metabolic abnormalities. Hyperoxaluria was the most commonly observed metabolic abnormality and was found in 64.5% patients. Other significant metabolic abnormalities were hypercalciuria, Hypercalcemia, hypocitraturia and hyperuricemia. Conclusion: This study concludes that frequency of metabolic abnormalities is very high in patients with urolithiasis and hyperoxaluria, hypercalciuria and hypocitraturia are the most important metabolic abnormalities observed in these patients. PMID:24550954

  14. Abnormal UP/DOWN Membrane Potential Dynamics Coupled with the Neocortical Slow Oscillation in Dentate Granule Cells during the Latent Phase of Temporal Lobe Epilepsy.

    PubMed

    Ouedraogo, David W; Lenck-Santini, Pierre-Pascal; Marti, Geoffrey; Robbe, David; Crépel, Valérie; Epsztein, Jérôme

    2016-01-01

    The dentate gyrus, a major entry point to the hippocampus, gates (or filters) incoming information from the cortex. During sleep or anesthesia, the slow-wave oscillation (SWO) orchestrates hippocampus-neocortex communication, which is important for memory formation. The dentate gate is altered in temporal lobe epilepsy (TLE) early during epileptogenesis, which favors the propagation of pathological activities. Yet, whether the gating of physiological SWO by dentate granule cells (DGCs) is altered in TLE has remained unexplored. We combined intracellular recordings of membrane potential (V m) of DGCs and local field potential recordings of the SWO in parietal cortex in anesthetized rats early during epileptogenesis [post-status epilepticus (SE) rats]. As expected, in control rats, the V m of DGCs weakly and rarely oscillated in the SWO frequency range. In contrast, in post-SE rats, the V m of DGCs displayed strong and long-lasting SWO. In these cells, clear UP and DOWN states, in phase with the neocortical SWO, led to a bimodal V m distribution. In post-SE rats, the firing of DGCs was increased and more temporally modulated by the neocortical SWO. We conclude that UP/DOWN state dynamics dominate the V m of DGCs and firing early during epileptogenesis. This abnormally strong neocortical influence on the dynamics of DGCs may profoundly modify the hippocampus-neocortex dialogue during sleep and associated cognitive functions.

  15. Natural history of echocardiographic abnormalities in mucopolysaccharidosis III.

    PubMed

    Wilhelm, Carolyn M; Truxal, Kristen V; McBride, Kim L; Kovalchin, John P; Flanigan, Kevin M

    2018-06-01

    Mucopolysaccharidosis (MPS) type III, Sanfilippo Syndrome, is an autosomal recessive lysosomal storage disorder. MPS I and II patients often develop cardiac involvement leading to early mortality, however there are limited data in MPS III. The objective of this study is to describe cardiac abnormalities in a large group of MPS III patients followed in a longitudinal natural history study designed to determine outcome measures for gene transfer trials. A single center study of MPS III patients who were enrolled in the Nationwide Children's Hospital natural history study in 2014. Two cardiologists reviewed all patient echocardiograms for anatomic, valvular, and functional abnormalities. Valve abnormalities were defined as abnormal morphology, trivial mitral regurgitation (MR) with abnormal morphology or at least mild MR, and any aortic regurgitation (AR). Abnormal left ventricular (LV) function was defined as ejection fraction < 50%. Group comparisons were assessed using two-sample t-tests or Wilcoxon rank sum tests for continuous variables and chi-square or Fisher's exact tests for categorical variables. Twenty-five patients, 15 Type A and 10 Type B MPS III, underwent 45 echocardiograms. Fifteen patients (60%) demonstrated an abnormal echocardiographic finding with age at first abnormal echocardiogram within the study being 6.8 ± 2.8 years. Left-sided valve abnormalities were common over time: 7 mitral valve thickening, 2 mitral valve prolapse, 16 MR (8 mild, 8 trivial), 3 aortic valve thickening, and 9 AR (7 mild, 2 trivial). Two patients had asymmetric LV septal hypertrophy. No valvular stenosis or ventricular function abnormalities were noted. Incidental findings included: mild aortic root dilation (2), bicommissural aortic valve (1), and mild tricuspid regurgitation (3). Individuals with Sanfilippo A and B demonstrate a natural history of cardiac involvement with valvular abnormalities most common. In short-term follow up, patients demonstrated only

  16. Ergonomics for enhancing detection of machine abnormalities.

    PubMed

    Illankoon, Prasanna; Abeysekera, John; Singh, Sarbjeet

    2016-10-17

    Detecting abnormal machine conditions is of great importance in an autonomous maintenance environment. Ergonomic aspects can be invaluable when detection of machine abnormalities using human senses is examined. This research outlines the ergonomic issues involved in detecting machine abnormalities and suggests how ergonomics would improve such detections. Cognitive Task Analysis was performed in a plant in Sri Lanka where Total Productive Maintenance is being implemented to identify sensory types that would be used to detect machine abnormalities and relevant Ergonomic characteristics. As the outcome of this research, a methodology comprising of an Ergonomic Gap Analysis Matrix for machine abnormality detection is presented.

  17. Sex chromosome abnormalities and psychiatric diseases

    PubMed Central

    Zhang, Xinzhu; Yang, Jian; Li, Yuhong; Ma, Xin; Li, Rena

    2017-01-01

    Excesses of sex chromosome abnormalities in patients with psychiatric diseases have recently been observed. It remains unclear whether sex chromosome abnormalities are related to sex differences in some psychiatric diseases. While studies showed evidence of susceptibility loci over many sex chromosomal regions related to various mental diseases, others demonstrated that the sex chromosome aneuploidies may be the key to exploring the pathogenesis of psychiatric disease. In this review, we will outline the current evidence on the interaction of sex chromosome abnormalities with schizophrenia, autism, ADHD and mood disorders. PMID:27992373

  18. High Field fMRI Reveals Thalamocortical Integration of Segregated Cognitive and Emotional Processing in Mediodorsal and Intralaminar Thalamic Nuclei

    PubMed Central

    Metzger, C. D.; Eckert, U.; Steiner, J.; Sartorius, A.; Buchmann, J. E.; Stadler, J.; Tempelmann, C.; Speck, O.; Bogerts, B.; Abler, B.; Walter, M.

    2010-01-01

    Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive–emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo–striato–cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing. PMID:21088699

  19. Transient abnormal Q waves during exercise electrocardiography

    PubMed Central

    Alameddine, F F; Zafari, A M

    2004-01-01

    Myocardial ischaemia during exercise electrocardiography is usually manifested by ST segment depression or elevation. Transient abnormal Q waves are rare, as Q waves indicate an old myocardial infarction. The case of a patient with exercise induced transient abnormal Q waves is reported. The potential mechanisms involved in the development of such an abnormality and its clinical implications are discussed. PMID:14676264

  20. [Hysteroscopic polypectomy, treatment of abnormal uterine bleeding].

    PubMed

    de Los Rios, P José F; López, R Claudia; Cifuentes, P Carolina; Angulo, C Mónica; Palacios-Barahona, Arlex U

    2015-07-01

    To evaluate the effectiveness of the hysteroscopic polypectomy in terms of the decrease of the abnormal uterine bleeding. A cross-sectional and analytical study was done with patients to whom a hysteroscopic polypectomy was done for treating the abnormal uterine bleeding, between January 2009 and December 2013. The response to the treatment was evaluated via a survey given to the patients about the behavior of the abnormal uterine bleeding after the procedure and about overall satisfaction. The results were obtained after a hysteroscopic polypectomy done to 128 patients and were as follows. The average time from the polypectomy applied until the survey was 30.5 months, with a standard deviation of 18 months. 67.2% of the patients reported decreased abnormal uterine bleeding and the 32.8% reported a persistence of symptoms. On average 82.8% of the. patients were satisfied with the treatment. Bivariate and multivariate analysis showed no association between the variables studied and no improvement of abnormal uterine bleeding after surgery (polypectomy). There were no complications. Hysteroscopic polypectomy is a safe surgical treatment, which decreases on two of three patients the abnormal uterine bleeding in the presence of endometrial polyps, with an acceptable level of satisfaction.

  1. Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity

    PubMed Central

    Lo, Fu-Sun; Erzurumlu, Reha S.

    2016-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated gene MET tyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAA receptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAA receptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. SIGNIFICANCE STATEMENT A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAA receptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. PMID:27030755

  2. [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.

  3. Clozapine-induced EEG abnormalities and clinical response to clozapine.

    PubMed

    Risby, E D; Epstein, C M; Jewart, R D; Nguyen, B V; Morgan, W N; Risch, S C; Thrivikraman, K V; Lewine, R L

    1995-01-01

    The authors hypothesized that patients who develop gross EEG abnormalities during clozapine treatment would have a less favorable outcome than patients who did not develop abnormal EEGs. The clinical EEGs and the Brief Psychiatric Rating Scale (BPRS) scores of 12 patients with schizophrenia and 4 patients with schizoaffective disorder were compared before and during treatment with clozapine. Eight patients developed significant EEG abnormalities on clozapine; 1 showed worsening of an abnormal pre-clozapine EEG; none of these subjects had clinical seizures. BPRS scores improved significantly in the group of patients who developed abnormal EEGs but not in the group who did not. Findings are consistent with previous reports of a high incidence of clozapine-induced EEG abnormalities and a positive association between these abnormalities and clinical improvement.

  4. 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.

  5. Characterization of Topographically Specific Sleep Spindles in Mice

    PubMed Central

    Kim, Dongwook; Hwang, Eunjin; Lee, Mina; Sung, Hokun; Choi, Jee Hyun

    2015-01-01

    Study Objective: Sleep spindles in humans have been classified as slow anterior and fast posterior spindles; recent findings indicate that their profiles differ according to pharmacology, pathology, and function. However, little is known about the generation mechanisms within the thalamocortical system for different types of spindles. In this study, we aim to investigate the electrophysiological behaviors of the topographically distinctive spindles within the thalamocortical system by applying high-density EEG and simultaneous thalamic LFP recordings in mice. Design: 32-channel extracranial EEG and 2-channel thalamic LFP were recorded simultaneously in freely behaving mice to acquire spindles during spontaneous sleep. Subjects: Hybrid F1 male mice of C57BL/6J and 129S4/svJae. Measurements and Results: Spindle events in each channel were detected by spindle detection algorithm, and then a cluster analysis was applied to classify the topographically distinctive spindles. All sleep spindles were successfully classified into 3 groups: anterior, posterior, and global spindles. Each spindle type showed distinct thalamocortical activity patterns regarding the extent of similarity, phase synchrony, and time lags between cortical and thalamic areas during spindle oscillation. We also found that sleep slow waves were likely to associate with all types of sleep spindles, but also that the ongoing cortical decruitment/recruitment dynamics before the onset of spindles and their relationship with spindle generation were also variable, depending on the spindle types. Conclusion: Topographically specific sleep spindles show distinctive thalamocortical network behaviors. Citation: Kim D, Hwang E, Lee M, Sung H, Choi JH. Characterization of topographically specific sleep spindles in mice. SLEEP 2015;38(1):85–96. PMID:25325451

  6. Abnormal findings in peers during skills learning.

    PubMed

    Wearn, Andy; Nakatsuji, Miriam; Bhoopatkar, Harsh

    2017-02-01

    Peer physical examination (PPE), where students examine each other, is common in contemporary clinical skills learning. A range of benefits and risks have been explored in the literature. One persistent concern has been the identification and management of abnormal physical findings. Two previous studies have attempted to quantify the risk, one through the discussion of two exemplar cases and the other with a retrospective student survey. Here, we report the first prospective study of the number and type of abnormalities encountered as part of early clinical skills learning in a medical programme. We have a formal written consent process for PPE, which includes the management of abnormal findings through the completion of an event form. Our data come from cohorts undertaking years 2 and 3 of the programme between 2003 and 2014. One persistent concern (of PPE) has been the identification and management of abnormal physical findings RESULTS: Nineteen event forms were completed over this period. The incidence rates per year ranged from 0.23 to 1.05 per cent. Abnormal findings included raised blood pressure, heart murmur, abnormal bedside test values, and eye and skin conditions. The low event rate, along with a feasible process for dealing with this issue, goes some way to reassuring those with concerns. We acknowledge that some abnormalities may have been missed, and that some data may have been lost as a result of incorrect process; however, even the highest annual rate is low in absolute terms. We recommend a formal process for managing abnormalities. Ideally this would be part of an overall PPE written policy, communicated to students, enacted by tutors and approved by the local ethics committee. © 2016 John Wiley & Sons Ltd.

  7. Electrocardiogram abnormalities and coronary calcification in postmenopausal women.

    PubMed

    Sabour, Siamak; Grobbee, Diederick; Rutten, Annemarieke; Prokop, Mathias; Bartelink, Marie-Louise; van der Schouw, Yvonne; Bots, Michiel

    2010-01-01

    An electrocardiogram (ECG) can provide information on subclinical myocardial damage. The presence, and more importantly, the quantity of coronary artery calcification (CAC), relates well with the overall severity of the atherosclerotic process. A strong relation has been demonstrated between coronary calcium burden and the incidence of myocardial infarction, a relation independent of age. The aim of this study was to assess the relation of left ventricular hypertrophy (LVH) and ECG abnormalities with CAC. The study population comprised 566 postmenopausal women selected from a population-based cohort study. Information on LVH and repolarization abnormalities (T-axis and QRS-T angle) was obtained using electrocardiography. Modular ECG Analysis System (MEANS) was used to assess ECG abnormalities. The women underwent a multi detector-row computed tomography (MDCT) scan (Philips Mx 8000 IDT 16) to assess CAC. The Agatston score was used to quantify CAC; scores greater than zero were considered as the presence of coronary calcium. Logistic regression was used to assess the relation of ECG abnormality with coronary calcification. LVH was found in 2.7% (n = 15) of the women. The prevalence of T-axis abnormality was 6% (n = 34), whereas 8.5% (n = 48) had a QRS-T angle abnormality. CAC was found in 62% of the women. Compared to women with a normal T-axis, women with borderline or abnormal T-axes were 3.8 fold more likely to have CAC (95% CI: 1.4-10.2). Similarly, compared to women with a normal QRS-T angle, in women with borderline or abnormal QRS-T angle, CAC was 2.0 fold more likely to be present (95% CI: 1.0-4.1). Among women with ECG abnormalities reflecting subclinical ischemia, CAC is commonly found and may in part explain the increased coronary heart disease risk associated with these ECG abnormalities.

  8. Electrocardiogram Abnormalities and Coronary Calcification in Postmenopausal Women

    PubMed Central

    Sabour, Siamak; Grobbee, Diederick; Rutten, Annemarieke; Prokop, Mathias; Bartelink, Marie-Louise; van der Schouw, Yvonne; Bots, Michiel

    2010-01-01

    Background: An electrocardiogram (ECG) can provide information on subclinical myocardial damage. The presence, and more importantly, the quantity of coronary artery calcification (CAC), relates well with the overall severity of the atherosclerotic process. A strong relation has been demonstrated between coronary calcium burden and the incidence of myocardial infarction, a relation independent of age. The aim of this study was to assess the relation of left ventricular hypertrophy (LVH) and ECG abnormalities with CAC. Methods: The study population comprised 566 postmenopausal women selected from a population-based cohort study. Information on LVH and repolarization abnormalities (T-axis and QRS-T angle) was obtained using electrocardiography. Modular ECG Analysis System (MEANS) was used to assess ECG abnormalities. The women underwent a multi detector-row computed tomography (MDCT) scan (Philips Mx 8000 IDT 16) to assess CAC. The Agatston score was used to quantify CAC; scores greater than zero were considered as the presence of coronary calcium. Logistic regression was used to assess the relation of ECG abnormality with coronary calcification. Results: LVH was found in 2.7% (n = 15) of the women. The prevalence of T-axis abnormality was 6% (n = 34), whereas 8.5% (n = 48) had a QRS-T angle abnormality. CAC was found in 62% of the women. Compared to women with a normal T-axis, women with borderline or abnormal T-axes were 3.8 fold more likely to have CAC (95% CI: 1.4–10.2). Similarly, compared to women with a normal QRS-T angle, in women with borderline or abnormal QRS-T angle, CAC was 2.0 fold more likely to be present (95% CI: 1.0–4.1). Conclusion: Among women with ECG abnormalities reflecting subclinical ischemia, CAC is commonly found and may in part explain the increased coronary heart disease risk associated with these ECG abnormalities. PMID:23074563

  9. Intra-Ocular Pressure Measurement in a Patient with a Thin, Thick or Abnormal Cornea.

    PubMed

    Clement, Colin I; Parker, Douglas G A; Goldberg, Ivan

    2016-01-01

    Accurate measurement of intra-ocular pressure is a fundamental component of the ocular examination. The most common method of measuring IOP is by Goldmann applanation tonometry, the accuracy of which is influenced by the thickness and biomechanical properties of the cornea. Algorithms devised to correct for corneal thickness to estimate IOP oversimplify the effects of corneal biomechanics. The viscous and elastic properties of the cornea influence IOP measurements in unpredictable ways, a finding borne out in studies of patients with inherently abnormal and surgically altered corneal biomechanics. Dynamic contour tonometry, rebound tonometry and the ocular response analyzer provide useful alternatives to GAT in patients with abnormal corneas, such as those who have undergone laser vision correction or keratoplasty. This article reviews the various methods of intra-ocular pressure measurement available to the clinician and the ways in which their utility is influenced by variations in corneal thickness and biomechanics.

  10. Classification of breast abnormalities using artificial neural network

    NASA Astrophysics Data System (ADS)

    Zaman, Nur Atiqah Kamarul; Rahman, Wan Eny Zarina Wan Abdul; Jumaat, Abdul Kadir; Yasiran, Siti Salmah

    2015-05-01

    Classification is the process of recognition, differentiation and categorizing objects into groups. Breast abnormalities are calcifications which are tumor markers that indicate the presence of cancer in the breast. The aims of this research are to classify the types of breast abnormalities using artificial neural network (ANN) classifier and to evaluate the accuracy performance using receiver operating characteristics (ROC) curve. The methods used in this research are ANN for breast abnormalities classifications and Canny edge detector as a feature extraction method. Previously the ANN classifier provides only the number of benign and malignant cases without providing information for specific cases. However in this research, the type of abnormality for each image can be obtained. The existing MIAS MiniMammographic database classified the mammogram images into three features only namely characteristic of background tissues, class of abnormality and radius of abnormality. However, in this research three other features are added-in. These three features are number of spots, area and shape of abnormalities. Lastly the performance of the ANN classifier is evaluated using ROC curve. It is found that ANN has an accuracy of 97.9% which is considered acceptable.

  11. Abnormal Selective Attention Normalizes P3 Amplitudes in PDD

    ERIC Educational Resources Information Center

    Hoeksma, Marco R.; Kemner, Chantal; Kenemans, J. Leon; van Engeland, Herman

    2006-01-01

    This paper studied whether abnormal P3 amplitudes in PDD are a corollary of abnormalities in ERP components related to selective attention in visual and auditory tasks. Furthermore, this study sought to clarify possible age differences in such abnormalities. Children with PDD showed smaller P3 amplitudes than controls, but no abnormalities in…

  12. Antipsychotics reverse abnormal EEG complexity in drug-naïve schizophrenia: A multiscale entropy analysis

    PubMed Central

    Takahashi, Tetsuya; Cho, Raymond Y.; Mizuno, Tomoyuki; Kikuchi, Mitsuru; Murata, Tetsuhito; Takahashi, Koichi; Wada, Yuji

    2010-01-01

    Multiscale entropy (MSE) analysis is a novel entropy-based approach for measuring dynamical complexity in physiological systems over a range of temporal scales. To evaluate this analytic approach as an aid to elucidating the pathophysiologic mechanisms in schizophrenia, we examined MSE in EEG activity in drug-naïve schizophrenia subjects pre- and post-treatment with antipsychotics in comparison with traditional EEG analysis. We recorded eyes-closed resting state EEG from frontal, temporal, parietal and occipital regions in drug-naïve 22 schizophrenia and 24 age-matched healthy control subjects. Fifteen patients were re-evaluated within 2–8 weeks after the initiation of antipsychotic treatment. For each participant, MSE was calculated on one continuous 60 second epoch for each experimental session. Schizophrenia subjects showed significantly higher complexity at higher time scales (lower frequencies), than that of healthy controls in fronto-centro-temporal, but not in parieto-occipital regions. Post-treatment, this higher complexity decreased to healthy control subject levels selectively in fronto-central regions, while the increased complexity in temporal sites remained higher. Comparative power analysis identified spectral slowing in frontal regions in pre-treatment schizophrenia subjects, consistent with previous findings, whereas no antipsychotic treatment effect was observed. In summary, multiscale entropy measures identified abnormal dynamical EEG signal complexity in anterior brain areas in schizophrenia that normalized selectively in fronto-central areas with antipsychotic treatment. These findings show that entropy-based analytic methods may serve as a novel approach for characterizing and understanding abnormal cortical dynamics in schizophrenia, and elucidating the therapeutic mechanisms of antipsychotics. PMID:20149880

  13. 42 CFR 37.54 - Notification of abnormal radiographic findings.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other significant abnormal findings... shape or size, tuberculosis, cancer, complicated pneumoconiosis, and any other significant abnormal...

  14. Lenticular abnormalities in children.

    PubMed

    Khokhar, Sudarshan; Agarwal, Tushar; Kumar, Gaurav; Kushmesh, Rakhi; Tejwani, Lalit Kumar

    2012-01-01

    To study the lenticular problems in children presenting at an apex institute. Retrospective analysis of records (< 14 years) of new lens clinic cases was done. Of 1,047 children, 687 were males. Mean age at presentation was 6.35 ± 4.13 years. Developmental cataract was seen in 45.6% and posttraumatic cataract in 29.7% of patients. Other abnormalities were cataract with retinal detachment, persistent hyperplastic primary vitreous, subluxated lens, micro/spherophakia, cataract secondary to uveitis, intraocular lens complications, cataract with choroidal coloboma, and visual axis opacification. Developmental and posttraumatic cataracts were the most common abnormalities. Delayed presentation is of concern. Copyright 2012, SLACK Incorporated.

  15. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  16. Impaired coupling of local and global functional feedbacks underlies abnormal synchronization and negative symptoms of schizophrenia.

    PubMed

    Noh, Kyungchul; Shin, Kyung Soon; Shin, Dongkwan; Hwang, Jae Yeon; Kim, June Sic; Jang, Joon Hwan; Chung, Chun Kee; Kwon, Jun Soo; Cho, Kwang-Hyun

    2013-04-10

    Abnormal synchronization of brain oscillations is found to be associated with various core symptoms of schizophrenia. However, the underlying mechanism of this association remains yet to be elucidated. In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia. Analysis of the magnetoencephalography data obtained from patients with chronic schizophrenia during rest revealed an increase in beta band synchronization and a reduction in gamma band power compared to healthy controls. Using a feedback identification method based on non-causal impulse responses, we constructed functional feedback networks and found that CLGF circuits were significantly reduced in schizophrenia. From computational analysis on the basis of the Wilson-Cowan model, we unraveled that the CLGF circuits are critically involved in the abnormal synchronization and the dynamical switching between beta and gamma bands power in schizophrenia. Moreover, we found that the abundance of CLGF circuits was negatively correlated with the development of negative symptoms of schizophrenia, suggesting that the negative symptom is closely related to the impairment of this circuit. Our study implicates that patients with schizophrenia might have the impaired coupling of inter- and intra-regional functional feedbacks and that the CLGF circuit might serve as a critical bridge between abnormal synchronization and the negative symptoms of schizophrenia.

  17. Abnormal placentation.

    PubMed

    Bauer, Samuel T; Bonanno, Clarissa

    2009-04-01

    Abnormal placentation poses a diagnostic and treatment challenge for all providers caring for pregnant women. As one of the leading causes of postpartum hemorrhage, abnormal placentation involves the attachment of placental villi directly to the myometrium with potentially deeper invasion into the uterine wall or surrounding organs. Surgical procedures that disrupt the integrity of uterus, including cesarean section, dilatation and curettage, and myomectomy, have been implicated as key risk factors for placenta accreta. The diagnosis is typically made by gray-scale ultrasound and confirmed with magnetic resonance imaging, which may better delineate the extent of placental invasion. It is critical to make the diagnosis before delivery because preoperative planning can significantly decrease blood loss and avoid substantial morbidity associated with placenta accreta. Aggressive management of hemorrhage through the use of uterotonics, fluid resuscitation, blood products, planned hysterectomy, and surgical hemostatic agents can be life-saving for these patients. Conservative management, including the use of uterine and placental preservation and subsequent methotrexate therapy or pelvic artery embolization, may be considered when a focal accreta is suspected; however, surgical management remains the current standard of care.

  18. Acute effect of carbamazepine on corticothalamic 5-9-Hz and thalamocortical spindle (10-16-Hz) oscillations in the rat.

    PubMed

    Zheng, Thomas W; O'Brien, Terence J; Kulikova, Sofya P; Reid, Christopher A; Morris, Margaret J; Pinault, Didier

    2014-03-01

    A major side effect of carbamazepine (CBZ), a drug used to treat neurological and neuropsychiatric disorders, is drowsiness, a state characterized by increased slow-wave oscillations with the emergence of sleep spindles in the electroencephalogram (EEG). We conducted cortical EEG and thalamic cellular recordings in freely moving or lightly anesthetized rats to explore the impact of CBZ within the intact corticothalamic (CT)-thalamocortical (TC) network, more specifically on CT 5-9-Hz and TC spindle (10-16-Hz) oscillations. Two to three successive 5-9-Hz waves were followed by a spindle in the cortical EEG. A single systemic injection of CBZ (20 mg/kg) induced a significant increase in the power of EEG 5-9-Hz oscillations and spindles. Intracellular recordings of glutamatergic TC neurons revealed 5-9-Hz depolarizing wave-hyperpolarizing wave sequences prolonged by robust, rhythmic spindle-frequency hyperpolarizing waves. This hybrid sequence occurred during a slow hyperpolarizing trough, and was at least 10 times more frequent under the CBZ condition than under the control condition. The hyperpolarizing waves reversed at approximately -70 mV, and became depolarizing when recorded with KCl-filled intracellular micropipettes, indicating that they were GABAA receptor-mediated potentials. In neurons of the GABAergic thalamic reticular nucleus, the principal source of TC GABAergic inputs, CBZ augmented both the number and the duration of sequences of rhythmic spindle-frequency bursts of action potentials. This indicates that these GABAergic neurons are responsible for the generation of at least the spindle-frequency hyperpolarizing waves in TC neurons. In conclusion, CBZ potentiates GABAA receptor-mediated TC spindle oscillations. Furthermore, we propose that CT 5-9-Hz waves can trigger TC spindles. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. 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.

  20. 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.

  1. Four families with immunodeficiency and chromosome abnormalities.

    PubMed Central

    Candy, D C; Hayward, A R; Hughes, D T; Layward, L; Soothill, J F

    1979-01-01

    Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two. Images Fig. 1 Fig. 3 PMID:314782

  2. Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography.

    PubMed

    Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi

    2017-01-01

    There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34-40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI

  3. Convergence of Cortical, Thalamocortical, and Callosal Pathways during Human Fetal Development Revealed by Diffusion MRI Tractography

    PubMed Central

    Wang, Rongpin; Wilkinson, Molly; Kane, Tara; Takahashi, Emi

    2017-01-01

    There has been evidence that during brain development, emerging thalamocortical (TC) and corticothalamic (CT) pathways converge in some brain regions and follow each other's trajectories to their final destinations. Corpus callosal (CC) pathways also emerge at a similar developmental stage, and are known to converge with TC pathways in specific cortical regions in mature brains. Given the functional relationships between TC and CC pathways, anatomical convergence of the two pathways are likely important for their functional integration. However, it is unknown (1) where TC and CT subcortically converge in the human brain, and (2) where TC and CC converge in the cortex of the human brain, due to the limitations of non-invasive methods. The goals of this study were to describe the spatio-temporal relationships in the development of the TC/CT and CC pathways in the human brain, using high-angular resolution diffusion MR imaging (HARDI) tractography. Emerging cortical, TC and CC pathways were identified in postmortem fetal brains ranging from 17 gestational weeks (GW) to 30 GW, as well as in vivo 34–40 GW newborns. Some pathways from the thalami were found to be converged with pathways from the cerebral cortex as early as 17 GW. Such convergence was observed mainly in anterior and middle regions of the brain until 21 GW. At 22 GW and onwards, posterior pathways from the thalami also converged with cortical pathways. Many CC pathways reached the full length up to the cortical surface as early as 17 GW, while pathways linked to thalami (not only TC axons but also including pathways linked to thalamic neuronal migration) reached the cortical surface at and after 20 GW. These results suggest that CC pathways developed earlier than the TC pathways. The two pathways were widespread at early stages, but by 40 GW they condensed and formed groups of pathways that projected to specific regions of the cortex and overlapped in some brain regions. These results suggest that HARDI

  4. Identification of abnormal accident patterns at intersections

    DOT National Transportation Integrated Search

    1999-08-01

    This report presents the findings and recommendations based on the Identification of Abnormal Accident Patterns at Intersections. This project used a statistically valid sampling method to determine whether a specific intersection has an abnormally h...

  5. Chronic radiation exposure modifies temporal dynamics of cytogenetic but not reproductive indicators in Scots pine populations.

    PubMed

    Geras'kin, Stanislav; Oudalova, Alla; Kuzmenkov, Alexey; Vasiliyev, Denis

    2018-04-18

    Over a period of 13 years (2003-2015), reproductive and cytogenetic effects are investigated in Scots pine populations growing in the Bryansk region of Russia radioactively contaminated as a result of the Chernobyl accident. In reference populations, the frequencies of cytogenetic abnormalities are shown to change with time in a cyclic manner. In chronically exposed populations, the cyclic patterns in temporal dynamics of cytogenetic abnormalities appear to be disturbed. In addition, a tendency to decrease in the frequencies of cytogenetic abnormalities with time as well as an increase in their variability with dose rate is revealed. In contrast, no significant impact of chronic radiation exposure on the time dynamics of reproductive indexes is detected. Finally, long-term observations on chronically exposed Scots pine populations revealed qualitative differences in the temporal dynamics of reproductive and cytogenetic indicators. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. 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.

  7. Genetics Home Reference: X-linked lissencephaly with abnormal genitalia

    MedlinePlus

    ... Health Conditions X-linked lissencephaly with abnormal genitalia X-linked lissencephaly with abnormal genitalia Printable PDF Open ... Javascript to view the expand/collapse boxes. Description X-linked lissencephaly with abnormal genitalia (XLAG) is a ...

  8. High lifetime probability of screen-detected cervical abnormalities.

    PubMed

    Pankakoski, Maiju; Heinävaara, Sirpa; Sarkeala, Tytti; Anttila, Ahti

    2017-12-01

    Objective Regular screening and follow-up is an important key to cervical cancer prevention; however, screening inevitably detects mild or borderline abnormalities that would never progress to a more severe stage. We analysed the cumulative probability and recurrence of cervical abnormalities in the Finnish organized screening programme during a 22-year follow-up. Methods Screening histories were collected for 364,487 women born between 1950 and 1965. Data consisted of 1 207,017 routine screens and 88,143 follow-up screens between 1991 and 2012. Probabilities of cervical abnormalities by age were estimated using logistic regression and generalized estimating equations methodology. Results The probability of experiencing any abnormality at least once at ages 30-64 was 34.0% (95% confidence interval [CI]: 33.3-34.6%) . Probability was 5.4% (95% CI: 5.0-5.8%) for results warranting referral and 2.2% (95% CI: 2.0-2.4%) for results with histologically confirmed findings. Previous occurrences were associated with an increased risk of detecting new ones, specifically in older women. Conclusion A considerable proportion of women experience at least one abnormal screening result during their lifetime, and yet very few eventually develop an actual precancerous lesion. Re-evaluation of diagnostic criteria concerning mild abnormalities might improve the balance of harms and benefits of screening. Special monitoring of women with recurrent abnormalities especially at older ages may also be needed.

  9. [Abnormal cervicovaginal cytology in women with rheumatoid arthritis].

    PubMed

    Mercado, Ulises

    2010-02-01

    Patients with rheumatoid arthritis (RA) are at increased risk of infections and cancer. A link between RA and abnormal cervicovaginal cytology has rarely been reported. The aim of this study was to review cervicovaginal cytology results in women with RA and compare them with a control population. Sexual behavior also was investigated. Cervicovaginal cytology results of 95 women with RA were compared to those of a control population of 1,719 women attending at the same hospital and followed until June 2009. Records of RA patients were reviewed to obtain clinical data, particularly sexual behavior. Of 95 RA patients, 13/95 had an abnormal cervicovaginal cytology result, compared with 120/1,719 controls. Twelve/13 had squamous intraepithelial lesions (SIL), compared with 27/120 controls. There was no significant difference in sexual partners between women with RA and controls. Women with RA without abnormal cervicovaginal cytology had less sexual partners than those with RA and abnormal cytology. Two women with RA and abnormal cervicovaginal cytology had a history of condylomata and herpes genital. Three/13 women with RA developed abnormal cervicovaginal cytology after 12 to 36 months initiating their illness. None from them had ever received immunosuppressants. Women with RA have an increased prevalence of abnormal cervical cytology, compared with a control population. It may be related to chronic inflammatory disease and sexual behavior.

  10. Defective mitochondrial dynamics is an early event in skeletal muscle of an amyotrophic lateral sclerosis mouse model.

    PubMed

    Luo, Guo; Yi, Jianxun; Ma, Changling; Xiao, Yajuan; Yi, Frank; Yu, Tian; Zhou, Jingsong

    2013-01-01

    Mitochondria are dynamic organelles that constantly undergo fusion and fission to maintain their normal functionality. Impairment of mitochondrial dynamics is implicated in various neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is an adult-onset neuromuscular degenerative disorder characterized by motor neuron death and muscle atrophy. ALS onset and progression clearly involve motor neuron degeneration but accumulating evidence suggests primary muscle pathology may also be involved. Here, we examined mitochondrial dynamics in live skeletal muscle of an ALS mouse model (G93A) harboring a superoxide dismutase mutation (SOD1(G93A)). Using confocal microscopy combined with overexpression of mitochondria-targeted photoactivatable fluorescent proteins, we discovered abnormal mitochondrial dynamics in skeletal muscle of young G93A mice before disease onset. We further demonstrated that similar abnormalities in mitochondrial dynamics were induced by overexpression of mutant SOD1(G93A) in skeletal muscle of normal mice, indicating the SOD1 mutation drives ALS-like muscle pathology in the absence of motor neuron degeneration. Mutant SOD1(G93A) forms aggregates inside muscle mitochondria and leads to fragmentation of the mitochondrial network as well as mitochondrial depolarization. Partial depolarization of mitochondrial membrane potential in normal muscle by carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) caused abnormalities in mitochondrial dynamics similar to that in the SOD1(G93A) model muscle. A specific mitochondrial fission inhibitor (Mdivi-1) reversed the SOD1(G93A) action on mitochondrial dynamics, indicating SOD1(G93A) likely promotes mitochondrial fission process. Our results suggest that accumulation of mutant SOD1(G93A) inside mitochondria, depolarization of mitochondrial membrane potential and abnormal mitochondrial dynamics are causally linked and cause intrinsic muscle pathology, which occurs early in the course of ALS and may

  11. Abnormalities of High Density Lipoproteins in Abetalipoproteinemia*

    PubMed Central

    Jones, John W.; Ways, Peter

    1967-01-01

    Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts. 2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states. The available evidence suggests that the abnormally low levels of HDL3 and the deranged phospholipid distribution are more specific for abetalipoproteinemia than the fatty acid abnormalities. However, the absence of these abnormalities in obligate heterozygous subjects makes their relationship to the primary defect of abetalipoproteinemia difficult to assess. Images PMID:6027078

  12. 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.

  13. Endocrine abnormalities in lithium toxicity.

    PubMed

    Shanks, Gabriella; Mishra, Vinita; Nikolova, Stanka

    2017-10-01

    Lithium toxicity can manifest as a variety of biochemical -abnormalities. This case report describes a patient -presenting to the emergency department with neuropsychiatric -symptoms on a background of bipolar disorder, for which she was prescribed lithium for 26 years previously. Cases of lithium toxicity are rare but can be severe and this case report -demonstrates to clinicians that they must be thorough in investigating patients with lithium toxicity, as there are many potential abnormalities that can manifest concurrently. © Royal College of Physicians 2017. All rights reserved.

  14. Neural Darwinism and consciousness.

    PubMed

    Seth, Anil K; Baars, Bernard J

    2005-03-01

    Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the 'dynamic core'). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well.

  15. Brain and bone abnormalities of thanatophoric dwarfism.

    PubMed

    Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa

    2009-01-01

    The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.

  16. 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

  17. Sex-specific hip osteoarthritis-associated gait abnormalities: Alterations in dynamic hip abductor function differ in men and women.

    PubMed

    Foucher, Kharma C

    2017-10-01

    Hip osteoarthritis results in abnormal gait mechanics, but it is not known whether abnormalities are the same in men and women. The hypothesis tested was that gait abnormalities are different in men and women with hip osteoarthritis vs. sex-specific asymptomatic groups. 150 subjects with mild through severe radiographic hip osteoarthritis and 159 asymptomatic subjects were identified from an Institutional Review Board-approved motion analysis data repository. Sagittal plane hip range of motion and peak external moments about the hip, in all three planes, averaged from normal speed walking trials, were compared for men and women, with and without hip osteoarthritis using analysis of variance. There were significant sex by group interactions for the external peak hip adduction and external rotation moments (P=0.009-0.045). Although asymptomatic women had peak adduction and external rotation moments that were respectively 12% higher and 23% lower than asymptomatic men (P=0.026-0.037), these variables did not differ between men and women with hip osteoarthritis (P≥0.684). The osteoarthritis vs. asymptomatic group difference in the peak hip adduction moment was 45% larger in women than in men. The osteoarthritis vs. asymptomatic group difference in the peak hip external rotation moment was 55% larger for men than for women (P<0.001). Sex did not influence the association between radiographic severity and gait variables. Normal sex differences in gait were not seen in hip osteoarthritis. Sex-specific adaptations may reflect different aspects of hip abductor function. Men and women with hip osteoarthritis may require different interventions to improve function. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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

  19. Prevention of congenital abnormalities by periconceptional multivitamin supplementation.

    PubMed Central

    Czeizel, A E

    1993-01-01

    OBJECTIVE--To study the effect of periconceptional multivitamin supplementation on neural tube defects and other congenital abnormality entities. DESIGN--Randomised controlled trial of supplementation with multivitamins and trace elements. SETTING--Hungarian family planning programme. SUBJECTS--4156 pregnancies with known outcome and 3713 infants evaluated in the eighth month of life. INTERVENTIONS--A single tablet of a multivitamin including 0.8 mg of folic acid or trace elements supplement daily for at least one month before conception and at least two months after conception. MAIN OUTCOME MEASURES--Number of major and mild congenital abnormalities. RESULTS--The rate of all major congenital abnormalities was significantly lower in the group given vitamins than in the group given trace elements and this difference cannot be explained totally by the significant reduction of neural tube defects. The rate of major congenital abnormalities other than neural tube defects and genetic syndromes was 9.0/1000 in pregnancies with known outcome in the vitamin group and 16.6/1000 in the trace element group; relative risk 1.85 (95% confidence interval 1.02 to 3.38); difference, 7.6/1000. The rate of all major congenital abnormalities other than neural tube defects and genetic syndromes diagnosed up to the eighth month of life was 14.7/1000 informative pregnancies in the vitamin group and 28.3/1000 in the trace element group; relative risk 1.95 (1.23 to 3.09); difference, 13.6/1000. The rate of some congenital abnormalities was lower in the vitamin group than in the trace element group but the differences for each group of abnormalities were not significant. CONCLUSIONS--Periconceptional multivitamin supplementation can reduce not only the rate of neural tube defects but also the rate of other major non-genetic syndromatic congenital abnormalities. Further studies are needed to differentiate the chance effect and vitamin dependent effect. PMID:8324432

  20. Sleep EEG Fingerprints Reveal Accelerated Thalamocortical Oscillatory Dynamics in Williams Syndrome

    ERIC Educational Resources Information Center

    Bodizs, Robert; Gombos, Ferenc; Kovacs, Ilona

    2012-01-01

    Sleep EEG alterations are emerging features of several developmental disabilities, but detailed quantitative EEG data on the sleep phenotype of patients with Williams syndrome (WS, 7q11.23 microdeletion) is still lacking. Based on laboratory (Study I) and home sleep records (Study II) here we report WS-related features of the patterns of…

  1. Retinal abnormalities in β-thalassemia major

    PubMed Central

    Bhoiwala, Devang L.; Dunaief, Joshua L.

    2015-01-01

    Patients with beta (β)-thalassemia (β-TM: thalassemia major, β-TI: thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelium degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-TM are transfusion dependent and require iron chelation therapy (ICT) in order to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by ICT. Some who were never treated with ICT exhibited retinopathy, and others receiving ICT had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-TM viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202

  2. Neurological abnormalities associated with CDMA exposure.

    PubMed

    Hocking, B; Westerman, R

    2001-09-01

    Dysaesthesiae of the scalp and neurological abnormality after mobile phone use have been reported previously, but the roles of the phone per se or the radiations in causing these findings have been questioned. We report finding a neurological abnormality in a patient after accidental exposure of the left side of the face to mobile phone radiation [code division multiple access (CDMA)] from a down-powered mobile phone base station antenna. He had headaches, unilateral left blurred vision and pupil constriction, unilateral altered sensation on the forehead, and abnormalities of current perception thresholds on testing the left trigeminal ophthalmic nerve. His nerve function recovered during 6 months follow-up. His exposure was 0.015-0.06 mW/cm(2) over 1-2 h. The implications regarding health effects of radiofrequency radiation are discussed.

  3. Sleep Physiology, Abnormal States, and Therapeutic Interventions

    PubMed Central

    Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

    2012-01-01

    Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

  4. Dynamic Resting-State Functional Connectivity in Major Depression.

    PubMed

    Kaiser, Roselinde H; Whitfield-Gabrieli, Susan; Dillon, Daniel G; Goer, Franziska; Beltzer, Miranda; Minkel, Jared; Smoski, Moria; Dichter, Gabriel; Pizzagalli, Diego A

    2016-06-01

    Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.

  5. [Liver enzyme abnormalities among oil refinery workers].

    PubMed

    Carvalho, Fernando Martins; Silvany Neto, Annibal Muniz; Mendes, João Luiz Barberino; Cotrim, Helma Pinchemel; Nascimento, Ana Lísia Cunha; Lima Júnior, Alberto Soares; Cunha, Tatiana Oliveira Bernardo da

    2006-02-01

    Occupational exposure typical of an oil refinery may alter liver function among the workers. Thus, the objective of the study was to identify risk factors for liver enzyme abnormalities among oil refinery workers. The workers at an oil refinery in Northeastern Brazil underwent routine annual medical examination from 1982 to 1998. This case-control study investigated all the 150 cases of individuals with simultaneous gamma-glutamyltransferase and alanine aminotransferase abnormalities of at least 10% above reference levels. As controls, 150 workers without any liver enzyme or bilirubin abnormalities since starting to work there were selected. Odds ratios and the respective 95% confidence intervals were calculated from logistic regression models. In all the production sectors, the risk of liver enzyme abnormalities was significantly higher than in the administrative sector (OR=5.7; 95% CI: 1.7-18.4), even when the effects of alcohol, obesity and medical history of hepatitis were controlled for. During the period from 1992 to 1994, 88 out of the 89 cases occurred among workers from the various production sectors. Occupational exposure plays an important role in causing liver enzyme abnormalities among oil refinery workers. This is in addition to the specifically biological and/or behavioral risk factors such as obesity and alcohol consumption.

  6. Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

    PubMed

    Lo, Fu-Sun; Erzurumlu, Reha S; Powell, Elizabeth M

    2016-03-30

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis. A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention. Copyright © 2016 the authors 0270-6474/16/363691-07$15.00/0.

  7. The prevalence of chromosomal abnormalities in subgroups of infertile men.

    PubMed

    Dul, E C; Groen, H; van Ravenswaaij-Arts, C M A; Dijkhuizen, T; van Echten-Arends, J; Land, J A

    2012-01-01

    The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men. In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities. The prevalence of chromosomal abnormalities in the cohort was 3.1%. No association was found between chromosomal abnormalities and sperm volume, concentration, progressive motility or total motile sperm count. Azoospermia was significantly associated with the presence of a chromosomal abnormality [15.2%, odds ratio (OR) 7.70, P < 0.001]. High gonadotrophin levels were also associated with an increased prevalence of chromosomal abnormalities (OR 2.96, P = 0.013). Azoospermic men with a positive andrologic history had a lower prevalence of chromosomal abnormalities than azoospermic men with an uneventful history (OR 0.28, P = 0.047). In non-azoospermic men, we found that none of the studied variables were associated with the prevalence of chromosomal abnormalities. We show that the highest prevalence of chromosomal abnormalities is found in hypergonadotrophic azoospermic men with an uneventful andrologic history.

  8. Abnormal/Emergency Situations. Impact of Unmanned Aircraft Systems Emergency and Abnormal Events on the National Airspace System

    NASA Technical Reports Server (NTRS)

    2006-01-01

    Access 5 analyzed the differences between UAS and manned aircraft operations under five categories of abnormal or emergency situations: Link Failure, Lost Communications, Onboard System Failures, Control Station Failures and Abnormal Weather. These analyses were made from the vantage point of the impact that these operations have on the US air traffic control system, with recommendations for new policies and procedures included where appropriate.

  9. GABA receptors and T-type Ca2+ channels crosstalk in thalamic networks.

    PubMed

    Leresche, Nathalie; Lambert, Régis C

    2017-06-07

    Although the thalamus presents a rather limited repertoire of GABAergic cell types compare to other CNS area, this structure is a privileged system to study how GABA impacts neuronal network excitability. Indeed both glutamatergic thalamocortical (TC) and GABAergic nucleus reticularis thalami (NRT) neurons present a high expression of T-type voltage-dependent Ca 2+ channels whose activation that shapes the output of the thalamus critically depends upon a preceding hyperpolarisation. Because of this strict dependence, a tight functional link between GABA mediated hyperpolarization and T-currents characterizes the thalamic network excitability. In this review we summarize a number of studies showing that the relationships between the various thalamic GABA A/B receptors and T-channels are complex and bidirectional. We discuss how this dynamic interaction sets the global intrathalamic network activity and its long-term plasticity and highlight how the functional relationship between GABA release and T-channel-dependent excitability is finely tuned by the T-channel activation itself. Finally, we illustrate how an impaired balance between T-channels and GABA receptors can lead to pathologically abnormal cellular and network behaviours. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Dynamic-focusing microscope objective for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Murali, Supraja; Rolland, Jannick

    2007-01-01

    Optical Coherence Tomography (OCT) is a novel optical imaging technique that has assumed significant importance in bio-medical imaging in the last two decades because it is non-invasive and provides accurate, high resolution images of three dimensional cross-sections of body tissue, exceeding the capabilities of the current predominant imaging technique - ultrasound. In this paper, the application of high resolution OCT, known as optical coherence microscopy (OCM) is investigated for in vivo detection of abnormal skin pathology for the early diagnosis of cancer. A main challenge in OCM is maintaining invariant resolution throughout the sample. The technology presented is based on a dynamic focusing microscope imaging probe conceived for skin imaging and the detection of abnormalities in the epithelium. A novel method for dynamic focusing in the biological sample is presented using variable-focus lens technology to obtain three dimensional images with invariant resolution throughout the cross-section and depth of the sample is presented and discussed. A low coherence broadband source centered at near IR wavelengths is used to illuminate the sample. The design, analysis and predicted performance of the dynamic focusing microscope objective designed for dynamic three dimensional imaging at 5μm resolution for the chosen broadband spectrum is presented.

  11. Analysis of the dynamic avalanche of carrier stored trench bipolar transistor (CSTBT) during clamped inductive turn-off transient

    NASA Astrophysics Data System (ADS)

    Xue, Peng; Fu, Guicui

    2017-03-01

    The dynamic avalanche has a huge impact on the switching robustness of carrier stored trench bipolar transistor (CSTBT). The purpose of this work is to investigate the CSTBT's dynamic avalanche mechanism during clamped inductive turn-off transient. At first, with a Mitsubishi 600 V/150 A CSTBT and a Infineon 600 V/200 A field stop insulated gate bipolar transistor (FS-IGBT) utilized, the clamped inductive turn-off characteristics are obtained by double pulse test. The unclamped inductive switching (UIS) test is also utilized to identify the CSTBT's clamping voltage under dynamic avalanche condition. After the test data analysis, it is found that the CSTBT's dynamic avalanche is abnormal and can be triggered under much looser condition than the conventional buffer layer IGBT. The comparison between the FS-IGBT and CSTBT's experimental results implies that the CSTBT's abnormal dynamic avalanche phenomenon may be induced by the carrier storage (CS) layer. Based on the semiconductor physics, the electric field distribution and dynamic avalanche generation in the depletion region are analyzed. The analysis confirms that the CS layer is the root cause of the CSTBT's abnormal dynamic avalanche mechanism. Moreover, the CSTBT's negative gate capacitance effect is also investigated to clarify the underlying mechanism of the gate voltage bump observed in the test. In the end, the mixed-mode numerical simulation is utilized to reproduce the CSTBT's dynamic avalanche behavior. The simulation results validate the proposed dynamic avalanche mechanisms.

  12. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  13. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards). [45 FR 60618, Sept. 12, 1980] ...

  14. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864... hemoglobin assay. (a) Identification. An abnormal hemoglobin assay is a device consisting of the reagents... hemoglobin types. (b) Classification. Class II (performance standards). [45 FR 60618, Sept. 12, 1980] ...

  15. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415 Abnormal...

  16. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415 Abnormal...

  17. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415 Abnormal...

  18. Abnormal carbene-silicon halide complexes.

    PubMed

    Wang, Yuzhong; Xie, Yaoming; Wei, Pingrong; Schaefer, Henry F; Robinson, Gregory H

    2016-04-14

    Reaction of the anionic N-heterocyclic dicarbene (NHDC), [:C{[N(2,6-Pr(i)2C6H3)]2CHCLi}]n (1), with SiCl4 gives the trichlorosilyl-substituted (at the C4 carbon) N-heterocyclic carbene complex (7). Abnormal carbene-SiCl4 complex (8) may be conveniently synthesized by combining 7 with HCl·NEt3. In addition, 7 may react with CH2Cl2 in warm hexane, giving the abnormal carbene-complexed SiCl3(+) cation (9). The nature of the bonding in 9 was probed with complementary DFT computations.

  19. Diverticular Disease of the Colon: Neuromuscular Function Abnormalities.

    PubMed

    Bassotti, Gabrio; Villanacci, Vincenzo; Bernardini, Nunzia; Dore, Maria P

    2016-10-01

    Colonic diverticular disease is a frequent finding in daily clinical practice. However, its pathophysiological mechanisms are largely unknown. This condition is likely the result of several concomitant factors occurring together to cause anatomic and functional abnormalities, leading as a result to the outpouching of the colonic mucosa. A pivotal role seems to be played by an abnormal colonic neuromuscular function, as shown repeatedly in these patients, and by an altered visceral perception. There is recent evidence that these abnormalities might be related to the derangement of the enteric innervation, to an abnormal distribution of mucosal neuropeptides, and to low-grade mucosal inflammation. The latter might be responsible for the development of visceral hypersensitivity, often causing abdominal pain in a subset of these patients.

  20. Abnormal Uterine Bleeding.

    PubMed

    Benetti-Pinto, Cristina Laguna; Rosa-E-Silva, Ana Carolina Japur de Sá; Yela, Daniela Angerame; Soares Júnior, José Maria

    2017-07-01

    Abnormal uterine bleeding is a frequent condition in Gynecology. It may impact physical, emotional sexual and professional aspects of the lives of women, impairing their quality of life. In cases of acute and severe bleeding, women may need urgent treatment with volumetric replacement and prescription of hemostatic substances. In some specific cases with more intense and prolonged bleeding, surgical treatment may be necessary. The objective of this chapter is to describe the main evidence on the treatment of women with abnormal uterine bleeding, both acute and chronic. Didactically, the treatment options were based on the current International Federation of Gynecology and Obstetrics (FIGO) classification system (PALM-COEIN). The etiologies of PALM-COEIN are: uterine Polyp (P), Adenomyosis (A), Leiomyoma (L), precursor and Malignant lesions of the uterine body (M), Coagulopathies (C), Ovulatory dysfunction (O), Endometrial dysfunction (E), Iatrogenic (I), and Not yet classified (N). The articles were selected according to the recommendation grades of the PubMed, Cochrane and Embase databases, and those in which the main objective was the reduction of uterine menstrual bleeding were included. Only studies written in English were included. All editorial or complete papers that were not consistent with abnormal uterine bleeding, or studies in animal models, were excluded. The main objective of the treatment is the reduction of menstrual flow and morbidity and the improvement of quality of life. It is important to emphasize that the treatment in the acute phase aims to hemodynamically stabilize the patient and stop excessive bleeding, while the treatment in the chronic phase is based on correcting menstrual dysfunction according to its etiology and clinical manifestations. The treatment may be surgical or pharmacological, and the latter is based mainly on hormonal therapy, anti-inflammatory drugs and antifibrinolytics. Thieme Revinter Publicações Ltda Rio de Janeiro

  1. Abnormal global and local event detection in compressive sensing domain

    NASA Astrophysics Data System (ADS)

    Wang, Tian; Qiao, Meina; Chen, Jie; Wang, Chuanyun; Zhang, Wenjia; Snoussi, Hichem

    2018-05-01

    Abnormal event detection, also known as anomaly detection, is one challenging task in security video surveillance. It is important to develop effective and robust movement representation models for global and local abnormal event detection to fight against factors such as occlusion and illumination change. In this paper, a new algorithm is proposed. It can locate the abnormal events on one frame, and detect the global abnormal frame. The proposed algorithm employs a sparse measurement matrix designed to represent the movement feature based on optical flow efficiently. Then, the abnormal detection mission is constructed as a one-class classification task via merely learning from the training normal samples. Experiments demonstrate that our algorithm performs well on the benchmark abnormal detection datasets against state-of-the-art methods.

  2. Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease.

    PubMed

    DeLong, Mahlon R; Wichmann, Thomas

    2015-11-01

    The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders. To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example. A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders. The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets. Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with

  3. Metabolic differentiation and classification of abnormal Savda Munziq's pharmacodynamic role on rat models with different diseases by nuclear magnetic resonance-based metabonomics.

    PubMed

    Mamtimin, Batur; Xia, Guo; Mijit, Mahmut; Hizbulla, Mawlanjan; Kurbantay, Nazuk; You, Li; Upur, Halmurat

    2015-01-01

    Abnormal Savda Munziq (ASMq) is a traditional Uyghur herbal preparation used as a therapy for abnormal Savda-related diseases. In this study, we investigate ASMq's dynamic effects on abnormal Savda rat models under different disease conditions. Abnormal Savda rat models with hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), and asthma dosed of ASMq. Serum samples of each animal tested by nuclear magnetic resonance spectroscopy and analyzed by orthogonal projection to latent structure with discriminant analysis. Compared with healthy controls, HCC rats had higher concentrations of amino acids, fat-related metabolites, lactate, myoinositol, and citrate, but lower concentrations of α-glucose, β-glucose, and glutamine. Following ASMq treatment, the serum acetone very low-density lipoprotein (VLDL), LDL, unsaturated lipids, acetylcysteine, and pyruvate concentration decreased, but α-glucose, β-glucose, and glutamine concentration increased (P < 0.05). T2DM rats had higher concentrations of α- and β-glucose, but lower concentrations of isoleucine, leucine, valine, glutamine, glycoprotein, lactate, tyrosine, creatine, alanine, carnitine, and phenylalanine. After ASMq treated T2DM groups showed reduced α- and β-glucose and increased creatine levels (P < 0.05). Asthma rats had higher acetate, carnitine, formate, and phenylalanine levels, but lower concentrations of glutamine, glycoprotein, lactate, VLDL, LDL, and unsaturated lipids. ASMq treatment showed increased glutamine and reduced carnitine, glycoprotein, formate, and phenylalanine levels (P < 0.05). Low immune function, decreased oxidative defense, liver function abnormalities, amino acid deficiencies, and energy metabolism disorders are common characteristics of abnormal Savda-related diseases. ASMq may improve the abnormal metabolism and immune function of rat models with different diseases combined abnormal Savda.

  4. 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.

  5. Salivary glands abnormalities in oculo-auriculo-vertebral spectrum.

    PubMed

    Brotto, Davide; Manara, Renzo; Vio, Stefania; Ghiselli, Sara; Cantone, Elena; Mardari, Rodica; Toldo, Irene; Stritoni, Valentina; Castiglione, Alessandro; Lovo, Elisa; Trevisi, Patrizia; Bovo, Roberto; Martini, Alessandro

    2018-01-01

    Feeding and swallowing impairment are present in up to 80% of oculo-auriculo-vertebral spectrum (OAVS) patients. Salivary gland abnormalities have been reported in OAVS patients but their rate, features, and relationship with phenotype severity have yet to be defined. Parotid and submandibular salivary gland hypo/aplasia was evaluated on head MRI of 25 OAVS patients (16 with severe phenotype, Goldenhar syndrome) and 11 controls. All controls disclosed normal salivary glands. Abnormal parotid glands were found exclusively ipsilateral to facial microsomia in 21/25 OAVS patients (84%, aplasia in six patients) and showed no association with phenotype severity (14/16 patients with Goldenhar phenotype vs 7/9 patients with milder phenotype, p = 0.6). Submandibular salivary gland hypoplasia was detected in six OAVS patients, all with concomitant ipsilateral severe involvement of the parotid gland (p < 0.001). Submandibular salivary gland hypoplasia was associated to Goldenhar phenotype (p < 0.05). Parotid gland abnormalities were associated with ipsilateral fifth (p < 0.001) and seventh cranial nerve (p = 0.001) abnormalities. No association was found between parotid gland anomaly and ipsilateral internal carotid artery, inner ear, brain, eye, or spine abnormalities (p > 0.6). Salivary gland abnormalities are strikingly common in OAVS. Their detection might help the management of OAVS-associated swallowing and feeding impairment.

  6. 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…

  7. Incidence of abnormal liver biochemical tests in hyperthyroidism.

    PubMed

    Lin, Tiffany Y; Shekar, Anshula O; Li, Ning; Yeh, Michael W; Saab, Sammy; Wilson, Mark; Leung, Angela M

    2017-05-01

    Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen the severity of the abnormal serum liver biochemistries. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis. Single-institution retrospective cohort study. Patients of ≥18 years old receiving medical care at a large, academic, urban US medical centre between 2002-2016. Inclusion criteria were a serum thyroid stimulating hormone (TSH) concentration of <0·3 mIU/l or ICD-9 code for thyrotoxicosis, with thyrotoxicosis confirmed by either a concurrent elevated serum triiodothyronine (T3) or thyroxine (T4) concentration ([total or free] within 3 months), and an available liver biochemical test(s) within 6 months of thyrotoxicosis. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and conjugated bilirubin concentrations. In this cohort of 1514 subjects, the overall incidence of any biochemical liver test abnormality within 6 months of thyrotoxicosis was 39%. An initial serum TSH concentration <0·02 mIU/l, male gender, and African-American race were significant predictors of an abnormal serum liver biochemical test within 6 months of the diagnosis of new-onset untreated thyrotoxicosis. This study identifies risk factors for patients who develop an abnormal serum liver biochemical test result within 6 months of a diagnosis of untreated thyrotoxicosis. © 2017 John Wiley & Sons Ltd.

  8. Intelligent Process Abnormal Patterns Recognition and Diagnosis Based on Fuzzy Logic.

    PubMed

    Hou, Shi-Wang; Feng, Shunxiao; Wang, Hui

    2016-01-01

    Locating the assignable causes by use of the abnormal patterns of control chart is a widely used technology for manufacturing quality control. If there are uncertainties about the occurrence degree of abnormal patterns, the diagnosis process is impossible to be carried out. Considering four common abnormal control chart patterns, this paper proposed a characteristic numbers based recognition method point by point to quantify the occurrence degree of abnormal patterns under uncertain conditions and a fuzzy inference system based on fuzzy logic to calculate the contribution degree of assignable causes with fuzzy abnormal patterns. Application case results show that the proposed approach can give a ranked causes list under fuzzy control chart abnormal patterns and support the abnormity eliminating.

  9. [Normal and abnormal skin color].

    PubMed

    Ortonne, J-P

    2012-11-01

    The varieties of normal skin color in humans range from people of "no color" (pale white) to "people of color" (light brown, dark brown, and black). Skin color is a blend resulting from the skin chromophores red (oxyhaemoglobin), blue (deoxygenated haemoglobin), yellow-orange (carotene, an exogenous pigment), and brown (melanin). Melanin, however, is the major component of skin color ; it is the presence or absence of melanin in the melanosomes in melanocytes and melanin in keratinocytes that is responsible for epidermal pigmentation, and the presence of melanin in macrophages or melanocytes in the dermis that is responsible for dermal pigmentation. Two groups of pigmentary disorders are commonly distinguished: the disorders of the quantitative and qualitative distribution of normal pigment and the abnormal presence of exogenous or endogenous pigments in the skin. The first group includes hyperpigmentations, which clinically manifest by darkening of the skin color, and leukodermia, which is characterized by lightening of the skin. Hypermelanosis corresponds to an overload of melanin or an abnormal distribution of melanin in the skin. Depending on the color, melanodermia (brown/black) and ceruloderma (blue/grey) are distinguished. Melanodermia correspond to epidermal hypermelanocytosis (an increased number of melanocytes) or epidermal hypermelanosis (an increase in the quantity of melanin in the epidermis with no modification of the number of melanocytes). Ceruloderma correspond to dermal hypermelanocytosis (abnormal presence in the dermis of cells synthesizing melanins) ; leakage in the dermis of epidermal melanin also exists, a form of dermal hypermelanosis called pigmentary incontinence. Finally, dyschromia can be related to the abnormal presence in the skin of a pigment of exogenous or endogenous origin. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  10. 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.

  11. Vertical vibration dynamics of acoustically levitated drop containing two immiscible liquids

    NASA Astrophysics Data System (ADS)

    Zang, Duyang; Zhai, Zhicong; Li, Lin; Lin, Kejun; Li, Xiaoguang; Geng, Xingguo

    2016-09-01

    We have studied the levitation and oscillation dynamics of complex drops containing two immiscible liquids. Two types of drops, core-shell drop and abnormal-shaped drop, have been obtained depending on the levitation procedures. The oscillation dynamics of the drops have been studied using a high speed camera. It has been found that the oscillation of the abnormal-shaped drop has a longer oscillation period and decays much faster than that of the core-shell drop, which cannot be accounted for by the air resistance itself. The acoustic streaming induced by ultrasound may bring an additional force against the motion of the drop due to the Bernoulli effect. This is responsible for the enhanced damping during the oscillation in acoustic levitation.

  12. Retinal abnormalities in β-thalassemia major.

    PubMed

    Bhoiwala, Devang L; Dunaief, Joshua L

    2016-01-01

    Patients with beta (β)-thalassemia (β-TM: β-thalassemia major, β-TI: β-thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelial degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-thalassemia major are transfusion dependent and require iron chelation therapy to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by iron chelation therapy. Some who were never treated with iron chelation therapy exhibited retinopathy, and others receiving iron chelation therapy had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-thalassemia major viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Electrocardiographic abnormalities in acute olanzapine poisonings].

    PubMed

    Ciszowski, Krzysztof; Sein Anand, Jacek

    2011-01-01

    Olanzapine is an atypical antipsychotic used for many years in the treatment of schizophrenia and bipolar disorder. Poisonings with this medicine can results with cardiotoxic effects in the form of ECG abnormalities. To evaluate the nature and incidence of electrocardiographic abnormalities in patients with acute olanzapine poisoning. 23 adult (mean age 38.4 +/- 15.5 years) patients with acute olanzapine poisoning, including 10 men (30.4 +/- 8.1 years) and 11 women (45.7 +/- 17.2 years), where 1 man and 1 woman were poisoned twice. The toxic serum level of olanzapine (above 100 ng/mL) was confirmed in each patient. Evaluation of electrocardiograms performed in patients in the first day of hospitalization with automatic measurement of durations of PQ, QRS and QTc and the identification of arrhythmias and conduction disorders on the basis of visual analysis of the ECG waveforms. Statistical analysis of the results using the methods of descriptive statistics. The mean durations of PQ, QRS and QTc in the study group were as follows: 135 +/- 23 ms, 91 +/- 12 ms, and 453 +/- 48 ms, respectively. The most common ECG abnormalities were prolonged QTc and supraventricular tachycardia (including sinus tachycardia) - each 22%; less common were ST-T changes (17%) and supraventricular premature complexes (9%), and only in individual cases (4%) ventricular premature complexes, bundle branch block, sinus bradycardia and atrial fibrillation were present. In the course of acute olanzapine poisonings: (1) prolonged QTc interval is quite common, but rarely leads to torsade de pointes tachycardia; (2) fast supraventricular rhythms are also common, but rarely cause irregular tachyarrhythmias, eg. atrial fibrillation; (3) conduction disorders (atrioventricular blocks, bundle branch blocks) are not typical abnormalities; (4) the observed ECG abnormalities emphasize the need of continuous ECG monitoring in these patients.

  14. Abnormal Grain Growth Suppression in Aluminum Alloys

    NASA Technical Reports Server (NTRS)

    Hales, Stephen J. (Inventor); Claytor, Harold Dale (Inventor); Alexa, Joel A. (Inventor)

    2015-01-01

    The present invention provides a process for suppressing abnormal grain growth in friction stir welded aluminum alloys by inserting an intermediate annealing treatment ("IAT") after the welding step on the article. The IAT may be followed by a solution heat treatment (SHT) on the article under effectively high solution heat treatment conditions. In at least some embodiments, a deformation step is conducted on the article under effective spin-forming deformation conditions or under effective superplastic deformation conditions. The invention further provides a welded article having suppressed abnormal grain growth, prepared by the process above. Preferably the article is characterized with greater than about 90% reduction in area fraction abnormal grain growth in any friction-stir-welded nugget.

  15. Live-cell imaging of nuclear-chromosomal dynamics in bovine in vitro fertilised embryos.

    PubMed

    Yao, Tatsuma; Suzuki, Rie; Furuta, Natsuki; Suzuki, Yuka; Kabe, Kyoko; Tokoro, Mikiko; Sugawara, Atsushi; Yajima, Akira; Nagasawa, Tomohiro; Matoba, Satoko; Yamagata, Kazuo; Sugimura, Satoshi

    2018-05-10

    Nuclear/chromosomal integrity is an important prerequisite for the assessment of embryo quality in artificial reproductive technology. However, lipid-rich dark cytoplasm in bovine embryos prevents its observation by visible light microscopy. We performed live-cell imaging using confocal laser microscopy that allowed long-term imaging of nuclear/chromosomal dynamics in bovine in vitro fertilised (IVF) embryos. We analysed the relationship between nuclear/chromosomal aberrations and in vitro embryonic development and morphological blastocyst quality. Three-dimensional live-cell imaging of 369 embryos injected with mRNA encoding histone H2B-mCherry and enhanced green fluorescent protein (EGFP)-α-tubulin was performed from single-cell to blastocyst stage for eight days; 17.9% reached the blastocyst stage. Abnormalities in the number of pronuclei (PN), chromosomal segregation, cytokinesis, and blastomere number at first cleavage were observed at frequencies of 48.0%, 30.6%, 8.1%, and 22.2%, respectively, and 13.0%, 6.2%, 3.3%, and 13.4%, respectively, for abnormal embryos developed into blastocysts. A multivariate analysis showed that abnormal chromosome segregation (ACS) and multiple PN correlated with delayed timing and abnormal blastomere number at first cleavage, respectively. In morphologically transferrable blastocysts, 30-40% of embryos underwent ACS and had abnormal PN. Live-cell imaging may be useful for analysing the association between nuclear/chromosomal dynamics and embryonic development in bovine embryos.

  16. Gastric emptying abnormal in duodenal ulcer

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

    Holt, S.; Heading, R.C.; Taylor, T.V.

    1986-07-01

    To investigate the possibility that an abnormality of gastric emptying exists in duodenal ulcer and to determine if such an abnormality persists after ulcer healing, scintigraphic gastric emptying measurements were undertaken in 16 duodenal ulcer patients before, during, and after therapy with cimetidine; in 12 patients with pernicious anemia, and in 12 control subjects. No difference was detected in the rate or pattern of gastric emptying in duodenal ulcer patients before and after ulcer healing with cimetidine compared with controls, but emptying of the solid component of the test meal was more rapid during treatment with the drug. Comparison ofmore » emptying patterns obtained in duodenal ulcer subjects during and after cimetidine treatment with those obtained in pernicious anemia patients and controls revealed a similar relationship that was characterized by a tendency for reduction in the normal differentiation between the emptying of solid and liquid from the stomach. The similarity in emptying patterns in these groups of subjects suggests that gastric emptying of solids may be influenced by changes in the volume of gastric secretion. The failure to detect an abnormality of gastric emptying in duodenal ulcer subjects before and after ulcer healing calls into question the widespread belief that abnormally rapid gastric emptying is a feature with pathogenetic significance in duodenal ulcer disease.« less

  17. Risk of specific congenital abnormalities in offspring of women with diabetes.

    PubMed

    Nielsen, G L; Nørgard, B; Puho, E; Rothman, K J; Sørensen, H T; Czeizel, A E

    2005-06-01

    To assess the extent to which the increased risk of congenital abnormalities seen in women with pre-gestational insulin-treated diabetes mellitus is unspecific or related to the embryology of specific organs. Cases with congenital abnormalities were identified in the population-based Hungarian Congenital Abnormality Registry from 1980 to 1996 with two newborn children without congenital abnormality selected from the National Birth Registry as controls. We adjusted for parity, maternal age, and use of antipsychotic drugs. Among cases we found 63/22,843 babies with maternal diabetes compared with 50/38,151 in the control group [adjusted prevalence odds ratio (POR) 2.1; 95% CI 1.5-3.1]. The association was strongest for the following congenital abnormalities: renal agenesis (POR: 14.8; 95% CI, 3.5-62.1), obstructive congenital abnormalities of the urinary tract (POR: 4.3; 95% CI, 1.3-13.9), cardiovascular congenital abnormalities (POR: 3.4; 95% CI, 2.0-5.7), and multiple congenital abnormalities (POR: 5.0; 95% CI, 2.4-10.2). These data indicate that pre-gestational maternal diabetes is associated with strong teratogenic effects on the kidney, urinary tract, and heart, and strongly associated with multiple congenital abnormalities. We found no material association between diabetes and spinal congenital abnormalities and limb deficiencies.

  18. Chromosome and molecular abnormalities in myelodysplastic syndromes.

    PubMed

    Fenaux, Pierre

    2001-06-01

    Cytogenetic abnormalities are seen in approximately 50% of cases of myelodysplastic syndrome (MDS) and 80% of cases of secondary MDS (following chemotherapy or radiotherapy). These abnormalities generally consist of partial or complete chromosome deletion or addition (del5q, -7, +8, -Y, del20q), whereas balanced or unbalanced translocations are rarely found in MDS. Fluorescence hybridization techniques (fluorescence in situ hybridization [FISH], multiplex FISH, and spectral karyotyping) are useful in detecting chromosomal anomalies in cases in which few mitoses are obtained or rearrangements are complex. Ras mutations are the molecular abnormalities most frequently found in MDS, followed by p15 gene hypermethylation, FLT3 duplications, and p53 mutations, but none of these abnormalities are specific for MDS. The rare cases of balanced translocations in MDS have allowed the identification of genes whose rearrangements appear to play a role in the pathogenesis of some cases of MDS. These genes include MDS1-EVI1 in t(3;3) or t(3;21) translocations, TEL in t(5;12), HIP1 in t(5;7), MLF1 in t(3;5), and MEL1 in t(1;3). Genes more frequently implicated in the pathogenesis of MDS cases, such as those involving del5q, remain unknown, although some candidate genes are currently being studied. Cytogenetic and known molecular abnormalities generally carry a poor prognosis in MDS and can be incorporated into prognostic scoring systems such as the International Prognostic Scoring System.

  19. Mechanisms and consequences of paternally transmitted chromosomal abnormalities

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

    Marchetti, F; Wyrobek, A J

    Paternally transmitted chromosomal damage has been associated with pregnancy loss, developmental and morphological defects, infant mortality, infertility, and genetic diseases in the offspring including cancer. There is epidemiological evidence linking paternal exposure to occupational or environmental agents with an increased risk of abnormal reproductive outcomes. There is also a large body of literature on germ cell mutagenesis in rodents showing that treatment of male germ cells with mutagens has dramatic consequences on reproduction producing effects such as those observed in human epidemiological studies. However, we know very little about the etiology, transmission and early embryonic consequences of paternally-derived chromosomal abnormalities.more » The available evidence suggests that: (1) there are distinct patterns of germ cell-stage differences in the sensitivity of induction of transmissible genetic damage with male postmeiotic cells being the most sensitive; (2) cytogenetic abnormalities at first metaphase after fertilization are critical intermediates between paternal exposure and abnormal reproductive outcomes; and, (3) there are maternally susceptibility factors that may have profound effects on the amount of sperm DNA damage that is converted into chromosomal aberrations in the zygote and directly affect the risk for abnormal reproductive outcomes.« less

  20. Abnormal Uterine Bleeding: American College of Nurse-Midwives.

    PubMed

    2016-07-01

    Variations in uterine bleeding, termed abnormal uterine bleeding, occur commonly among women and often are physiologic in nature with no significant consequences. However, abnormal uterine bleeding can cause significant distress to women or may signify an underlying pathologic condition. Most women experience variations in menstrual and perimenstrual bleeding in their lifetimes; therefore, the ability of the midwife to differentiate between normal and abnormal bleeding is a key diagnostic skill. A comprehensive history and use of the PALM-COEIN classification system will provide clear guidelines for clinical management, evidence-based treatment, and an individualized plan of care. The purpose of this Clinical Bulletin is to define and describe classifications of abnormal uterine bleeding, review updated terminology, and identify methods of assessment and treatment using a woman-centered approach. © 2016 by the American College of Nurse-Midwives.

  1. Propofol and Sevoflurane Differentially Modulate Cortical Depolarization following Electric Stimulation of the Ventrobasal Thalamus.

    PubMed

    Kratzer, Stephan; Mattusch, Corinna; Garcia, Paul S; Schmid, Sebastian; Kochs, Eberhard; Rammes, Gerhard; Schneider, Gerhard; Kreuzer, Matthias; Haseneder, Rainer

    2017-01-01

    The neuronal mechanisms how anesthetics lead to loss of consciousness are unclear. Thalamocortical interactions are crucially involved in conscious perception; hence the thalamocortical network might be a promising target for anesthetic modulation of neuronal information pertaining to arousal and waking behavior. General anesthetics affect the neurophysiology of the thalamus and the cortex but the exact mechanisms of how anesthetics interfere with processing thalamocortical information remain to be elucidated. Here we investigated the effect of the anesthetic agents sevoflurane and propofol on thalamocortical network activity in vitro . We used voltage-sensitive dye imaging techniques to analyze the cortical depolarization in response to stimulation of the thalamic ventrobasal nucleus in brain slices from mice. Exposure to sevoflurane globally decreased cortical depolarization in a dose-dependent manner. Sevoflurane reduced the intensity and extent of cortical depolarization and delayed thalamocortical signal propagation. In contrast, propofol neither affected area nor amplitude of cortical depolarization. However, propofol exposure resulted in regional changes in spatial distribution of maximum fluorescence intensity in deep regions of the cortex. In summary, our experiments revealed substance-specific effects on the thalamocortical network. Functional changes of the neuronal network are known to be pivotally involved in the anesthetic-induced loss of consciousness. Our findings provide further evidence that the mechanisms of anesthetic-mediated loss of consciousness are drug- and pathway-specific.

  2. The nurse response to abnormal vital sign recording in the emergency department.

    PubMed

    Johnson, Kimberly D; Mueller, Lindsey; Winkelman, Chris

    2017-01-01

    To examine what occurs after a recorded observation of at least one abnormal vital sign in the emergency department. The aims were to determine how often abnormal vital signs were recorded, what interventions were documented, and what factors were associated with documented follow-up for abnormal vital signs. Monitoring quality of care, and preventing or intervening before harm occurs to patients are central to nurses' roles. Abnormal vital signs have been associated with poor patient outcomes and require follow-up after the observation of abnormal readings to prevent patient harm related to a deteriorating status. This documentation is important to quality and safety of care. Observational, retrospective chart review. Modified Early Warning Score was calculated for all recorded vital signs for 195 charts. Comparisons were made between groups: (1) no abnormal vital signs, (2) abnormal vital sign present, but normal Modified Early Warning Score and (3) critically abnormal Modified Early Warning Score. About 62·1% of charts had an abnormal vital sign documented. Critically abnormal values were present in 14·9%. No documentation was present in 44·6% of abnormal cases. When interventions were documented, it was usually to notify the physician. The timing within the emergency department visit when the abnormalities were observed and the degree of abnormality had significant relationships to the presence of documentation. It is doubtful that nurses do not recognise abnormalities because more severely abnormal vital signs were more likely to have documented follow-up. Perhaps the interruptive nature of the emergency department or the prioritised actions of the nurse impacted documentation within this study. Further research is required to determine why follow-up is not being documented. To ensure safety and quality of patient care, accurate documentation of responses to abnormal vital signs is required. © 2016 John Wiley & Sons Ltd.

  3. Lung volumes and emphysema in smokers with interstitial lung abnormalities.

    PubMed

    Washko, George R; Hunninghake, Gary M; Fernandez, Isis E; Nishino, Mizuki; Okajima, Yuka; Yamashiro, Tsuneo; Ross, James C; Estépar, Raúl San José; Lynch, David A; Brehm, John M; Andriole, Katherine P; Diaz, Alejandro A; Khorasani, Ramin; D'Aco, Katherine; Sciurba, Frank C; Silverman, Edwin K; Hatabu, Hiroto; Rosas, Ivan O

    2011-03-10

    Cigarette smoking is associated with emphysema and radiographic interstitial lung abnormalities. The degree to which interstitial lung abnormalities are associated with reduced total lung capacity and the extent of emphysema is not known. We looked for interstitial lung abnormalities in 2416 (96%) of 2508 high-resolution computed tomographic (HRCT) scans of the lung obtained from a cohort of smokers. We used linear and logistic regression to evaluate the associations between interstitial lung abnormalities and HRCT measurements of total lung capacity and emphysema. Interstitial lung abnormalities were present in 194 (8%) of the 2416 HRCT scans evaluated. In statistical models adjusting for relevant covariates, interstitial lung abnormalities were associated with reduced total lung capacity (-0.444 liters; 95% confidence interval [CI], -0.596 to -0.292; P<0.001) and a lower percentage of emphysema defined by lung-attenuation thresholds of -950 Hounsfield units (-3%; 95% CI, -4 to -2; P<0.001) and -910 Hounsfield units (-10%; 95% CI, -12 to -8; P<0.001). As compared with participants without interstitial lung abnormalities, those with abnormalities were more likely to have a restrictive lung deficit (total lung capacity <80% of the predicted value; odds ratio, 2.3; 95% CI, 1.4 to 3.7; P<0.001) and were less likely to meet the diagnostic criteria for chronic obstructive pulmonary disease (COPD) (odds ratio, 0.53; 95% CI, 0.37 to 0.76; P<0.001). The effect of interstitial lung abnormalities on total lung capacity and emphysema was dependent on COPD status (P<0.02 for the interactions). Interstitial lung abnormalities were positively associated with both greater exposure to tobacco smoke and current smoking. In smokers, interstitial lung abnormalities--which were present on about 1 of every 12 HRCT scans--were associated with reduced total lung capacity and a lesser amount of emphysema. (Funded by the National Institutes of Health and the Parker B. Francis Foundation

  4. Abnormal Head Position in Infantile Nystagmus Syndrome

    PubMed Central

    Noval, Susana; González-Manrique, Mar; Rodríguez-Del Valle, José María; Rodríguez-Sánchez, José María

    2011-01-01

    Infantile nystagmus is an involuntary, bilateral, conjugate, and rhythmic oscillation of the eyes which is present at birth or develops within the first 6 months of life. It may be pendular or jerk-like and, its intensity usually increases in lateral gaze, decreasing with convergence. Up to 64% of all patients with nystagmus also present strabismus, and even more patients have an abnormal head position. The abnormal head positions are more often horizontal, but they may also be vertical or take the form of a tilt, even though the nystagmus itself is horizontal. The aim of this article is to review available information about the origin and treatment of the abnormal head position associated to nystagmus, and to describe our treatment strategies. PMID:24533187

  5. Advances in understanding paternally transmitted Chromosomal Abnormalities

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

    Marchetti, F; Sloter, E; Wyrobek, A J

    2001-03-01

    Multicolor FISH has been adapted for detecting the major types of chromosomal abnormalities in human sperm including aneuploidies for clinically-relevant chromosomes, chromosomal aberrations including breaks and rearrangements, and other numerical abnormalities. The various sperm FISH assays have been used to evaluate healthy men, men of advanced age, and men who have received mutagenic cancer therapy. The mouse has also been used as a model to investigate the mechanism of paternally transmitted genetic damage. Sperm FISH for the mouse has been used to detect chromosomally abnormal mouse sperm, while the PAINT/DAPI analysis of mouse zygotes has been used to evaluate themore » types of chromosomal defects that can be paternally transmitted to the embryo and their effects on embryonic development.« less

  6. Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir; Manzanares, José A.; Mafe, Salvador

    2017-04-01

    We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ . This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

  7. Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states.

    PubMed

    García-Morales, Vladimir; Manzanares, José A; Mafe, Salvador

    2017-04-01

    We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ. This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

  8. The pattern of thalamocortical and brain stem projections to the vibrissae-related sensory and motor cortices in de-whiskered congenital hypothyroid rats.

    PubMed

    Afarinesh, Mohammad Reza; Behzadi, Gila

    2017-08-01

    The present study is designed to investigate the plastic organization of the thalamo-cortical (TC) and brain stem afferents of whisker primary sensory (wS1) and motor (wM1) cortical areas in congenital hypothyroid (CH) pups following whisker deprivation (WD) from neonatal to adolescence period. Maternal hypothyroidism was induced by adding propylthiouracil (PTU) to the drinking water from early embryonic day 16 to postnatal day (PND) 60. Pregnant rats were divided into intact and CH groups (n = 8). In each group, the total whiskers of pups (4 of 8) were trimmed continuously from PND 1 to PND 60. Retrograde tracing technique with WGA-HRP was performed in the present study. Retrogradely labeled neurons were observed in the specific thalamic nuclei (VPM and VL) following separately WGA-HRP injections into wS1/M1 cortical areas. The number of labeled cells in the VPM, VL, VM and PO nuclei of the thalamus significantly decreased in CH offsprings rats (P < 0.05). Neonatal WD did not show any significant effects on the number of VPM, VL, VM and PO labeled projection neurons to wS1 and wM1 cortical areas. In addition, retrogradely labeled neurons in dorsal raphe (DR) and locus coeruleus (LC) nuclei were observed in all experimental groups. The number of DR and LC labeled neurons were higher in the CH and whisker deprived groups compared to their matching controls (P < 0.05). Upon our results, CH and WD had no synergic or additive effects on the TC and brain stem afferent patterns of barrel sensory and motor cortices.

  9. Nightmare and Abnormal Dreams: Rare Side Effects of Metformin?

    PubMed Central

    Yanto, Theo Audi; Kosasih, Felicia Nathania

    2018-01-01

    Background Metformin is widely known as an antidiabetic agent which has significant gastrointestinal side effects, but nightmares and abnormal dreams as its adverse reactions are not well reported. Case Presentation Herein we present a case of 56-year-old male patient with no known history of recurrent nightmares and sleep disorder, experiencing nightmare and abnormal dreams directly after consumption of 750 mg extended release metformin. He reported his dream as an unpleasant experience which awakened him at night with negative feelings. The nightmare only lasted for a night, but his dreams every night thereafter seemed abnormal. The dreams were vivid and indescribable. The disappearance and occurrence of abnormal dreams ensued soon after the drug was discontinued and rechallenged. The case was assessed using Naranjo Adverse Drug Reaction (ADR) probability scale and resulted as probable causality. Conclusion Metformin might be the underlying cause of nightmare and abnormal dreams in this patient. More studies are needed to confirm the association and causality of this findings. PMID:29581904

  10. Imaginal Disc Abnormalities in Lethal Mutants of Drosophila

    PubMed Central

    Shearn, Allen; Rice, Thomas; Garen, Alan; Gehring, Walter

    1971-01-01

    Late lethal mutants of Drosophila melanogaster, dying after the larval stage of development, were isolated. The homozygous mutant larvae were examined for abnormal imaginal disc morphology, and the discs were injected into normal larval hosts to test their capacities to differentiate into adult structures. In about half of the mutants analyzed, disc abnormalities were found. Included among the abnormalities were missing discs, small discs incapable of differentiating, morphologically normal discs with limited capacities for differentiation, and discs with homeotic transformations. In some mutants all discs were affected, and in others only certain discs. The most extreme abnormal phenotype is a class of “discless” mutants. The viability of these mutant larvae indicates that the discs are essential only for the development of an adult and not of a larva. The late lethals are therefore a major source of mutants for studying the genetic control of disc formation. Images PMID:5002822

  11. Abnormally high formation pressures, Potwar Plateau, Pakistan

    USGS Publications Warehouse

    Law, B.E.; Shah, S.H.A.; Malik, M.A.

    1998-01-01

    Abnormally high formation pressures in the Potwar Plateau of north-central Pakistan are major obstacles to oil and gas exploration. Severe drilling problems associated with high pressures have, in some cases, prevented adequate evaluation of reservoirs and significantly increased drilling costs. Previous investigations of abnormal pressure in the Potwar Plateau have only identified abnormal pressures in Neogene rocks. We have identified two distinct pressure regimes in this Himalayan foreland fold and thrust belt basin: one in Neogene rocks and another in pre-Neogene rocks. Pore pressures in Neogene rocks are as high as lithostatic and are interpreted to be due to tectonic compression and compaction disequilibrium associated with high rates of sedimentation. Pore pressure gradients in pre-Neogene rocks are generally less than those in Neogene rocks, commonly ranging from 0.5 to 0.7 psi/ft (11.3 to 15.8 kPa/m) and are most likely due to a combination of tectonic compression and hydrocarbon generation. The top of abnormally high pressure is highly variable and doesn't appear to be related to any specific lithologic seal. Consequently, attempts to predict the depth to the top of overpressure prior to drilling are precluded.

  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. Abnormal interhemispheric connectivity in male psychopathic offenders.

    PubMed

    Hoppenbrouwers, Sylco S; De Jesus, Danilo R; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J; Schutter, Dennis J L G

    2014-01-01

    Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders.

  14. The psychosocial impact of an abnormal cervical smear result.

    PubMed

    Drolet, Mélanie; Brisson, Marc; Maunsell, Elizabeth; Franco, Eduardo L; Coutlée, François; Ferenczy, Alex; Fisher, William; Mansi, James A

    2012-10-01

    Data on the impact of abnormal cervical smear results on health-related quality of life (HrQoL) are scarce. We aimed to (i) prospectively assess the HrQoL of women who were informed of an abnormal smear result; (ii) identify predictors of greater negative psychosocial impact of an abnormal result; and (iii) prospectively estimate the quality-adjusted life-years (QALYs) lost following an abnormal result. Between 08/2006 and 08/2008, 492 women with an abnormal result and 460 women with a normal result, frequency matched for age and clinic, were recruited across Canada. HrQoL was measured at recruitment and 4 and 12 weeks later with the EuroQol, Short Form-12, short Spielberg State-Trait Anxiety Inventory (STAI) and HPV Impact Profile. Three blocks of potential predictors of higher psychosocial impact were tested by hierarchical modeling: (i) socio-demographics; (ii) sexual activity; and (iii) smear result severity, communication, and understanding. Receiving an abnormal result significantly increased anxiety (STAI mean difference between both groups = 8.3). Initial anxiety decreased over time for the majority of women. However, 35% of women had clinically meaningful anxiety at 12 weeks (i.e. STAI scores ≥0.5 standard deviation of the controls). These women reported a lower socio-economic level, did not completely understand the information about their result and perceived themselves at higher risk of cancer. QALY lost following an abnormal result were between 0.007 and 0.009. Receiving an abnormal smear has a statistically significant and clinically meaningful negative impact on mental health. However, this negative impact subsides after 12 weeks for the majority of women. Copyright © 2011 John Wiley & Sons, Ltd.

  15. 42 CFR 37.54 - Notification of abnormal radiographic findings.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... shape or size, tuberculosis, lung cancer, or any other significant abnormal findings other than..., tuberculosis, cancer, complicated pneumoconiosis, and any other significant abnormal findings, NIOSH will...

  16. Eye movement abnormalities in essential tremor

    PubMed Central

    Plinta, Klaudia; Krzak-Kubica, Agnieszka; Zajdel, Katarzyna; Falkiewicz, Marcel; Dylak, Jacek; Ober, Jan; Szczudlik, Andrzej; Rudzińska, Monika

    2016-01-01

    Abstract Essential tremor (ET) is the most prevalent movement disorder, characterized mainly by an action tremor of the arms. Only a few studies published as yet have assessed oculomotor abnormalities in ET and their results are unequivocal. The aim of this study was to assess the oculomotor abnormalities in ET patients compared with the control group and to find the relationship between oculomotor abnormalities and clinical features of ET patients. We studied 50 ET patients and 42 matched by age and gender healthy controls. Saccadometer Advanced (Ober Consulting, Poland) was used to investigate reflexive, pace-induced and cued saccades and conventional electrooculography for evaluation of smooth pursuit and fixation. The severity of the tremor was assessed by the Clinical Rating Scale for Tremor. Significant differences between ET patients and controls were found for the incidence of reflexive saccades dysmetria and deficit of smooth pursuit. Reflexive saccades dysmetria was more frequent in patients in the second and third phase of ET compared to the first phase. The reflexive saccades latency increase was correlated with severity of the tremor. In conclusion, oculomotor abnormalities were significantly more common in ET patients than in healthy subjects. The most common oculomotor disturbances in ET were reflexive saccades dysmetria and slowing of smooth pursuit. The frequency of reflexive saccades dysmetria increased with progression of ET. The reflexive saccades latency increase was related to the severity of tremor. PMID:28149393

  17. Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Paulk, H. H.; And Others

    1977-01-01

    Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

  18. Detection of dominant flow and abnormal events in surveillance video

    NASA Astrophysics Data System (ADS)

    Kwak, Sooyeong; Byun, Hyeran

    2011-02-01

    We propose an algorithm for abnormal event detection in surveillance video. The proposed algorithm is based on a semi-unsupervised learning method, a kind of feature-based approach so that it does not detect the moving object individually. The proposed algorithm identifies dominant flow without individual object tracking using a latent Dirichlet allocation model in crowded environments. It can also automatically detect and localize an abnormally moving object in real-life video. The performance tests are taken with several real-life databases, and their results show that the proposed algorithm can efficiently detect abnormally moving objects in real time. The proposed algorithm can be applied to any situation in which abnormal directions or abnormal speeds are detected regardless of direction.

  19. Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions.

    PubMed

    Price, C J; Warburton, E A; Moore, C J; Frackowiak, R S; Friston, K J

    2001-05-15

    Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.

  20. Abnormal grain growth in AISI 304L stainless steel

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

    Shirdel, M., E-mail: mshirdel1989@ut.ac.ir; Mirzadeh, H., E-mail: hmirzadeh@ut.ac.ir; Advanced Metalforming and Thermomechanical Processing Laboratory, School of Metallurgy and Materials Engineering, University of Tehran, Tehran

    2014-11-15

    The microstructural evolution during abnormal grain growth (secondary recrystallization) in 304L stainless steel was studied in a wide range of annealing temperatures and times. At relatively low temperatures, the grain growth mode was identified as normal. However, at homologous temperatures between 0.65 (850 °C) and 0.7 (900 °C), the observed transition in grain growth mode from normal to abnormal, which was also evident from the bimodality in grain size distribution histograms, was detected to be caused by the dissolution/coarsening of carbides. The microstructural features such as dispersed carbides were characterized by optical metallography, X-ray diffraction, scanning electron microscopy, energy dispersivemore » X-ray analysis, and microhardness. Continued annealing to a long time led to the completion of secondary recrystallization and the subsequent reappearance of normal growth mode. Another instance of abnormal grain growth was observed at homologous temperatures higher than 0.8, which may be attributed to the grain boundary faceting/defaceting phenomenon. It was also found that when the size of abnormal grains reached a critical value, their size will not change too much and the grain growth behavior becomes practically stagnant. - Highlights: • Abnormal grain growth (secondary recrystallization) in AISI 304L stainless steel • Exaggerated grain growth due to dissolution/coarsening of carbides • The enrichment of carbide particles by titanium • Abnormal grain growth due to grain boundary faceting at very high temperatures • The stagnancy of abnormal grain growth by annealing beyond a critical time.« less

  1. Musculo-Skeletal Abnormalities in Patients with Marfan Syndrome

    PubMed Central

    Al Kaissi, Ali; Zwettler, Elisabeth; Ganger, Rudolf; Schreiner, Simone; Klaushofer, Klaus; Grill, Franz

    2013-01-01

    Background A leptosomic body type is tall and thin with long hands. Marfanoid features may be familial in nature or pathological, as occurs in congenital contractual arachnodactyly (Beal’s syndrome) and Shprintzen-Goldberg syndrome mimicking some of the changes of Marfan syndrome, although not accompanied by luxation of lens and dissecting aneurysm of aorta. Methods In this article we collected eight patients who were consistent with the diagnosis of Marfan syndrome via phenotypic and genotypic characterization. Results Our patients manifested a constellation of variable presentations of musculo-skeletal abnormalities ranging from developmental dysplasia of the hip, protrusio acetabuli, leg length inequality, patellar instability, scoliosis, to early onset osteoarthritis. Each abnormality has been treated accordingly. Conclusion This is the first paper which includes the diagnosis and the management of the associated musculo-skeletal abnormalities in patients with Marfan syndrome, stressing that patients with Marfan syndrome are exhibiting great variability in the natural history and the severity of musculo-skeletal abnormalities. PMID:23399831

  2. Abnormal Spatial Asymmetry of Selective Attention in ADHD

    ERIC Educational Resources Information Center

    Chan, Edgar; Mattingley, Jason B.; Huang-Pollock, Cynthia; English, Therese; Hester, Robert; Vance, Alasdair; Bellgrove, Mark A.

    2009-01-01

    Background: Evidence for a selective attention abnormality in children with attention deficit hyperactivity disorder (ADHD) has been hard to identify using conventional methods from cognitive science. This study tested whether the presence of selective attention abnormalities in ADHD may vary as a function of perceptual load and target…

  3. Who should be screened for chromosomal abnormalities before ICSI treatment?

    PubMed

    Dul, E C; van Ravenswaaij-Arts, C M A; Groen, H; van Echten-Arends, J; Land, J A

    2010-11-01

    Guidelines on karyotyping infertile men before ICSI treatment are not consistent. Most guidelines recommend chromosomal screening in azoospermic and severe oligozoospermic men, because they are assumed to have the highest risk of abnormalities. We performed a retrospective cohort study in azoospermic men and men eligible for ICSI. We determined the prevalence of chromosomal abnormalities in relation to sperm concentration and compared our data to studies in the literature. A high prevalence of chromosomal abnormalities in azoospermic men was found, but no difference in the prevalence of abnormalities was seen between different sperm concentration categories in non-azoospermic men. This raises the question of who should be screened for chromosomal abnormalities before ICSI treatment. Considering the costs and benefits, we would propose limiting screening to infertile couples with non-obstructive azoospermia.

  4. Abnormal regional cerebral blood flow in childhood autism.

    PubMed

    Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

    2000-09-01

    Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

  5. Incidence of Abnormal Liver Biochemical Tests in Hyperthyroidism

    PubMed Central

    Lin, Tiffany Y.; Shekar, Anshula O.; Li, Ning; Yeh, Michael W.; Saab, Sammy; Wilson, Mark; Leung, Angela M.

    2017-01-01

    Objective Abnormal serum liver function tests are common in patients with untreated thyrotoxicosis, even prior to the initiation of antithyroidal medications that may worsen their severity. There is a wide range of the incidence of these abnormalities in the published literature. The aim of this study was to assess the risks factors and threshold of thyrotoxicosis severity for developing an abnormal liver biochemical test upon the diagnosis of new thyrotoxicosis. Design Single-institution retrospective cohort study. Patients Patients ≥18 years old receiving medical care at a large, academic, urban U.S. medical center between 2002–2016. Measurements Inclusion criteria were a serum thyroid stimulating hormone [TSH] concentration < 0.3 mIU/L or ICD-9 code for thyrotoxicosis, with thyrotoxicosis confirmed by either a concurrent elevated serum triiodothyronine (T3) and/or thyroxine (T4) concentration [total or free] within 3 months), and an available liver biochemical test(s) within 6 months of thyrotoxicosis. The biochemical liver tests assessed were serum aspartate transaminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma-glutamyltransferase (GGT), total bilirubin, and conjugated bilirubin concentrations. Results In this cohort of 1,514 subjects, the overall incidence of any biochemical liver test abnormality within 6 months of thyrotoxicosis was 39%. An initial serum TSH concentration <0.02 mIU/L, male gender, and African-American race were significant predictors of an abnormal serum liver biochemical test within 6 months of the diagnosis of new-onset untreated thyrotoxicosis. Conclusions This study identifies risk factors for patients who develop an abnormal serum liver biochemical test result within 6 months of a diagnosis of untreated thyrotoxicosis. PMID:28199740

  6. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling

    PubMed Central

    Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

    2014-01-01

    Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. PMID:25224226

  7. MACF1 regulates the migration of pyramidal neurons via microtubule dynamics and GSK-3 signaling.

    PubMed

    Ka, Minhan; Jung, Eui-Man; Mueller, Ulrich; Kim, Woo-Yang

    2014-11-01

    Neuronal migration and subsequent differentiation play critical roles for establishing functional neural circuitry in the developing brain. However, the molecular mechanisms that regulate these processes are poorly understood. Here, we show that microtubule actin crosslinking factor 1 (MACF1) determines neuronal positioning by regulating microtubule dynamics and mediating GSK-3 signaling during brain development. First, using MACF1 floxed allele mice and in utero gene manipulation, we find that MACF1 deletion suppresses migration of cortical pyramidal neurons and results in aberrant neuronal positioning in the developing brain. The cell autonomous deficit in migration is associated with abnormal dynamics of leading processes and centrosomes. Furthermore, microtubule stability is severely damaged in neurons lacking MACF1, resulting in abnormal microtubule dynamics. Finally, MACF1 interacts with and mediates GSK-3 signaling in developing neurons. Our findings establish a cellular mechanism underlying neuronal migration and provide insights into the regulation of cytoskeleton dynamics in developing neurons. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. How Abnormal Is the Behaviour of Captive, Zoo-Living Chimpanzees?

    PubMed Central

    Birkett, Lucy P.; Newton-Fisher, Nicholas E.

    2011-01-01

    Background Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. Methods We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Results, Conclusion and Significance Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is ‘normal’ in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare

  9. How abnormal is the behaviour of captive, zoo-living chimpanzees?

    PubMed

    Birkett, Lucy P; Newton-Fisher, Nicholas E

    2011-01-01

    Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is 'normal' in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications.

  10. Resting-state Abnormalities in Heroin-dependent Individuals.

    PubMed

    Pandria, Niki; Kovatsi, Leda; Vivas, Ana B; Bamidis, Panagiotis D

    2018-05-15

    Drug addiction is a major health problem worldwide. Recent neuroimaging studies have shed light into the underlying mechanisms of drug addiction as well as its consequences to the human brain. The most vulnerable, to heroin addiction, brain regions have been reported to be specific prefrontal, parietal, occipital, and temporal regions, as well as, some subcortical regions. The brain regions involved are usually linked with reward, motivation/drive, memory/learning, inhibition as well as emotional control and seem to form circuits that interact with each other. So, along with neuroimaging studies, recent advances in resting-state dynamics might allow further assessments upon the multilayer complexity of addiction. In the current manuscript, we comprehensively review and discuss existing resting-state neuroimaging findings classified into three overlapping and interconnected groups: functional connectivity alterations, structural deficits and abnormal topological properties. Moreover, behavioral traits of heroin-addicted individuals as well as the limitations of the currently available studies are also reviewed. Finally, in need of a contemporary therapy a multimodal therapeutic approach is suggested using classical treatment practices along with current neurotechonologies, such as neurofeedback and goal-oriented video-games. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  11. Simulated combined abnormal environment fire calculations for aviation impacts.

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

    Brown, Alexander L.

    2010-08-01

    Aircraft impacts at flight speeds are relevant environments for aircraft safety studies. This type of environment pertains to normal environments such as wildlife impacts and rough landings, but also the abnormal environment that has more recently been evidenced in cases such as the Pentagon and World Trade Center events of September 11, 2001, and the FBI building impact in Austin. For more severe impacts, the environment is combined because it involves not just the structural mechanics, but also the release of the fuel and the subsequent fire. Impacts normally last on the order of milliseconds to seconds, whereas the firemore » dynamics may last for minutes to hours, or longer. This presents a serious challenge for physical models that employ discrete time stepping to model the dynamics with accuracy. Another challenge is that the capabilities to model the fire and structural impact are seldom found in a common simulation tool. Sandia National Labs maintains two codes under a common architecture that have been used to model the dynamics of aircraft impact and fire scenarios. Only recently have these codes been coupled directly to provide a fire prediction that is better informed on the basis of a detailed structural calculation. To enable this technology, several facilitating models are necessary, as is a methodology for determining and executing the transfer of information from the structural code to the fire code. A methodology has been developed and implemented. Previous test programs at the Sandia National Labs sled track provide unique data for the dynamic response of an aluminum tank of liquid water impacting a barricade at flight speeds. These data are used to validate the modeling effort, and suggest reasonable accuracy for the dispersion of a non-combustible fluid in an impact environment. The capability is also demonstrated with a notional impact of a fuel-filled container at flight speed. Both of these scenarios are used to evaluate numeric

  12. Abnormal interhemispheric connectivity in male psychopathic offenders

    PubMed Central

    Hoppenbrouwers, Sylco S.; De Jesus, Danilo R.; Sun, Yinming; Stirpe, Tania; Hofman, Dennis; McMaster, Jeff; Hughes, Ginny; Daskalakis, Zafiris J.; Schutter, Dennis J.L.G.

    2014-01-01

    Background Psychopathic offenders inevitably violate interpersonal norms and frequently resort to aggressive and criminal behaviour. The affective and cognitive deficits underlying these behaviours have been linked to abnormalities in functional interhemispheric connectivity. However, direct neurophysiological evidence for dysfunctional connectivity in psychopathic offenders is lacking. Methods We used transcranial magnetic stimulation combined with electroencephalography to examine interhemispheric connectivity in the dorsolateral and motor cortex in a sample of psychopathic offenders and healthy controls. We also measured intracortical inhibition and facilitation over the left and right motor cortex to investigate the effects of local cortical processes on interhemispheric connectivity. Results We enrolled 17 psychopathic offenders and 14 controls in our study. Global abnormalities in right to left functional connectivity were observed in psychopathic offenders compared with controls. Furthermore, in contrast to controls, psychopathic offenders showed increased intracortical inhibition in the right, but not the left, hemisphere. Limitations The relatively small sample size limited the sensitivity to show that the abnormalities in interhemispheric connectivity were specifically related to the dorsolateral prefrontal cortex in psychopathic offenders. Conclusion To our knowledge, this study provides the first neurophysiological evidence for abnormal interhemispheric connectivity in psychopathic offenders and may further our understanding of the disruptive antisocial behaviour of these offenders. PMID:23937798

  13. Brain abnormality segmentation based on l1-norm minimization

    NASA Astrophysics Data System (ADS)

    Zeng, Ke; Erus, Guray; Tanwar, Manoj; Davatzikos, Christos

    2014-03-01

    We present a method that uses sparse representations to model the inter-individual variability of healthy anatomy from a limited number of normal medical images. Abnormalities in MR images are then defined as deviations from the normal variation. More precisely, we model an abnormal (pathological) signal y as the superposition of a normal part ~y that can be sparsely represented under an example-based dictionary, and an abnormal part r. Motivated by a dense error correction scheme recently proposed for sparse signal recovery, we use l1- norm minimization to separate ~y and r. We extend the existing framework, which was mainly used on robust face recognition in a discriminative setting, to address challenges of brain image analysis, particularly the high dimensionality and low sample size problem. The dictionary is constructed from local image patches extracted from training images aligned using smooth transformations, together with minor perturbations of those patches. A multi-scale sliding-window scheme is applied to capture anatomical variations ranging from fine and localized to coarser and more global. The statistical significance of the abnormality term r is obtained by comparison to its empirical distribution through cross-validation, and is used to assign an abnormality score to each voxel. In our validation experiments the method is applied for segmenting abnormalities on 2-D slices of FLAIR images, and we obtain segmentation results consistent with the expert-defined masks.

  14. Factors associated with abnormal eating attitudes among Greek adolescents.

    PubMed

    Bilali, Aggeliki; Galanis, Petros; Velonakis, Emmanuel; Katostaras, Theofanis

    2010-01-01

    To estimate the prevalence of abnormal eating attitudes among Greek adolescents and identify possible risk factors associated with these attitudes. Cross-sectional, school-based study. Six randomly selected schools in Patras, southern Greece. The study population consisted of 540 Greek students aged 13-18 years, and the response rate was 97%. The dependent variable was scores on the Eating Attitudes Test-26, with scores > or = 20 indicating abnormal eating attitudes. Bivariate analysis included independent Student t test, chi-square test, and Fisher's exact test. Multivariate logistic regression analysis was applied for the identification of the predictive factors, which were associated independently with abnormal eating attitudes. A 2-sided P value of less than .05 was considered statistically significant. The prevalence of abnormal eating attitudes was 16.7%. Multivariate logistic regression analysis demonstrated that females, urban residents, and those with a body mass index outside normal range, a perception of being overweight, body dissatisfaction, and a family member on a diet were independently related to abnormal eating attitudes. The results indicate that a proportion of Greek adolescents report abnormal eating attitudes and suggest that multiple factors contribute to the development of these attitudes. These findings are useful for further research into this topic and would be valuable in designing preventive interventions. Copyright 2010 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

  15. Mitochondrial Dynamics: Coupling Mitochondrial Fitness with Healthy Aging.

    PubMed

    Sebastián, David; Palacín, Manuel; Zorzano, Antonio

    2017-03-01

    Aging is associated with a decline in mitochondrial function and the accumulation of abnormal mitochondria. However, the precise mechanisms by which aging promotes these mitochondrial alterations and the role of the latter in aging are still not fully understood. Mitochondrial dynamics is a key process regulating mitochondrial function and quality. Altered expression of some mitochondrial dynamics proteins has been recently associated with aging and with age-related alterations in yeast, Caenorhabditis elegans, mice, and humans. Here, we review the link between alterations in mitochondrial dynamics, aging, and age-related impairment. We propose that the dysregulation of mitochondrial dynamics leads to age-induced accumulation of unhealthy mitochondria and contributes to alterations linked to aging, such as diabetes and neurodegeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Association of electrocardiogram abnormalities and incident heart failure events.

    PubMed

    Gencer, Baris; Butler, Javed; Bauer, Douglas C; Auer, Reto; Kalogeropoulos, Andreas; Marques-Vidal, Pedro; Applegate, William B; Satterfield, Suzanne; Harris, Tamara; Newman, Anne; Vittinghoff, Eric; Rodondi, Nicolas

    2014-06-01

    Unless effective preventive strategies are implemented, aging of the population will result in a significant worsening of the heart failure (HF) epidemic. Few data exist on whether baseline electrocardiographic (ECG) abnormalities can refine risk prediction for HF. We examined a prospective cohort of 2,915 participants aged 70 to 79 years without preexisting HF, enrolled between April 1997 and June 1998 in the Health, Aging, and Body Composition (Health ABC) study. Minnesota Code was used to define major and minor ECG abnormalities at baseline and at year 4 follow-up. Using Cox models, we assessed (1) the association between ECG abnormalities and incident HF and (2) the incremental value of adding ECG to the Health ABC HF Risk Score using the net reclassification index. At baseline, 380 participants (13.0%) had minor, and 620 (21.3%) had major ECG abnormalities. During a median follow-up of 11.4 years, 485 participants (16.6%) developed incident HF. After adjusting for the Health ABC HF Risk Score variables, the hazard ratio (HR) was 1.27 (95% CI 0.96-1.68) for minor and 1.99 (95% CI 1.61-2.44) for major ECG abnormalities. At year 4, 263 participants developed new and 549 had persistent abnormalities; both were associated with increased subsequent HF risk (HR 1.94, 95% CI 1.38-2.72 for new and HR 2.35, 95% CI 1.82-3.02 for persistent ECG abnormalities). Baseline ECG correctly reclassified 10.5% of patients with HF events, 0.8% of those without HF events, and 1.4% of the overall population. The net reclassification index across the Health ABC HF risk categories was 0.11 (95% CI 0.03-0.19). Among older adults, baseline and new ECG abnormalities are independently associated with increased risk of HF. The contribution of ECG screening for targeted prevention of HF should be evaluated in clinical trials. Copyright © 2014 Mosby, Inc. All rights reserved.

  17. Abnormal uterine bleeding in perimenopause.

    PubMed

    Goldstein, S R; Lumsden, M A

    2017-10-01

    Abnormal uterine bleeding is one of the commonest presenting complaints encountered in a gynecologist's office or primary-care setting. The wider availability of diagnostic tools has allowed prompt diagnosis and treatment of an increasing number of menstrual disorders in an office setting. This White Paper reviews the advantages and disadvantages of transvaginal ultrasound, blind endometrial sampling and diagnostic hysteroscopy. Once a proper diagnosis has been established, appropriate therapy may be embarked upon. Fortunately, only a minority of such patients will have premalignant or malignant disease. When bleeding is sufficient to cause severe anemia or even hypovolemia, prompt intervention is called for. In most of the cases, however, the abnormal uterine bleeding will be disquieting to the patient and significantly affect her 'quality of life'. Sometimes, reassurance and expectant management will be sufficient in such patients. Overall, however, in cases of benign disease, some intervention will be required. The use of oral contraceptive pills especially those with a short hormone-free interval, the insertion of the levonorgestrel intrauterine system, the incorporation of newer medical therapies including antifibrinolytic drugs and selective progesterone receptor modulators and minimally invasive treatments have made outpatient therapy increasingly effective. For others, operative hysteroscopy and endometrial ablation are proven therapeutic tools to provide both long- and short-term relief of abnormal uterine bleeding, thus avoiding, or deferring, hysterectomy.

  18. Intestinal Rotation Abnormalities and Midgut Volvulus.

    PubMed

    Langer, Jacob C

    2017-02-01

    Rotation abnormalities may be asymptomatic or may be associated with obstruction caused by bands, midgut volvulus, or associated atresia or web. The most important goal of clinicians is to determine whether the patient has midgut volvulus with intestinal ischemia, in which case an emergency laparotomy should be done. If the patient is not acutely ill, the next goal is to determine whether the patient has a narrow-based small bowel mesentery. In general, the outcomes for children with a rotation abnormality are excellent, unless there has been midgut volvulus with significant intestinal ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics

    NASA Astrophysics Data System (ADS)

    Linninger, Andreas A.; Tangen, Kevin; Hsu, Chih-Yang; Frim, David

    2016-01-01

    Cerebrospinal fluid (CSF) is not stagnant but displays fascinating oscillatory flow patterns inside the ventricular system and reversing fluid exchange between the cranial vault and spinal compartment. This review provides an overview of the current knowledge of pulsatile CSF motion. Observations contradicting classical views about its bulk production and clearance are highlighted. A clinical account of diseases of abnormal CSF flow dynamics, including hydrocephalus, syringomyelia, Chiari malformation type 1, and pseudotumor cerebri, is also given. We survey medical imaging modalities used to observe intracranial dynamics in vivo. Additionally, we assess the state of the art in predictive models of CSF dynamics. The discussion addresses open questions regarding CSF dynamics as they relate to the understanding and management of diseases.

  20. The accuracy of ultrasound in the diagnosis of congenital abnormalities.

    PubMed

    Munim, Shama; Nadeem, Salva; Khuwaja, Nadya Ali

    2006-01-01

    To determine the accuracy of ultrasound in the diagnosis of congenital abnormalities at the Aga Khan University Hospital, Karachi. The data of congenital abnormalities was obtained from the obstetrical database and medical records of all cases complicated by congenital abnormalities, delivering from January 2001 to December 2003 and was reviewed. Antenatal ultrasounds had been performed by operators with different level of experience. In addition this data was retrieved from the termination and Congenital anomaly register. A structured data collection form was used to collect information of different variables of interest. Congenital abnormalities, complicated 2.8% (n=170), of all deliveries, including all cases of termination of pregnancy, stillbirth and live births. Out of the total, 11.6% occurred in women above the age of 35 years. Consanguinity was found in 18.2% cases. Prenatal diagnosis was made in just under half of the cases (48.8%). Central nervous system and renal abnormalities were commonly diagnosed. However, facial defects, heart defects or skeletal defects were more commonly missed. Antenatal ultrasound successfully diagnosed foetal abnormalities in 48.8% of cases, and more than 90% Central Nervous system defects and renal abnormalities. In contrast about a quarter of Cardiac defects and none of the facial defects were detected. Based on these findings we recommend that the Sonologist should incorporate four chamber view of the heart and also look at the face carefully.

  1. Down's Syndrome and Leukemia: Mechanism of Additional Chromosomal Abnormalities

    ERIC Educational Resources Information Center

    And Others; Goh, Kong-oo

    1978-01-01

    Chromosomal abnormalities, some appearing in a stepwise clonal evoluation, were found in five Down's syndrome patients (35 weeks to 12 years old), four with acute leukemia and one with abnormal regulation of leukopoiesis. (Author/SBH)

  2. Stimulus-Induced Rhythmic, Periodic, or Ictal Discharges (SIRPIDs).

    PubMed

    Johnson, Emily L; Kaplan, Peter W; Ritzl, Eva K

    2018-05-01

    Stimulus-induced rhythmic, periodic, or ictal discharges (SIRPIDs) are a relatively common phenomenon found on prolonged electroencephalogram (EEG) monitoring that captures state changes and stimulation of critically ill patients. Common causes include hypoxic injury, traumatic brain injury, and hemorrhage, as well as toxic-metabolic disturbances. Some studies have shown an association between SIRPIDs and the presence of spontaneous electrographic seizures. Although the degree to which SIRPIDs should be treated with antiepileptic medications is unknown, the rare cases of functional imaging obtained in patients with SIRPIDs have not shown an increase in cerebral blood flow to suggest an active ictal process. Stimulus-induced rhythmic, periodic, or ictal discharges may reflect dysregulation of thalamo-cortical projections into abnormal or hyperexcitable cortex.

  3. Long memory of abnormal investor attention and the cross-correlations between abnormal investor attention and trading volume, volatility respectively

    NASA Astrophysics Data System (ADS)

    Fan, Xiaoqian; Yuan, Ying; Zhuang, Xintian; Jin, Xiu

    2017-03-01

    Taking Baidu Index as a proxy for abnormal investor attention (AIA), the long memory property in the AIA of Shanghai Stock Exchange (SSE) 50 Index component stocks was empirically investigated using detrended fluctuation analysis (DFA) method. The results show that abnormal investor attention is power-law correlated with Hurst exponents between 0.64 and 0.98. Furthermore, the cross-correlations between abnormal investor attention and trading volume, volatility respectively are studied using detrended cross-correlation analysis (DCCA) and the DCCA cross-correlation coefficient (ρDCCA). The results suggest that there are positive correlations between AIA and trading volume, volatility respectively. In addition, the correlations for trading volume are in general higher than the ones for volatility. By carrying on rescaled range analysis (R/S) and rolling windows analysis, we find that the results mentioned above are effective and significant.

  4. Skin - abnormally dark or light

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003242.htm Abnormally dark or light skin To use the sharing features ... The bronze color can range from light to dark (in fair-skinned people) with the degree of ...

  5. ACR appropriateness criteria(®) on abnormal vaginal bleeding.

    PubMed

    Bennett, Genevieve L; Andreotti, Rochelle F; Lee, Susanna I; Dejesus Allison, Sandra O; Brown, Douglas L; Dubinsky, Theodore; Glanc, Phyllis; Mitchell, Donald G; Podrasky, Ann E; Shipp, Thomas D; Siegel, Cary Lynn; Wong-You-Cheong, Jade J; Zelop, Carolyn M

    2011-07-01

    In evaluating a woman with abnormal vaginal bleeding, imaging cannot replace definitive histologic diagnosis but often plays an important role in screening, characterization of structural abnormalities, and directing appropriate patient care. Transvaginal ultrasound (TVUS) is generally the initial imaging modality of choice, with endometrial thickness a well-established predictor of endometrial disease in postmenopausal women. Endometrial thickness measurements of ≤5 mm and ≤4 mm have been advocated as appropriate upper threshold values to reasonably exclude endometrial carcinoma in postmenopausal women with vaginal bleeding; however, the best upper threshold endometrial thickness in the asymptomatic postmenopausal patient remains a subject of debate. Endometrial thickness in a premenopausal patient is a less reliable indicator of endometrial pathology since this may vary widely depending on the phase of menstrual cycle, and an upper threshold value for normal has not been well-established. Transabdominal ultrasound is generally an adjunct to TVUS and is most helpful when TVUS is not feasible or there is poor visualization of the endometrium. Hysterosonography may also allow for better delineation of both the endometrium and focal abnormalities in the endometrial cavity, leading to hysteroscopically directed biopsy or resection. Color and pulsed Doppler may provide additional characterization of a focal endometrial abnormality by demonstrating vascularity. MRI may also serve as an important problem-solving tool if the endometrium cannot be visualized on TVUS and hysterosonography is not possible, as well as for pretreatment planning of patients with suspected endometrial carcinoma. CT is generally not warranted for the evaluation of patients with abnormal bleeding, and an abnormal endometrium incidentally detected on CT should be further evaluated with TVUS. Copyright © 2011 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  6. Positional Magnetic Resonance Imaging for People With Ehlers-Danlos Syndrome or Suspected Craniovertebral or Cervical Spine Abnormalities: An Evidence-Based Analysis

    PubMed Central

    2015-01-01

    Background Ehlers-Danlos syndrome (EDS) is an inherited disorder affecting the connective tissue. EDS can manifest with symptoms attributable to the spine or craniovertebral junction (CVJ). In addition to EDS, numerous congenital, developmental, or acquired disorders can increase ligamentous laxity in the CVJ and cervical spine. Resulting abnormalities can lead to morbidity and serious neurologic complications. Appropriate imaging and diagnosis is needed to determine patient management and need for complex surgery. Some spinal abnormalities cause symptoms or are more pronounced while patients sit, stand, or perform specific movements. Positional magnetic resonance imaging (pMRI) allows imaging of the spine or CVJ with patients in upright, weight-bearing positions and can be combined with dynamic maneuvers, such as flexion, extension, or rotation. Imaging in these positions could allow diagnosticians to better detect spinal or CVJ abnormalities than recumbent MRI or even a combination of other available imaging modalities might allow. Objectives To determine the diagnostic impact and clinical utility of pMRI for the assessment of (a) craniovertebral or spinal abnormalities among people with EDS and (b) major craniovertebral or cervical spine abnormalities among symptomatic people. Data Sources A literature search was performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, and EBM Reviews, for studies published from January 1, 1998, to September 28, 2014. Review Methods Studies comparing pMRI to recumbent MRI or other available imaging modalities for diagnosis and management of spinal or CVJ abnormalities were reviewed. All studies of spinal or CVJ imaging in people with EDS were included as well as studies among people with suspected major CVJ or cervical spine abnormalities (cervical or craniovertebral spine instability, basilar invagination, cranial settling, cervical stenosis, spinal cord compression, Chiari

  7. The agreement between self-reported cervical smear abnormalities and screening programme records.

    PubMed

    Canfell, Karen; Beral, Valerie; Green, Jane; Cameron, Rebecca; Baker, Krys; Brown, Anna

    2006-01-01

    The Million Women Study is a cohort study of women aged 50-64 years in England and Scotland. As a component of the follow-up questionnaire, participants were asked to indicate if they had an abnormal cervical smear in the previous five years. This study compared self-reported cervical abnormalities with screening records obtained from the National Health Service Cervical Screening Programme. For 1944 randomly selected Million Women Study participants in Oxfordshire, screening records were assessed over a six-year period prior to the date of self-reporting. The six-year period was chosen to allow for errors in the recall of timing of abnormal smears. A total of 68 women (3.5%) had a record of at least one equivocal or abnormal smear within the last six years, whereas 49 women (2.5%) self-reported an abnormality. There was a strong trend for an increased probability of self-reporting a history of an abnormal smear as the severity of the recorded abnormality increased (P <0.001). For women with an NHS record of borderline dyskaryosis, mild dyskaryosis, or moderate dyskaryosis/severe dyskaryosis/invasive cancer, the proportions reporting an abnormality were 40%, 58% and 77%, respectively. For women with negative and inadequate smears, the proportion self-reporting an abnormality were 0.6% and 0.7%, respectively. These results indicate that among women whose screening programme records show an abnormal smear, the proportion self-reporting an abnormality increases with the severity of the recorded lesion. Almost all women with a record of negative or inadequate smear(s) correctly interpret the result and do not self-report an abnormality.

  8. Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers.

    PubMed

    Tay, Su Ann; Sanjay, Srinivasan

    2012-07-01

    An observational case report of electrophysiological abnormalities in a patient with anisomyopic amblyopia as a result of unilateral extensive myelinated retinal nerve fibers (MNFs) is illustrated. The electrophysiological readings revealed an abnormal pattern electroretinogram (PERG) but normal full-field electroretinogram readings in the affected eye. The visual-evoked potential was also undetectable in that eye. Our findings suggest that extensive MNFs can be associated with electrophysiological abnormalities, in particular the PERG, which can aid in diagnosing the cause of impaired vision when associated with amblyopia.

  9. Electrophysiological abnormalities associated with extensive myelinated retinal nerve fibers

    PubMed Central

    Tay, Su Ann; Sanjay, Srinivasan

    2012-01-01

    An observational case report of electrophysiological abnormalities in a patient with anisomyopic amblyopia as a result of unilateral extensive myelinated retinal nerve fibers (MNFs) is illustrated. The electrophysiological readings revealed an abnormal pattern electroretinogram (PERG) but normal full-field electroretinogram readings in the affected eye. The visual-evoked potential was also undetectable in that eye. Our findings suggest that extensive MNFs can be associated with electrophysiological abnormalities, in particular the PERG, which can aid in diagnosing the cause of impaired vision when associated with amblyopia. PMID:22824610

  10. Gains in accuracy from averaging ratings of abnormality

    NASA Astrophysics Data System (ADS)

    Swensson, Richard G.; King, Jill L.; Gur, David; Good, Walter F.

    1999-05-01

    Six radiologists used continuous scales to rate 529 chest-film cases for likelihood of five separate types of abnormalities (interstitial disease, nodules, pneumothorax, alveolar infiltrates and rib fractures) in each of six replicated readings, yielding 36 separate ratings of each case for the five abnormalities. Analyses for each type of abnormality estimated the relative gains in accuracy (area below the ROC curve) obtained by averaging the case-ratings across: (1) six independent replications by each reader (30% gain), (2) six different readers within each replication (39% gain) or (3) all 36 readings (58% gain). Although accuracy differed among both readers and abnormalities, ROC curves for the median ratings showed similar relative gains in accuracy. From a latent-variable model for these gains, we estimate that about 51% of a reader's total decision variance consisted of random (within-reader) errors that were uncorrelated between replications, another 14% came from that reader's consistent (but idiosyncratic) responses to different cases, and only about 35% could be attributed to systematic variations among the sampled cases that were consistent across different readers.

  11. Dendritic Arborization and Spine Dynamics Are Abnormal in the Mouse Model of MECP2 Duplication Syndrome

    PubMed Central

    Jiang, Minghui; Ash, Ryan T.; Baker, Steven A.; Suter, Bernhard; Ferguson, Andrew; Park, Jiyoung; Rudy, Jessica; Torsky, Sergey P.; Chao, Hsiao-Tuan; Zoghbi, Huda Y.

    2013-01-01

    MECP2 duplication syndrome is a childhood neurological disorder characterized by intellectual disability, autism, motor abnormalities, and epilepsy. The disorder is caused by duplications spanning the gene encoding methyl-CpG-binding protein-2 (MeCP2), a protein involved in the modulation of chromatin and gene expression. MeCP2 is thought to play a role in maintaining the structural integrity of neuronal circuits. Loss of MeCP2 function causes Rett syndrome and results in abnormal dendritic spine morphology and decreased pyramidal dendritic arbor complexity and spine density. The consequences of MeCP2 overexpression on dendritic pathophysiology remain unclear. We used in vivo two-photon microscopy to characterize layer 5 pyramidal neuron spine turnover and dendritic arborization as a function of age in transgenic mice expressing the human MECP2 gene at twice the normal levels of MeCP2 (Tg1; Collins et al., 2004). We found that spine density in terminal dendritic branches is initially higher in young Tg1 mice but falls below control levels after postnatal week 12, approximately correlating with the onset of behavioral symptoms. Spontaneous spine turnover rates remain high in older Tg1 animals compared with controls, reflecting the persistence of an immature state. Both spine gain and loss rates are higher, with a net bias in favor of spine elimination. Apical dendritic arbors in both simple- and complex-tufted layer 5 Tg1 pyramidal neurons have more branches of higher order, indicating that MeCP2 overexpression induces dendritic overgrowth. P70S6K was hyperphosphorylated in Tg1 somatosensory cortex, suggesting that elevated mTOR signaling may underlie the observed increase in spine turnover and dendritic growth. PMID:24336718

  12. Endocrine Abnormalities in Patients with Chronic Kidney Disease.

    PubMed

    Kuczera, Piotr; Adamczak, Marcin; Wiecek, Andrzej

    2015-01-01

    In patients with chronic kidney disease the alterations of the endocrine system may arise from several causes. The kidney is the site of degradation as well as synthesis of many different hormones. Moreover, a number of concomitant pathological conditions such as inflammation, metabolic acidosis and malnutrition may participate in the pathogenesis of endocrine abnormalities in this group of patients. The most pronounced endocrine abnormalities in patients with chronic kidney disease are the deficiencies of: calcitriol, testosterone, insulin-like growth factor and, erythropoietin (EPO). Additionally accumulation of several hormones, such as: prolactin, growth hormone and insulin frequently also occur. The clinical consequences of the abovementioned endocrine abnormalities are among others: anemia, infertility and bone diseases.

  13. NEW FRONTIER IN UNDERSTANDING THE MECHANISMS OF DEVELOPMENTAL ABNORMALITIES

    EPA Science Inventory

    Recent advancements in molecular developmental biology afford an opportunity to apply newly developed tools for understanding the mechanisms of both normal and abnormal development. lthough a number of agents have been identified as causing developmental abnormalities, knowledge ...

  14. Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

    PubMed Central

    Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

    2016-01-01

    Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo. PMID:27626081

  15. Syringomyelia and Craniocervical Junction Abnormalities in Chihuahuas.

    PubMed

    Kiviranta, A-M; Rusbridge, C; Laitinen-Vapaavuori, O; Hielm-Björkman, A; Lappalainen, A K; Knowler, S P; Jokinen, T S

    2017-11-01

    Chiari-like malformation (CM) and syringomyelia (SM) are widely reported in Cavalier King Charles Spaniels and Griffon Bruxellois dogs. Increasing evidence indicates that CM and SM also occur in other small and toy breed dogs, such as Chihuahuas. To describe the presence of SM and craniocervical junction (CCJ) abnormalities in Chihuahuas and to evaluate the possible association of CCJ abnormalities with SM. To describe CM/SM-related clinical signs and neurologic deficits and to investigate the association of CM/SM-related clinical signs with signalment, SM, or CCJ abnormalities. Fifty-three client-owned Chihuahuas. Prospective study. Questionnaire analyses and physical and neurologic examinations were obtained before magnetic resonance and computed tomography imaging. Images were evaluated for the presence of SM, CM, and atlantooccipital overlapping. Additionally, medullary kinking, dorsal spinal cord compression, and their sum indices were calculated. Scratching was the most common CM/SM-related clinical sign and decreased postural reaction the most common neurologic deficit in 73 and 87% of dogs, respectively. Chiari-like malformation and SM were present in 100 and 38% of dogs, respectively. Syringomyelia was associated with the presence of CM/SM-related clinical signs (P = 0.034), and medullary kinking and sum indices were higher in dogs with clinical signs (P = 0.016 and P = 0.007, respectively). Syringomyelia and CCJ abnormalities are prevalent in Chihuahuas. Syringomyelia was an important factor for the presence of CM/SM-related clinical signs, but many dogs suffered from similar clinical signs without being affected by SM, highlighting the clinical importance of CCJ abnormalities in Chihuahuas. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  16. Valence Scaling of Dynamic Facial Expressions Is Altered in High-Functioning Subjects with Autism Spectrum Disorders: An FMRI Study

    ERIC Educational Resources Information Center

    Rahko, Jukka S.; Paakki, Jyri-Johan; Starck, Tuomo H.; Nikkinen, Juha; Pauls, David L.; Katsyri, Jari V.; Jansson-Verkasalo, Eira M.; Carter, Alice S.; Hurtig, Tuula M.; Mattila, Marja-Leena; Jussila, Katja K.; Remes, Jukka J.; Kuusikko-Gauffin, Sanna A.; Sams, Mikko E.; Bolte, Sven; Ebeling, Hanna E.; Moilanen, Irma K.; Tervonen, Osmo; Kiviniemi, Vesa

    2012-01-01

    FMRI was performed with the dynamic facial expressions fear and happiness. This was done to detect differences in valence processing between 25 subjects with autism spectrum disorders (ASDs) and 27 typically developing controls. Valence scaling was abnormal in ASDs. Positive valence induces lower deactivation and abnormally strong activity in ASD…

  17. The effectiveness of airline pilot training for abnormal events.

    PubMed

    Casner, Stephen M; Geven, Richard W; Williams, Kent T

    2013-06-01

    To evaluate the effectiveness of airline pilot training for abnormal in-flight events. Numerous accident reports describe situations in which pilots responded to abnormal events in ways that were different from what they had practiced many times before. One explanation for these missteps is that training and testing for these skills have become a highly predictable routine for pilots who arrive to the training environment well aware of what to expect. Under these circumstances, pilots get plentiful practice in responding to abnormal events but may get little practice in recognizing them and deciding which responses to offer. We presented 18 airline pilots with three abnormal events that are required during periodic training and testing. Pilots were presented with each event under the familiar circumstances used during training and also under less predictable circumstances as they might occur during flight. When presented in the routine ways seen during training, pilots gave appropriate responses and showed little variability. However, when the abnormal events were presented unexpectedly, pilots' responses were less appropriate and showed great variability from pilot to pilot. The results suggest that the training and testing practices used in airline training may result in rote-memorized skills that are specific to the training situation and that offer modest generalizability to other situations. We recommend a more complete treatment of abnormal events that allows pilots to practice recognizing the event and choosing and recalling the appropriate response. The results will aid the improvement of existing airline training practices.

  18. Histopathological pattern of abnormal uterine bleeding in endometrial biopsies.

    PubMed

    Vaidya, S; Lakhey, M; Vaidya, S; Sharma, P K; Hirachand, S; Lama, S; KC, S

    2013-03-01

    Abnormal uterine bleeding is a common presenting complaint in gyanecology out patient department. Histopathological evaluation of the endometrial samples plays a significant role in the diagnosis of abnormal uterine bleeding. This study was carried out to determine the histopathological pattern of the endometrium in women of various age groups presenting with abnormal uterine bleeding. Endometrial biopsies and curettings of patients presenting with abnormal uterine bleeding was retrospectively studied. A total of 403 endometrial biopsies and curettings were analyzed. The age of the patients ranged from 18 to 70 years. Normal cyclical endometrium was seen in 165 (40.94%) cases, followed by 54 (13.40%) cases of disordered proliferative endometrium and 44 (10.92%) cases of hyperplasia. Malignancy was seen in 10 (2.48%) cases. Hyperplasia and malignancy were more common in the perimenopausal and postmenopausal age groups. Histopathological examination of endometrial biopsies and curettings in patients presenting with abnormal uterine bleeding showed a wide spectrum of changes ranging from normal endometrium to malignancy. Endometrial evaluation is specially recommended in women of perimenopausal and postmenopausal age groups presenting with AUB, to rule out a possibility of any preneoplastic condition or malignancy.

  19. Adverse Pregnancy Outcomes after Abnormal First Trimester Screening for Aneuploidy

    PubMed Central

    Goetzl, Laura

    2010-01-01

    Women with abnormal first trimester screening but with a normal karyotype are at risk for adverse pregnancy outcomes. A nuchal translucency >3.5mm is associated with an increased risk of subsequent pregnancy loss, fetal infection, fetal heart abnormalities and other structural abnormalities. Abnormal first trimester analytes are also associated with adverse pregnancy outcomes but the predictive value is less impressive. As a single marker, PAPP-A <1st%ile has a good predictive value for subsequent fetal growth restriction. Women with PAPP-A<5th%ile should undergo subsequent risk assessment with routine MSAFP screening with the possible addition of uterine artery PI assessment in the midtrimester. PMID:20638576

  20. Sporadic adult onset dystonia: sensory abnormalities as an endophenotype in unaffected relatives

    PubMed Central

    Walsh, Richard; O'Dwyer, John P; Sheikh, Ifthikar H; O'Riordan, Sean; Lynch, Tim; Hutchinson, Michael

    2007-01-01

    Background Most patients with adult onset primary torsion dystonia (AOPTD) have the sporadic form of the disease. They may however be the only manifesting family members of a poorly penetrant genetic disorder. Sensory changes, including structural abnormalities of the primary sensory cortex, are found in AOPTD. Spatial discrimination threshold (SDT), a measure of sensory cortical organisation, is abnormal in AOPTD and in unaffected relatives of patients with familial AOPTD. Our hypothesis was that abnormal SDTs might be found in unaffected relatives of patients with sporadic AOPTD. Methods SDTs were assessed at the index finger bilaterally by a grating orientation task. Normal age related SDTs were derived from 141 control subjects aged 20–64 years. SDTs were considered abnormal when greater than 2.5 SD above the control mean. In total, 105 of 171 (61%) eligible unaffected siblings and offspring of patients with cervical dystonia had SDT examined. Results Fourteen of 48 siblings (29%) and 10 of 57 (18%) offspring were found to have an abnormal SDT. Only five of the 20 patients examined had abnormal SDTs. In 11 of the 25 families, no abnormality was found in an unaffected relative. In the 14 families where at least one unaffected relative had an abnormal SDT, 14 of 37 siblings (38%) and 10 of 33 offspring (30%) had abnormal SDTs. Conclusion Sensory abnormalities found in unaffected relatives of patients with apparently sporadic AOPTD may be a surrogate marker for the carriage of an abnormal gene. PMID:17702779

  1. The handicap of abnormal colour vision.

    PubMed

    Cole, Barry L

    2004-07-01

    All people with abnormal colour vision, except for a few mildly affected deuteranomals, report that they experience problems with colour in everyday life and at work. Contemporary society presents them with increasing problems because colour is now so widely used in printed materials and in computer displays. Equal opportunity law gives them protection against unfair discrimination in employment, so a decision to exclude a person from employment on the grounds of abnormal colour vision must now be well supported by good evidence and sound argument. This paper reviews the investigations that have contributed to understanding the nature and consequences of the problems they have. All those with abnormal colour vision are at a disadvantage with comparative colour tasks that involve precise matching of colours or discrimination of fine colour differences either because of their loss of colour discrimination or anomalous perception of metamers. The majority have problems when colour is used to code information, in man-made colour codes and in naturally occurring colour codes that signal ripeness of fruit, freshness of meat or illness. They can be denied the benefit of colour to mark out objects and organise complex visual displays. They may be unreliable when a colour name is used as an identifier. They are slower and less successful in search when colour is an attribute of the target object or is used to organise the visual display. Because those with the more severe forms of abnormal colour vision perceive a very limited gamut of colours, they are at a disadvantage in the pursuit and appreciation of those forms of art that use colour.

  2. Transvaginal Ultrasound for the Diagnosis of Abnormal Uterine Bleeding.

    PubMed

    Wheeler, Karen C; Goldstein, Steven R

    2017-03-01

    Transvaginal ultrasound is the first-line imaging test for the evaluation of abnormal uterine bleeding in both premenopausal and postmenopausal women. Transvaginal ultrasound can be used to diagnose structural causes of abnormal bleeding such as polyps, adenomyosis, leiomyomas, hyperplasia, and malignancy, and can also be beneficial in making the diagnosis of ovulatory dysfunction. Traditional 2-dimensional imaging is often enhanced by the addition of 3-dimension imaging with coronal reconstruction and saline infusion sonohysterography. In this article we discuss specific ultrasound findings and technical considerations useful in the diagnosis of abnormal uterine bleeding.

  3. [Hysteroscopy clinic: diagnostic and therapeutic method in abnormal uterine bleeding].

    PubMed

    Alanis Fuentes, José; Obregón Zegarra, Eva Haydee

    2012-12-01

    Abnormal uterine bleeding is a public health problem prevalence exceeded only by abnormal vaginal discharge as a reason for medical consultation. To describe the findings reported by the Hysteroscopy clinic of the Hospital GEA Gonzalez on patients with Abnormal Uterine bleeding diagnosis. Retrospective, transversal, descriptive study. The total 2546 records of those patient that were evaluated by Office Hysteroscopic between January 2007 and December 2008 on the Hysteroscopy Clinic of Hospital Manuel GEA Gonzalez, then we selected the 1482 records of those patients that were sended because of an Abnormal Uterine bleeding condition. We descrive the frequencies of the diagnosis and its interrelation with the age of the patients. We also report the therapeutical interventions during office hysteroscopy. The mean age of the patients was 42.15 +/- 9.30 years (from 12 a 92 years); the age groups of patients that belonged to 40-44 years and 45-49 years are the most frequent patient and they represent the 25% y el 23.3% of the records. The abnormal findings occurred on the 66% de of the patients. Those patients of 65 years old and older do not have any report of normal cavities, all of then have abnormal findings. The leiomyoma (26.9%) and the endometrial polyps (27.3%) were the most frequent findings. The postmenopausal bleeding had a rate of 90.9% abnormal findings and in this group of patients the most frequent diagnosis was atrophic endometrium (32.2%) and polyps (24.3%). Besides that the office hysteroscopy show its therapeutical usefulness because of the 67% and 77.5% of polipectomy perform for endometrial and cervical polyps respectively The office Hysteroscopy is a well tolerated diagnosis and therapeutic method that is useful for any women with abnormal uterine bleeding condition and it is the ideal technique for the examination of abnormal uterine bleeding in postmenopausal women... The office hysteroscopy is a efficient cost-effective and cost-benefic method for

  4. Craniofacial abnormalities among patients with Edwards Syndrome

    PubMed Central

    Rosa, Rafael Fabiano M.; Rosa, Rosana Cardoso M.; Lorenzen, Marina Boff; Zen, Paulo Ricardo G.; Graziadio, Carla; Paskulin, Giorgio Adriano

    2013-01-01

    OBJECTIVE To determine the frequency and types of craniofacial abnormalities observed in patients with trisomy 18 or Edwards syndrome (ES). METHODS This descriptive and retrospective study of a case series included all patients diagnosed with ES in a Clinical Genetics Service of a reference hospital in Southern Brazil from 1975 to 2008. The results of the karyotypic analysis, along with clinical data, were collected from medical records. RESULTS: The sample consisted of 50 patients, of which 66% were female. The median age at first evaluation was 14 days. Regarding the karyotypes, full trisomy of chromosome 18 was the main alteration (90%). Mosaicism was observed in 10%. The main craniofacial abnormalities were: microretrognathia (76%), abnormalities of the ear helix/dysplastic ears (70%), prominent occiput (52%), posteriorly rotated (46%) and low set ears (44%), and short palpebral fissures/blepharophimosis (46%). Other uncommon - but relevant - abnormalities included: microtia (18%), orofacial clefts (12%), preauricular tags (10%), facial palsy (4%), encephalocele (4%), absence of external auditory canal (2%) and asymmetric face (2%). One patient had an initial suspicion of oculo-auriculo-vertebral spectrum (OAVS) or Goldenhar syndrome. CONCLUSIONS: Despite the literature description of a characteristic clinical presentation for ES, craniofacial alterations may be variable among these patients. The OAVS findings in this sample are noteworthy. The association of ES with OAVS has been reported once in the literature. PMID:24142310

  5. The impact of abnormal autoimmune function on reproduction: maternal and fetal consequences.

    PubMed

    Gleicher, Norbert; Weiner, Rebecca; Vietzke, Mary

    2006-11-01

    The impact of abnormal autoimmune function on reproductive success has remained a highly controversial issue. This is, at least partially, due to the relative lack of demographic data from women with established autoimmune diseases. We, therefore, investigated 163 women with proven autoimmune diseases and 73 controls in a demographic study of reproductive success and impact of abnormal autoimmunity on pregnancy and offspring. Women with autoimmune diseases experienced fewer pregnancies overall (p=0.04) and fewer pregnancy losses (p=0.05). Offspring from women with autoimmune diseases demonstrated a significantly increased prevalence of confirmed autoimmune diseases (p=0.04; OR 3.759; 95%CL 1.04-1.27), which increased further if suspected, but not yet confirmed, cases were added (p=0.001; OR 8.592; 95%CL 1.05-55.0). Women with autoimmune diseases exhibited a trend towards lower cesarean section delivery during their own birth and a significantly increased prevalence of disease in vaginally delivered offspring (p=0.014; OR 6.041; 95%CL 1.32-38.22). Autoimmune diseases impair female fecundity even before the diseases become clinically overt. Offspring are at increased risk to develop autoimmune diseases, though they may differ from those of their mothers. This risk appears to correlate with mode of delivery and may be the consequence of varying cell traffic dynamics with vaginal and cesarean section deliveries.

  6. Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?

    PubMed

    Raaijmakers, R; Noordam, C; Noonan, J A; Croonen, E A; van der Burgt, C J A M; Draaisma, J M T

    2008-12-01

    Of all patients with Noonan syndrome, 50-90% have one or more congenital heart defects. The most frequent occurring are pulmonary stenosis (PS) and hypertrophic cardiomyopathy. The electrocardiogram (ECG) of a patient with Noonan syndrome often shows a characteristic pattern, with a left axis deviation, abnormal R/S ratio over the left precordium, and an abnormal Q wave. The objective of this study was to determine if these ECG characteristics are an independent feature of the Noonan syndrome or if they are related to the congenital heart defect. A cohort study was performed with 118 patients from two university hospitals in the United States and in The Netherlands. All patients were diagnosed with definite Noonan syndrome and had had an ECG and echocardiography. Sixty-nine patients (58%) had characteristic abnormalities of the ECG. In the patient group without a cardiac defect (n = 21), ten patients had a characteristic ECG abnormality. There was no statistical relationship between the presence of a characteristic ECG abnormality and the presence of a cardiac defect (p = 0.33). Patients with hypertrophic cardiomyopathy had more ECG abnormalities in total (p = 0.05), without correlation with a specific ECG abnormality. We conclude that the ECG features in patients with Noonan syndrome are characteristic for the syndrome and are not related to a specific cardiac defect. An ECG is very useful in the diagnosis of Noonan syndrome; every child with a Noonan phenotype should have an ECG and echocardiogram for evaluation.

  7. Radiographic abnormalities among construction workers exposed to quartz containing dust

    PubMed Central

    Tjoe, N; Burdorf, A; Parker, J; Attfield, M; van Duivenbooden, C; Heederik, D

    2003-01-01

    Background: Construction workers are exposed to quartz containing respirable dust, at levels that may cause fibrosis in the lungs. Studies so far have not established a dose-response relation for radiographic abnormalities for this occupational group. Aims: To measure the extent of radiographic abnormalities among construction workers primarily exposed to quartz containing respirable dust. Methods: A cross sectional study on radiographic abnormalities indicative of pneumoconiosis was conducted among 1339 construction workers mainly involved in grinding, (jack)-hammering, drilling, cutting, sawing, and polishing. Radiological abnormalities were determined by median results of the 1980 International Labour Organisation system of three certified "B" readers. Questionnaires were used for assessment of occupational history, presence of respiratory diseases, and symptoms and smoking habits. Results: An abnormality of ILO profusion category 1/0 and greater was observed on 10.2% of the chest radiographs, and profusion category of 1/1 or greater on 2.9% of the radiographs. The average duration of exposure of this group was 19 years and the average age was 42. The predominant type of small opacities (irregularly shaped) is presumably indicative of mixed dust pneumoconiosis. The prevalence of early signs of nodular silicosis (small rounded opacities of category 1/0 or greater) was low (0.8%). Conclusions: The study suggests an elevated risk of radiographic abnormalities among these workers with expected high exposure. An association between radiographic abnormalities and cumulative exposure to quartz containing dust from construction sites was observed, after correction for potentially confounding variables. PMID:12771392

  8. Visualizing how cancer chromosome abnormalities form in living cells

    Cancer.gov

    For the first time, scientists have directly observed events that lead to the formation of a chromosome abnormality that is often found in cancer cells. The abnormality, called a translocation, occurs when part of a chromosome breaks off and becomes attac

  9. Hemorheological abnormalities in human arterial hypertension

    NASA Astrophysics Data System (ADS)

    Lo Presti, Rosalia; Hopps, Eugenia; Caimi, Gregorio

    2014-05-01

    Blood rheology is impaired in hypertensive patients. The alteration involves blood and plasma viscosity, and the erythrocyte behaviour is often abnormal. The hemorheological pattern appears to be related to some pathophysiological mechanisms of hypertension and to organ damage, in particular left ventricular hypertrophy and myocardial ischemia. Abnormalities have been observed in erythrocyte membrane fluidity, explored by fluorescence spectroscopy and electron spin resonance. This may be relevant for red cell flow in microvessels and oxygen delivery to tissues. Although blood viscosity is not a direct target of antihypertensive therapy, the rheological properties of blood play a role in the pathophysiology of arterial hypertension and its vascular complications.

  10. Congenital abnormalities associated with extrahepatic portal hypertension.

    PubMed Central

    Odièvre, M; Pigé, G; Alagille, D

    1977-01-01

    Congenital abnormalities were present in 12 out of 30 (40%) children with extrahepatic portal hypertension of unknown cause, but in only 2 out of 17 (12%) children with extnahepatic portal hypertension secondary to umbilical vein catheterization or omphalitis. The most frequent abnormalities in this series and in published reports were atrial septal defect, malformation of the biliary tract, and anomalous inferior vena cava. These findings are consistent with the view that some cases with extrahepatic portal hypertension are congenital in origin. PMID:869567

  11. Abnormal uterine bleeding in reproductive-aged women.

    PubMed

    Matthews, Michelle L

    2015-03-01

    Abnormal uterine bleeding is a common medical condition with several causes. The International Federation of Gynecology and Obstetrics published guidelines in 2011 to develop universally accepted nomenclature and a classification system. In addition, the American College of Obstetrics and Gynecology recently updated recommendations on evaluation of abnormal uterine bleeding and indications for endometrial biopsies. This article reviews both medical and surgical treatments, including meta-analysis reviews of the most effective treatment options. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. An abattoir survey of equine dental abnormalities in Queensland, Australia.

    PubMed

    Chinkangsadarn, T; Wilson, G J; Greer, R M; Pollitt, C C; Bird, P S

    2015-06-01

    A cadaver study to estimate the prevalence of dental disorders in horses presented at an abattoir in Queensland, Australia. Cadaver heads at a Queensland abattoir were examined for the presence of dental abnormalities and categorised into age groups. The prevalence of abnormalities was analysed by binomial observation of observed proportion, Pearson's Chi-square test or Fisher's exact correlation test. Strength of association was evaluated using Cramer's V test. Heads from horses (n=400) estimated to be between 1 and 30 years of age were placed into four age groups. The most common abnormalities were sharp enamel points (55.3%) and hooks (43%). The highest frequency of dental diseases and abnormalities were in horses 11-15 years old (97.5%). Common abnormalities were found in all groups and the prevalence increased with age. This study suggests that all horses should have regular complete dental examinations to detect and treat dental disorders in order to limit more severe dental pathologies later in life. © 2015 Australian Veterinary Association.

  13. Volume estimation of brain abnormalities in MRI data

    NASA Astrophysics Data System (ADS)

    Suprijadi, Pratama, S. H.; Haryanto, F.

    2014-02-01

    The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

  14. Fetal Alcohol Spectrum Disorders and Abnormal Neuronal Plasticity

    PubMed Central

    Medina, Alexandre E.

    2012-01-01

    The ingestion of alcohol during pregnancy can result in a group of neurobehavioral abnormalities collectively known as fetal alcohol spectrum disorders (FASD). During the past decade, studies using animal models indicated that early alcohol exposure can dramatically affect neuronal plasticity, an essential property of the central nervous system responsible for the normal wiring of the brain and involved in processes such as learning and memory. The abnormalities in neuronal plasticity caused by alcohol can explain many of the neurobehavioral deficits observed in FASD. Conversely, improving neuronal plasticity may have important therapeutic benefits. In this review, the author discuss the mechanisms that lead to these abnormalities and comment on recent pharmacological approaches that have been showing promising results in improving neuronal plasticity in FASD. PMID:21383101

  15. Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

    PubMed Central

    Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

    2011-01-01

    The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

  16. 42 CFR 37.53 - Notification of abnormal roentgenographic findings.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... suggesting, enlarged heart, tuberculosis, lung cancer, or any other significant abnormal findings other than... files and the most recent examination was interpreted to show enlarged heart, tuberculosis, cancer... findings suggesting, abnormality of cardiac shape or size, tuberculosis, lung cancer, or any other...

  17. XYY chromosome abnormality in sexual homicide perpetrators.

    PubMed

    Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

    2006-03-05

    In a retrospective investigation of the court reports about sexual homicide perpetrators chromosome analysis had been carried out in 13 of 166 (7.8%) men. Three men (1.8%) with XYY chromosome abnormality were found. This rate is much higher than that found in unselected samples of prisoners (0.7-0.9%) or in the general population (0.01%). The three men had shown prepubescent abnormalities, school problems, and had suffered from physical abuse. The chromosome analysis in all cases had been carried out in connection with the forensic psychiatric court report due to the sexual homicide. However, two men had earlier psychiatric referrals. All were diagnosed as sexual sadistic, showed a psychopathic syndrome or psychopathy according to the Psychopathy Checklist-Revised [Hare RD, 1991, The Hare Psychopathy Checklist-Revised, Toronto, Ontario, Canada: Multi-Health Systems]. Two were multiple murderers. Especially forensic psychiatrists should be vigilant of the possibility of XYY chromosome abnormalities in sexual offenders. (c) 2006 Wiley-Liss, Inc.

  18. Prediction of vascular abnormalities on CT angiography in patients with acute headache.

    PubMed

    Alons, Imanda M E; Goudsmit, Ben F J; Jellema, Korné; van Walderveen, Marianne A A; Wermer, Marieke J H; Algra, Ale

    2018-05-09

    Patients with acute headache increasingly undergo CT-angiography (CTA) to evaluate underlying vascular causes. The aim of this study is to determine clinical and non-contrast CT (NCCT) criteria to select patients who might benefit from CTA. We retrospectively included patients with acute headache who presented to the emergency department of an academic medical center and large regional teaching hospital and underwent NCCT and CTA. We identified factors that increased the probability of finding a vascular abnormality on CTA, performed multivariable regression analyses and determined discrimination with the c-statistic. A total of 384 patients underwent NCCT and CTA due to acute headache. NCCT was abnormal in 194 patients. Among these, we found abnormalities in 116 cases of which 99 aneurysms. In the remaining 190 with normal NCCT we found abnormalities in 12 cases; four unruptured aneurysms, three cerebral venous thrombosis', two reversible cerebral vasoconstriction syndromes, two cervical arterial dissections and one cerebellar infarction. In multivariable analysis abnormal NCCT, lowered consciousness and presentation within 6 hr of headache onset were independently associated with abnormal CTA. The c-statistic of abnormal NCCT alone was 0.80 (95% CI: 0.75-0.80), that also including the other two variables was 0.84 (95% CI: 0.80-0.88). If NCCT was normal no other factors could help identify patients at risk for abnormalities. In patients with acute headache abnormal NCCT is the strongest predictor of a vascular abnormality on CTA. If NCCT is normal no other predictors increase the probability of finding an abnormality on CTA and diagnostic yield is low. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

  19. [Congenital abnormalities of the aorta in children and adolescents].

    PubMed

    Eichhorn, J G; Ley, S

    2007-11-01

    Aortic abnormalities are common cardiovascular malformations accounting for 15-20% of all congenital heart disease. Ultrafast CT and MR imaging are noninvasive, accurate and robust techniques that can be used in the diagnosis of aortic malformations. While their sensitivity in detecting vascular abnormalities seems to be as good as that of conventional catheter angiocardiography, at over 90%, they are superior in the diagnosis of potentially life-threatening complications, such as tracheal, bronchial, or esophageal compression. It has been shown that more than 80% of small children with aortic abnormalities benefit directly from the use of noninvasive imaging: either cardiac catheterization is no longer necessary or radiation doses and periods of general anesthesia for interventional catheterization procedures can be much reduced. The most important congenital abnormalities of the aorta in children and adolescents are presented with reference to examples, and the value of CT and MR angiography is documented.

  20. Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

    PubMed Central

    Zhou, Joanne; Butler, Erin E.; Rose, Jessica

    2017-01-01

    Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP. PMID:28367118

  1. 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.

  2. Pediatric Patients Discharged from the Emergency Department with Abnormal Vital Signs.

    PubMed

    Winter, Josephine; Waxman, Michael J; Waterman, George; Ata, Ashar; Frisch, Adam; Collins, Kevin P; King, Christopher

    2017-08-01

    Children often present to the emergency department (ED) with minor conditions such as fever and have persistently abnormal vital signs. We hypothesized that a significant portion of children discharged from the ED would have abnormal vital signs and that those discharged with abnormal vital signs would experience very few adverse events. We performed a retrospective chart review encompassing a 44-month period of all pediatric patients (aged two months to 17 years) who were discharged from the ED with an abnormal pulse rate, respiratory rate, temperature, or oxygen saturation. We used a local quality assurance database to identify pre-defined adverse events after discharge in this population. Our primary aim was to determine the proportion of children discharged with abnormal vital signs and the frequency and nature of adverse events. Additionally, we performed a sub-analysis comparing the rate of adverse events in children discharged with normal vs. abnormal vital signs, as well as a standardized review of the nature of each adverse event. Of 33,185 children discharged during the study period, 5,540 (17%) of these patients had at least one abnormal vital sign. There were 24/5,540 (0.43%) adverse events in the children with at least one abnormal vital sign vs. 47/27,645 (0.17%) adverse events in the children with normal vital signs [relative risk = 2.5 (95% confidence interval, 1.6 to 2.4)].However, upon review of each adverse event we found only one case that was related to the index visit, was potentially preventable by a 23-hour hospital observation, and caused permanent disability. In our study population, 17% of the children were discharged with at least one abnormal vital sign, and there were very few adverse (0.43%) events associated with this practice. Heart rate was the most common abnormal vital sign leading to an adverse event. Severe adverse events that were potentially related to the abnormal vital sign(s) were exceedingly rare. Additional research is

  3. Managing abnormal eating behaviours in frontotemporal lobar degeneration patients with topiramate.

    PubMed

    Shinagawa, Shunichiro; Tsuno, Norifumi; Nakayama, Kazuhiko

    2013-03-01

    Abnormal eating behaviours are specific to frontotemporal lobar degeneration and increase caregiver burden. Topiramate, an anticonvulsant, suppresses cravings for alcohol and other substances and is a potential treatment for binge eating. However, there are few reports on topiramate efficacy for abnormal eating behaviours in frontotemporal lobar degeneration patients. We present three Japanese frontotemporal lobar degeneration patients with abnormal eating behaviours. Topiramate was effective, especially for compulsive eating, in cases with distinct lobar atrophy, but not for all abnormal eating behaviours. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

  4. Axonal abnormalities in vanishing white matter.

    PubMed

    Klok, Melanie D; Bugiani, Marianna; de Vries, Sharon I; Gerritsen, Wouter; Breur, Marjolein; van der Sluis, Sophie; Heine, Vivi M; Kole, Maarten H P; Baron, Wia; van der Knaap, Marjo S

    2018-04-01

    We aimed to study the occurrence and development of axonal pathology and the influence of astrocytes in vanishing white matter. Axons and myelin were analyzed using electron microscopy and immunohistochemistry on Eif2b4 and Eif2b5 single- and double-mutant mice and patient brain tissue. In addition, astrocyte-forebrain co-culture studies were performed. In the corpus callosum of Eif2b5- mutant mice, myelin sheath thickness, axonal diameter, and G-ratio developed normally up to 4 months. At 7 months, however, axons had become thinner, while in control mice axonal diameters had increased further. Myelin sheath thickness remained close to normal, resulting in an abnormally low G-ratio in Eif2b5- mutant mice. In more severely affected Eif2b4-Eif2b5 double-mutants, similar abnormalities were already present at 4 months, while in milder affected Eif2b4 mutants, few abnormalities were observed at 7 months. Additionally, from 2 months onward an increased percentage of thin, unmyelinated axons and increased axonal density were present in Eif2b5 -mutant mice. Co-cultures showed that Eif2b5 mutant astrocytes induced increased axonal density, also in control forebrain tissue, and that control astrocytes induced normal axonal density, also in mutant forebrain tissue. In vanishing white matter patient brains, axons and myelin sheaths were thinner than normal in moderately and severely affected white matter. In mutant mice and patients, signs of axonal transport defects and cytoskeletal abnormalities were minimal. In vanishing white matter, axons are initially normal and atrophy later. Astrocytes are central in this process. If therapy becomes available, axonal pathology may be prevented with early intervention.

  5. 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

  6. Abnormal centromere-chromatid apposition (ACCA) and Peters' anomaly.

    PubMed

    Wertelecki, W; Dev, V G; Superneau, D W

    1985-08-01

    Abnormal centromere-chromatid apposition (ACCA) was noted in a patient with Peters' anomaly. Previous reports of ACCA emphasized its association with tetraphocomelia and other congenital malformations (Roberts, SC Phocomelia, Pseudothalidomide Syndromes). This report expands the array of congenital malformations associated with ACCA and emphasizes the diagnostic importance of ocular defects for the ascertainment of additional cases of ACCA and its possible relationship with abnormal cell division.

  7. Leptin alters somatosensory thalamic networks by decreasing gaba release from reticular thalamic nucleus and action potential frequency at ventrobasal neurons.

    PubMed

    Perissinotti, Paula P; Rivero-Echeto, María Celeste; Garcia-Rill, Edgar; Bisagno, Verónica; Urbano, Francisco J

    2018-06-01

    Leptin is an adipose-derived hormone that controls appetite and energy expenditure. Leptin receptors are expressed on extra-hypothalamic ventrobasal (VB) and reticular thalamic (RTN) nuclei from embryonic stages. Here, we studied the effects of pressure-puff, local application of leptin on both synaptic transmission and action potential properties of thalamic neurons in thalamocortical slices. We used whole-cell patch-clamp recordings of thalamocortical VB neurons from wild-type (WT) and leptin-deficient obese (ob/ob) mice. We observed differences in VB neurons action potentials and synaptic currents kinetics when comparing WT vs. ob/ob. Leptin reduced GABA release onto VB neurons throughout the activation of a JAK2-dependent pathway, without affecting excitatory glutamate transmission. We observed a rapid and reversible reduction by leptin of the number of action potentials of VB neurons via the activation of large conductance Ca 2+ -dependent potassium channels. These leptin effects were observed in thalamocortical slices from up to 5-week-old WT but not in leptin-deficient obese mice. Results described here suggest the existence of a leptin-mediated trophic modulation of thalamocortical excitability during postnatal development. These findings could contribute to a better understanding of leptin within the thalamocortical system and sleep deficits in obesity.

  8. Neuroimaging evidence of brain abnormalities in mastocytosis.

    PubMed

    Boddaert, N; Salvador, A; Chandesris, M O; Lemaître, H; Grévent, D; Gauthier, C; Naggara, O; Georgin-Lavialle, S; Moura, D S; Munsch, F; Jaafari, N; Zilbovicius, M; Lortholary, O; Gaillard, R; Hermine, O

    2017-08-08

    Mastocytosis is a rare disease in which chronic symptoms are related to mast cell accumulation and activation. Patients can display depression-anxiety-like symptoms and cognitive impairment. The pathophysiology of these symptoms may be associated with tissular mast cell infiltration, mast cell mediator release or both. The objective of this study is to perform morphological or functional brain analyses in mastocytosis to identify brain changes associated with this mast cell disorder. We performed a prospective and monocentric comparative study to evaluate the link between subjective psycho-cognitive complaints, psychiatric evaluation and objective medical data using magnetic resonance imaging with morphological and perfusion sequences (arterial spin-labeled perfusion) in 39 patients with mastocytosis compared with 33 healthy controls. In the test cohort of 39 mastocytosis patients with psycho-cognitive complaints, we found that 49% of them had morphological brain abnormalities, mainly abnormal punctuated white matter abnormalities (WMA). WMA were equally frequent in cutaneous mastocytosis patients and indolent forms of systemic mastocytosis patients (42% and 41% of patients with WMA, respectively). Patients with WMA showed increased perfusion in the putamen compared with patients without WMA and with healthy controls. Putamen perfusion was also negatively correlated with depression subscores. This study demonstrates, for we believe the first time, a high prevalence of morphological and functional abnormalities in the brains of mastocytosis patients with neuropsychiatric complaints. Further studies are required to determine the mechanism underpinning this association and to ascertain its specificity.

  9. Radiation induced abnormalities in early in vitro mouse embryos

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

    Kirkpatrick, J.F.

    1973-08-01

    Female mice were superovulated and mated, and the two-cell embryos were collected and cultured in vitro. The embryos were exposed to x-irradiation (0 to 491 rads) during the two-cell stage before the appearance of the next cleavage plate, placed in new unirradiated culture medium and observed during subsequent development. Morphological abnormalities, which occurred as a result of irradiation, included fragmentation, disintegration, granlation, incomplete cleavage, cleavage cessation, nuclear degeneration and pycnosis and cytoplasmic vacuolization. There was no damage to the zona pellucida. The types of abnormalities indicate an agreement with the results of previous in vivo studies. A distinct correlation existedmore » between morphological abnormalities and embryo death. The greatest number of abnormalities resulted within five hours following irradiation, but increased through 20 hours post-exposure. At doses above 300 rads, the magnitude of damage was greater in the in vitro embryos than that shown in previous in vivo studies. (auth)« less

  10. Gross Motor Development, Movement Abnormalities, and Early Identification of Autism

    PubMed Central

    Young, Gregory S.; Goldring, Stacy; Greiss-Hess, Laura; Herrera, Adriana M.; Steele, Joel; Macari, Suzanne; Hepburn, Susan; Rogers, Sally J.

    2015-01-01

    Gross motor development (supine, prone, rolling, sitting, crawling, walking) and movement abnormalities were examined in the home videos of infants later diagnosed with autism (regression and no regression subgroups), developmental delays (DD), or typical development. Group differences in maturity were found for walking, prone, and supine, with the DD and Autism-No Regression groups both showing later developing motor maturity than typical children. The only statistically significant differences in movement abnormalities were in the DD group; the two autism groups did not differ from the typical group in rates of movement abnormalities or lack of protective responses. These findings do not replicate previous investigations suggesting that early motor abnormalities seen on home video can assist in early identification of autism. PMID:17805956

  11. Normal and abnormal human vestibular ocular function

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.

    1986-01-01

    The major motivation of this research is to understand the role the vestibular system plays in sensorimotor interactions which result in spatial disorientation and motion sickness. A second goal was to explore the range of abnormality as it is reflected in quantitative measures of vestibular reflex responses. The results of a study of vestibular reflex measurements in normal subjects and preliminary results in abnormal subjects are presented in this report. Statistical methods were used to define the range of normal responses, and determine age related changes in function.

  12. Bronchial abnormalities found in a consecutive series of 40 brachycephalic dogs.

    PubMed

    De Lorenzi, Davide; Bertoncello, Diana; Drigo, Michele

    2009-10-01

    To detect abnormalities of the lower respiratory tract (trachea, principal bronchi, and lobar bronchi) in brachycephalic dogs by use of endoscopy, evaluate the correlation between laryngeal collapse and bronchial abnormalities, and determine whether dogs with bronchial abnormalities have a less favorable postsurgical long-term outcome following correction of brachycephalic syndrome. Prospective case series study. 40 client-owned brachycephalic dogs with stertorous breathing and clinical signs of respiratory distress. Brachycephalic dogs anesthetized for pharyngoscopy and laryngoscopy between January 2007 and June 2008 underwent flexible bronchoscopy for systematic evaluation of the principal and lobar bronchi. For dogs that underwent surgical correction of any component of brachycephalic syndrome, owners rated surgical outcome during a follow-up telephone survey. Correlation between laryngeal collapse and bronchial abnormalities and association between bronchial abnormalities and long-term outcome were assessed. Pugs (n = 20), English Bulldogs (13), and French Bulldogs (7) were affected. A fixed bronchial collapse was recognized in 35 of 40 dogs with a total of 94 bronchial stenoses. Abnormalities were irregularly distributed between hemithoraces; 15 of 94 bronchial abnormalities were detected in the right bronchial system, and 79 of 94 were detected in the left. The left cranial bronchus was the most commonly affected structure, and Pugs were the most severely affected breed. Laryngeal collapse was significantly correlated with severe bronchial collapse; no significant correlation was found between severity of bronchial abnormalities and postsurgical outcome. Bronchial collapse was a common finding in brachycephalic dogs, and long-term postsurgical outcome was not affected by bronchial stenosis.

  13. Coronary vasomotor abnormalities in insulin-resistant individuals.

    PubMed

    Quiñones, Manuel J; Hernandez-Pampaloni, Miguel; Schelbert, Heinrich; Bulnes-Enriquez, Isabel; Jimenez, Xochitl; Hernandez, Gustavo; De La Rosa, Roxana; Chon, Yun; Yang, Huiying; Nicholas, Susanne B; Modilevsky, Tamara; Yu, Katherine; Van Herle, Katja; Castellani, Lawrence W; Elashoff, Robert; Hsueh, Willa A

    2004-05-04

    Insulin resistance is a metabolic spectrum that progresses from hyperinsulinemia to the metabolic syndrome, impaired glucose tolerance, and finally type 2 diabetes mellitus. It is unclear when vascular abnormalities begin in this spectrum of metabolic effects. To evaluate the association of insulin resistance with the presence and reversibility of coronary vasomotor abnormalities in young adults at low cardiovascular risk. Cross-sectional study followed by prospective, open-label treatment study. University hospital. 50 insulin-resistant and 22 insulin-sensitive, age-matched Mexican-American participants without glucose intolerance or traditional risk factors for or evidence of coronary artery disease. 3 months of thiazolidinedione therapy for 25 insulin-resistant patients. Glucose infusion rate in response to insulin infusion was used to define insulin resistance (glucose infusion rate < or = 4.00 mg/kg of body weight per minute [range, 0.90 to 3.96 mg/kg per minute]) and insulin sensitivity (glucose infusion rate > or = 7.50 mg/kg per minute [range, 7.52 to 13.92 mg/kg per minute]). Myocardial blood flow was measured by using positron emission tomography at rest, during cold pressor test (largely endothelium-dependent), and after dipyridamole administration (largely vascular smooth muscle-dependent). Myocardial blood flow responses to dipyridamole were similar in the insulin-sensitive and insulin-resistant groups. However, myocardial blood flow response to cold pressor test increased by 47.6% from resting values in insulin-sensitive patients and by 14.4% in insulin-resistant patients. During thiazolidinedione therapy in a subgroup of insulin-resistant patients, insulin sensitivity improved, fasting plasma insulin levels decreased, and myocardial blood flow responses to cold pressor test normalized. The study was not randomized, and it included only 1 ethnic group. Insulin-resistant patients who do not have hypercholesterolemia or hypertension and do not smoke

  14. Perceived functional impact of abnormal facial appearance.

    PubMed

    Rankin, Marlene; Borah, Gregory L

    2003-06-01

    Functional facial deformities are usually described as those that impair respiration, eating, hearing, or speech. Yet facial scars and cutaneous deformities have a significant negative effect on social functionality that has been poorly documented in the scientific literature. Insurance companies are declining payments for reconstructive surgical procedures for facial deformities caused by congenital disabilities and after cancer or trauma operations that do not affect mechanical facial activity. The purpose of this study was to establish a large, sample-based evaluation of the perceived social functioning, interpersonal characteristics, and employability indices for a range of facial appearances (normal and abnormal). Adult volunteer evaluators (n = 210) provided their subjective perceptions based on facial physical appearance, and an analysis of the consequences of facial deformity on parameters of preferential treatment was performed. A two-group comparative research design rated the differences among 10 examples of digitally altered facial photographs of actual patients among various age and ethnic groups with "normal" and "abnormal" congenital deformities or posttrauma scars. Photographs of adult patients with observable congenital and posttraumatic deformities (abnormal) were digitally retouched to eliminate the stigmatic defects (normal). The normal and abnormal photographs of identical patients were evaluated by the large sample study group on nine parameters of social functioning, such as honesty, employability, attractiveness, and effectiveness, using a visual analogue rating scale. Patients with abnormal facial characteristics were rated as significantly less honest (p = 0.007), less employable (p = 0.001), less trustworthy (p = 0.01), less optimistic (p = 0.001), less effective (p = 0.02), less capable (p = 0.002), less intelligent (p = 0.03), less popular (p = 0.001), and less attractive (p = 0.001) than were the same patients with normal facial

  15. The anatomy and development of normal and abnormal coronary arteries.

    PubMed

    Spicer, Diane E; Henderson, Deborah J; Chaudhry, Bill; Mohun, Timothy J; Anderson, Robert H

    2015-12-01

    At present, there is significant interest in the morphology of the coronary arteries, not least due to the increasingly well-recognised association between anomalous origin of the arteries and sudden cardiac death. Much has also been learnt over the last decade regarding the embryology of the arteries. In this review, therefore, we provide a brief introduction into the recent findings regarding their development. In particular, we emphasise that new evidence, derived using the developing murine heart, points to the arterial stems growing out from the adjacent sinuses of the aortic root, rather than the arteries growing in, as is currently assumed. As we show, the concept of outgrowth provides an excellent explanation for several of the abnormal arrangements encountered in the clinical setting. Before summarising these abnormal features, we draw attention to the need to describe the heart in an attitudinally appropriate manner, following the basic rule of human anatomy, rather than describing the cardiac components with the heart in the "Valentine" orientation. We then show how the major abnormalities involving the coronary arteries in humans can be summarised in terms of abnormal origin from the pulmonary circulation, abnormal aortic origin, or fistulous communications between the coronary arteries and the cardiac cavities. In the case of abnormal aortic origin, we highlight those malformations known to be associated with sudden cardiac death.

  16. Thalamic input to auditory cortex is locally heterogeneous but globally tonotopic

    PubMed Central

    Vasquez-Lopez, Sebastian A; Weissenberger, Yves; Lohse, Michael; Keating, Peter; King, Andrew J

    2017-01-01

    Topographic representation of the receptor surface is a fundamental feature of sensory cortical organization. This is imparted by the thalamus, which relays information from the periphery to the cortex. To better understand the rules governing thalamocortical connectivity and the origin of cortical maps, we used in vivo two-photon calcium imaging to characterize the properties of thalamic axons innervating different layers of mouse auditory cortex. Although tonotopically organized at a global level, we found that the frequency selectivity of individual thalamocortical axons is surprisingly heterogeneous, even in layers 3b/4 of the primary cortical areas, where the thalamic input is dominated by the lemniscal projection. We also show that thalamocortical input to layer 1 includes collaterals from axons innervating layers 3b/4 and is largely in register with the main input targeting those layers. Such locally varied thalamocortical projections may be useful in enabling rapid contextual modulation of cortical frequency representations. PMID:28891466

  17. The relationship of abnormal foot pronation to hallux abducto valgus--a pilot study.

    PubMed

    Ross, F D

    1986-08-01

    Abnormal foot mechanics is the most common cause of hallux abducto valgus. To date no quantitative data regarding the relationship between abnormal foot mechanics and the degree of hallux abducto valgus has been presented. An outline of the abnormal foot mechanics responsible for hallux abducto valgus is described along with a technique for measuring the extent of abnormal function. A common intrinsic abnormality responsible for hallux abducto valgus is described along with its diagnosis and orthotic treatment.

  18. Prior MDMA (Ecstasy) use is associated with increased basal ganglia–thalamocortical circuit activation during motor task performance in humans: An fMRI study

    PubMed Central

    Karageorgiou, John; Dietrich, Mary S.; Charboneau, Evonne J.; Woodward, Neil D.; Blackford, Jennifer U.; Salomon, Ronald M.; Cowan, Ronald L.

    2009-01-01

    MDMA (3,4-methylenedioxymethamphetamine; Ecstasy) is a popular recreational drug that produces long-lasting serotonin (5-HT) neurotoxicity consisting of reductions in markers for 5-HT axons. 5-HT innervates cortical and subcortical brain regions mediating motor function, predicting that MDMA users will have altered motor system neurophysiology. We used functional magnetic resonance imaging (fMRI) to assay motor task performance-associated brain activation changes in MDMA and non-MDMA users. 24 subjects (14 MDMA users and 10 controls) performed an event-related motor tapping task (1, 2 or 4 taps) during fMRI at 3 T. Motor regions of interest were used to measure percent signal change (PSC) and percent activated voxels (PAV) in bilateral motor cortex, sensory cortex, supplementary motor area (SMA), caudate, putamen, pallidum and thalamus. We used SPM5 to measure brain activation via three methods: T-maps, PSC and PAV. There was no statistically significant difference in reaction time between the two groups. For the Tap 4 condition, MDMA users had more activation than controls in the right SMA for T-score (p = 0.02), PSC (p = 0.04) and PAV (p = 0.03). Lifetime episodes of MDMA use were positively correlated with PSC for the Tap 4 condition on the right for putamen and pallidum; with PAV in the right motor and sensory cortex and bilateral thalamus. In conclusion, we found a group difference in the right SMA and positive dose–response association between lifetime exposure to MDMA and signal magnitude and extent in several brain regions. This evidence is consistent with MDMA-induced alterations in basal ganglia–thalamocortical circuit neurophysiology and is potentially secondary to neurotoxic effects on 5-HT signaling. Further studies examining behavioral correlates and the specific neurophysiological basis of the observed findings are warranted. PMID:19264142

  19. Prevalence and consequences of chromosomal abnormalities in Canadian commercial swine herds.

    PubMed

    Quach, Anh T; Revay, Tamas; Villagomez, Daniel A F; Macedo, Mariana P; Sullivan, Alison; Maignel, Laurence; Wyss, Stefanie; Sullivan, Brian; King, W Allan

    2016-09-12

    Structural chromosome abnormalities are well known as factors that reduce fertility rate in domestic pigs. According to large-scale national cytogenetic screening programs that are implemented in France, it is estimated that new chromosome abnormalities occur at a rate of 0.5 % in fertility-unproven boars. This work aimed at estimating the prevalence and consequences of chromosome abnormalities in commercial swine operations in Canada. We found pig carriers at a frequency of 1.64 % (12 out of 732 boars). Carrier pigs consistently showed lower fertility values. The total number of piglets born for litters from carrier boars was between 4 and 46 % lower than the herd average. Similarly, carrier boars produced litters with a total number of piglets born alive that was between 6 and 28 % lower than the herd average. A total of 12 new structural chromosome abnormalities were identified. Reproductive performance is significantly reduced in sires with chromosome abnormalities. The incidence of such abnormal sires appears relatively high in populations without routine cytogenetic screening such as observed for Canada in this study. Systematic cytogenetic screening of potential breeding boars would minimise the risk of carriers of chromosome aberrations entering artificial insemination centres. This would avoid the large negative effects on productivity for the commercial sow herds and reduce the risk of transmitting abnormalities to future generations in nucleus farms.

  20. Enhanced visualization of abnormalities in digital-mammographic images

    NASA Astrophysics Data System (ADS)

    Young, Susan S.; Moore, William E.

    2002-05-01

    This paper describes two new presentation methods that are intended to improve the ability of radiologists to visualize abnormalities in mammograms by enhancing the appearance of the breast parenchyma pattern relative to the fatty-tissue surroundings. The first method, referred to as mountain- view, is obtained via multiscale edge decomposition through filter banks. The image is displayed in a multiscale edge domain that causes the image to have a topographic-like appearance. The second method displays the image in the intensity domain and is referred to as contrast-enhancement presentation. The input image is first passed through a decomposition filter bank to produce a filtered output (Id). The image at the lowest resolution is processed using a LUT (look-up table) to produce a tone scaled image (I'). The LUT is designed to optimally map the code value range corresponding to the parenchyma pattern in the mammographic image into the dynamic range of the output medium. The algorithm uses a contrast weight control mechanism to produce the desired weight factors to enhance the edge information corresponding to the parenchyma pattern. The output image is formed using a reconstruction filter bank through I' and enhanced Id.

  1. Dynamic baseline detection method for power data network service

    NASA Astrophysics Data System (ADS)

    Chen, Wei

    2017-08-01

    This paper proposes a dynamic baseline Traffic detection Method which is based on the historical traffic data for the Power data network. The method uses Cisco's NetFlow acquisition tool to collect the original historical traffic data from network element at fixed intervals. This method uses three dimensions information including the communication port, time, traffic (number of bytes or number of packets) t. By filtering, removing the deviation value, calculating the dynamic baseline value, comparing the actual value with the baseline value, the method can detect whether the current network traffic is abnormal.

  2. Normally Expected Aberrations in the 8-hour Dynamic EKG

    NASA Technical Reports Server (NTRS)

    Fleck, R. L.; Arnoldi, L. B.; Townsend, J. C.; Tonesk, X.

    1970-01-01

    The establishment of norms for interpreting long term dynamic electrocardiograms is attempted by correlating a completely disease symptom and cardiac risk factor free sample with a non-pure sample in the direction of normality on various variables. Out of a population of 362 subjects exposed to dynamic electrocardiogram testing, a discrimination between normals and abnormals in terms of traditional risk factors was observed. The two groups differed significantly on the following variables: cholesterol, smoking, systolic blood pressure, white blood count, fasting blood sugar, uric acid, resting EKG, year of birth, and coronary insufficiency.

  3. Abnormal stress echocardiography findings in cardiac amyloidosis.

    PubMed

    Ong, Kevin C; Askew, J Wells; Dispenzieri, Angela; Maleszewski, Joseph J; Klarich, Kyle W; Anavekar, Nandan S; Mulvagh, Sharon L; Grogan, Martha

    2016-06-01

    Cardiac involvement in immunoglobulin light chain (amyloid light chain, AL) amyloidosis is characterized by myocardial interstitial deposition but can also cause obstructive deposits in the coronary microvasculature. We retrospectively identified 20 patients who underwent stress echocardiography within 1 year prior to the histologic diagnosis of AL amyloidosis. Only patients with cardiac amyloidosis and no known obstructive coronary disease were included. Stress echocardiograms (13 exercise; 7 dobutamine) were performed for evaluation of dyspnea and/or chest pain. Stress-induced wall motion abnormalities (WMAs) occurred in 11 patients (55%), 4 of whom had normal left ventricular wall thickness. Coronary angiogram was performed in 9 of 11 patients and demonstrated no or mild epicardial coronary artery disease. Seven (54%) patients had an abnormal exercise blood pressure which occurred with similar likelihood between those with and without stress-induced WMAs. Stress-induced WMAs and abnormal exercise blood pressure may occur in patients with cardiac AL amyloidosis despite the absence of significant epicardial coronary artery disease. This finding should raise the possibility of cardiac amyloidosis even in the absence of significant myocardial thickening.

  4. Migraine patients consistently show abnormal vestibular bedside tests.

    PubMed

    Maranhão, Eliana Teixeira; Maranhão-Filho, Péricles; Luiz, Ronir Raggio; Vincent, Maurice Borges

    2016-01-01

    Migraine and vertigo are common disorders, with lifetime prevalences of 16% and 7% respectively, and co-morbidity around 3.2%. Vestibular syndromes and dizziness occur more frequently in migraine patients. We investigated bedside clinical signs indicative of vestibular dysfunction in migraineurs. To test the hypothesis that vestibulo-ocular reflex, vestibulo-spinal reflex and fall risk (FR) responses as measured by 14 bedside tests are abnormal in migraineurs without vertigo, as compared with controls. Cross-sectional study including sixty individuals - thirty migraineurs, 25 women, 19-60 y-o; and 30 gender/age healthy paired controls. Migraineurs showed a tendency to perform worse in almost all tests, albeit only the Romberg tandem test was statistically different from controls. A combination of four abnormal tests better discriminated the two groups (93.3% specificity). Migraine patients consistently showed abnormal vestibular bedside tests when compared with controls.

  5. Freud Was Right. . . about the Origins of Abnormal Behavior

    ERIC Educational Resources Information Center

    Muris, Peter

    2006-01-01

    Freud's psychodynamic theory is predominantly based on case histories of patients who displayed abnormal behavior. From a scientific point of view, Freud's analyses of these cases are unacceptable because the key concepts of his theory cannot be tested empirically. However, in one respect, Freud was totally right: most forms of abnormal behavior…

  6. Impact of the dynamic and static component of the sport practised for electrocardiogram analysis in screening athletes.

    PubMed

    Maillot, N; Guenancia, C; Yameogo, N V; Gudjoncik, A; Garnier, F; Lorgis, L; Chagué, F; Cottin, Y

    2018-02-01

    To interpret the electrocardiogram (ECG) of athletes, the recommendations of the ESC and the Seattle criteria define type 1 peculiarities, those induced by training, and type 2, those not induced by training, to rule out cardiomyopathy. The specificity of the screening was improved by Sheikh who defined "Refined Criteria," which includes a group of intermediate peculiarities. The aim of our study was to investigate the influence of static and dynamic components on the prevalence of different types of abnormalities. The ECGs of 1030 athletes performed during preparticipation screening were interpreted using these three classifications. Our work revealed 62/16%, 69/13%, and 71/7% of type 1 peculiarities and type 2 abnormalities for the ESC, Seattle, and Refined Criteria algorithms, respectively(P<.001). For type 2 abnormalities, three independent factors were found for the ESC and Seattle criteria: age, Afro-Caribbean origin, and the dynamic component with, for the latter, an OR[95% CI] of 2.35[1.28-4.33] (P=.006) and 1.90[1.03-3.51] (P=.041), respectively. In contrast, only the Afro-Caribbean origin was associated with type 2 abnormalities using the Refined Criteria: OR[95% CI] 2.67[1.60-4.46] (P<.0001). The Refined Criteria classified more athletes in the type 1 category and fewer in the type 2 category compared with the ESC and Seattle algorithms. Contrary to previous studies, a high dynamic component was not associated with type 2 abnormalities when the Refined Criteria were used; only the Afro-Caribbean origin remained associated. Further research is necessary to better understand adaptations with regard to duration and thus improve the modern criteria for ECG screening in athletes. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Targeting Histone Abnormality in Triple Negative Breast Cancer

    DTIC Science & Technology

    2015-08-01

    Casero RA, Davidson NE. Molecular mechanisms of polyamine analogues in cancer cells. Anti - Cancer Drugs, 16(3): 229-241, 2005. PMID: 15711175 18 3...1 AWARD NUMBER: W81XWH-14-1-0237 TITLE: Targeting Histone Abnormality in Triple-Negative Breast Cancer PRINCIPAL INVESTIGATOR: Yi...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Histone Abnormality in Triple-Negative Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0237 5c

  8. Esophageal motility abnormalities in gastroesophageal reflux disease

    PubMed Central

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-01-01

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett’s esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted. PMID:24868489

  9. Esophageal motility abnormalities in gastroesophageal reflux disease.

    PubMed

    Martinucci, Irene; de Bortoli, Nicola; Giacchino, Maria; Bodini, Giorgia; Marabotto, Elisa; Marchi, Santino; Savarino, Vincenzo; Savarino, Edoardo

    2014-05-06

    Esophageal motility abnormalities are among the main factors implicated in the pathogenesis of gastroesophageal reflux disease. The recent introduction in clinical and research practice of novel esophageal testing has markedly improved our understanding of the mechanisms contributing to the development of gastroesophageal reflux disease, allowing a better management of patients with this disorder. In this context, the present article intends to provide an overview of the current literature about esophageal motility dysfunctions in patients with gastroesophageal reflux disease. Esophageal manometry, by recording intraluminal pressure, represents the gold standard to diagnose esophageal motility abnormalities. In particular, using novel techniques, such as high resolution manometry with or without concurrent intraluminal impedance monitoring, transient lower esophageal sphincter (LES) relaxations, hypotensive LES, ineffective esophageal peristalsis and bolus transit abnormalities have been better defined and strongly implicated in gastroesophageal reflux disease development. Overall, recent findings suggest that esophageal motility abnormalities are increasingly prevalent with increasing severity of reflux disease, from non-erosive reflux disease to erosive reflux disease and Barrett's esophagus. Characterizing esophageal dysmotility among different subgroups of patients with reflux disease may represent a fundamental approach to properly diagnose these patients and, thus, to set up the best therapeutic management. Currently, surgery represents the only reliable way to restore the esophagogastric junction integrity and to reduce transient LES relaxations that are considered to be the predominant mechanism by which gastric contents can enter the esophagus. On that ground, more in depth future studies assessing the pathogenetic role of dysmotility in patients with reflux disease are warranted.

  10. Abnormal fronto-limbic engagement in incarcerated stimulant users during moral processing.

    PubMed

    Fede, Samantha J; Harenski, Carla L; Schaich Borg, Jana; Sinnott-Armstrong, Walter; Rao, Vikram; Caldwell, Brendan M; Nyalakanti, Prashanth K; Koenigs, Michael R; Decety, Jean; Calhoun, Vince D; Kiehl, Kent A

    2016-09-01

    Stimulant use is a significant and prevalent problem, particularly in criminal populations. Previous studies found that cocaine and methamphetamine use is related to impairment in identifying emotions and empathy. Stimulant users also have abnormal neural structure and function of the ventromedial prefrontal cortex (vmPFC), amygdala, and anterior (ACC) and posterior cingulate (PCC), regions implicated in moral decision-making. However, no research has studied the neural correlates of stimulant use and explicit moral processing in an incarcerated population. Here, we examine how stimulant use affects sociomoral processing that might contribute to antisocial behavior. We predicted that vmPFC, amygdala, PCC, and ACC would show abnormal neural response during a moral processing task in incarcerated methamphetamine and cocaine users. Incarcerated adult males (N = 211) were scanned with a mobile MRI system while completing a moral decision-making task. Lifetime drug use was assessed. Neural responses during moral processing were compared between users and non-users. The relationship between duration of use and neural function was also examined. Incarcerated stimulant users showed less amygdala engagement than non-users during moral processing. Duration of stimulant use was negatively associated with activity in ACC and positively associated with vmPFC response during moral processing. These results suggest a dynamic pattern of fronto-limbic moral processing related to stimulant use with deficits in both central motive and cognitive integration elements of biological moral processes theory. This increases our understanding of how drug use relates to moral processing in the brain in an ultra-high-risk population.

  11. Abnormal cardiovascular response to exercise in hypertension: contribution of neural factors.

    PubMed

    Mitchell, Jere H

    2017-06-01

    During both dynamic (e.g., endurance) and static (e.g., strength) exercise there are exaggerated cardiovascular responses in hypertension. This includes greater increases in blood pressure, heart rate, and efferent sympathetic nerve activity than in normal controls. Two of the known neural factors that contribute to this abnormal cardiovascular response are the exercise pressor reflex (EPR) and functional sympatholysis. The EPR originates in contracting skeletal muscle and reflexly increases sympathetic efferent nerve activity to the heart and blood vessels as well as decreases parasympathetic efferent nerve activity to the heart. These changes in autonomic nerve activity cause an increase in blood pressure, heart rate, left ventricular contractility, and vasoconstriction in the arterial tree. However, arterial vessels in the contracting skeletal muscle have a markedly diminished vasoconstrictor response. The markedly diminished vasoconstriction in contracting skeletal muscle has been termed functional sympatholysis. It has been shown in hypertension that there is an enhanced EPR, including both its mechanoreflex and metaboreflex components, and an impaired functional sympatholysis. These conditions set up a positive feedback or vicious cycle situation that causes a progressively greater decrease in the blood flow to the exercising muscle. Thus these two neural mechanisms contribute significantly to the abnormal cardiovascular response to exercise in hypertension. In addition, exercise training in hypertension decreases the enhanced EPR, including both mechanoreflex and metaboreflex function, and improves the impaired functional sympatholysis. These two changes, caused by exercise training, improve the muscle blood flow to exercising muscle and cause a more normal cardiovascular response to exercise in hypertension. Copyright © 2017 the American Physiological Society.

  12. Abnormalities in amphibian populations inhabiting agroecosystems in Northeastern Buenos Aires Province, Argentina.

    PubMed

    Agostini, M G; Kacoliris, F; Demetrio, P; Natale, G S; Bonetto, C; Ronco, A E

    2013-05-27

    The occurrence of abnormalities in amphibians has been reported in many populations, and its increase could be related to environmental pollution and habitat degradation. We evaluated the type and prevalence of abnormalities in 5 amphibian populations from agroecosystems with different degrees of agricultural disturbance (cultivated and reference areas). We detected 9 types of abnormalities, of which the most frequent were those occurring in limbs. The observed prevalence of abnormality in assessed populations from cultivated and reference areas was as follows: Rhinella fernandezae (37.1 and 10.2%, respectively), Leptodactylus latrans adults (28.1 and 9.2%) and juveniles (32.9 and 15.3%), and Hypsiboas pulchellus (11.6 and 2.8%). Scinax granulatus populations did not show abnormalities. Pseudis minuta, which was only detected in the reference area, exhibited a prevalence of 13.3%. For R. fernandezae, L. latrans, and H. pulchellus, generalized linear mixed models showed that prevalence of abnormalities was significantly higher (p < 0.05) in cultivated than in reference areas. L. latrans juveniles were more vulnerable to abnormalities than adults (p < 0.05). The presence of abnormalities in some species inhabiting different agroecosystems suggests that environmental stress factors might be responsible for their occurrence. While we detected pesticides (endosulfan, cypermethrin, and chlorpyrifos) and lower dissolved oxygen levels in ponds of the cultivated area, no data are currently available on how other factors, such as injuries from predators and parasite infections, vary by land use. Further research will be necessary to evaluate possible causes of abnormalities detected in the present study mainly in the context of factor interactions.

  13. Pulmonary Gas Exchange Abnormalities in Mild Chronic Obstructive Pulmonary Disease. Implications for Dyspnea and Exercise Intolerance.

    PubMed

    Elbehairy, Amany F; Ciavaglia, Casey E; Webb, Katherine A; Guenette, Jordan A; Jensen, Dennis; Mourad, Sahar M; Neder, J Alberto; O'Donnell, Denis E

    2015-06-15

    Several studies in mild chronic obstructive pulmonary disease (COPD) have shown a higher than normal ventilatory equivalent for carbon dioxide ([Formula: see text]e/[Formula: see text]co2) during exercise. Our objective was to examine pulmonary gas exchange abnormalities and the mechanisms of high [Formula: see text]e/[Formula: see text]co2 in mild COPD and its impact on dyspnea and exercise intolerance. Twenty-two subjects (11 patients with GOLD [Global Initiative for Chronic Obstructive Lung Disease] grade 1B COPD, 11 age-matched healthy control subjects) undertook physiological testing and a symptom-limited incremental cycle exercise test with arterial blood gas collection. Patients (post-bronchodilator FEV1: 94 ± 10% predicted; mean ± SD) had evidence of peripheral airway dysfunction and reduced peak oxygen uptake compared with control subjects (80 ± 18 vs. 113 ± 24% predicted; P<0.05). Arterial blood gases were within the normal range and effective alveolar ventilation was not significantly different from control subjects throughout exercise. The alveolar-arterial O2 tension gradient was elevated at rest and throughout exercise in COPD (P<0.05). [Formula: see text]e/[Formula: see text]co2, dead space to tidal volume ratio (Vd/Vt), and arterial to end-tidal CO2 difference were all higher (P<0.05) in patients with COPD than in control subjects during exercise. In patients with COPD versus control subjects, there was significant dynamic hyperinflation and greater tidal volume constraints (P<0.05). Standardized dyspnea intensity ratings were also higher (P<0.05) in patients with COPD versus control subjects in association with higher ventilatory requirements. Within all subjects, Vd/Vt correlated with the [Formula: see text]e/[Formula: see text]co2 ratio during submaximal exercise (r=0.780, P<0.001). High Vd/Vt was the most consistent gas exchange abnormality in smokers with only mild spirometric abnormalities. Compensatory increases in minute

  14. Adenotonsillar hypertrophy as a risk factor of dentofacial abnormality in Korean children.

    PubMed

    Kim, Dong-Kyu; Rhee, Chae Seo; Yun, Pil-Young; Kim, Jeong-Whun

    2015-11-01

    No studies for the role of adenotonsillar hypertrophy in development of dentofacial abnormalities have been performed in Asian pediatric population. Thus, we aimed to investigate the relationship between adenotonsillar hypertrophy and dentofacial abnormalities in Korean children. The present study included consecutive children who visited a pediatric clinic for sleep-disordered breathing due to habitual mouth breathing, snoring or sleep apnea. Their palatine tonsils and adenoids were graded by oropharyngeal endoscopy and lateral cephalometry. Anterior open bite, posterior crossbite, and Angle's class malocclusions were evaluated for dentofacial abnormality. The receiver-operating characteristic curve analysis was used to identify age cutoffs to predict dentofacial abnormality. A total of 1,083 children were included. The presence of adenotonsillar hypertrophy was significantly correlated with the prevalence of dentofacial abnormality [adjusted odds ratio = 4.587, 95% CI (2.747-7.658)] after adjusting age, sex, body mass index, allergy, and Korean version of obstructive sleep apnea-18 score. The cutoff age associated with dentofacial abnormality was 5.5 years (sensitivity = 75.5%, specificity = 67%) in the children with adenotonsillar hypertrophy and 6.5 years (sensitivity = 70.6%, specificity = 57%) in those without adenotonsillar hypertrophy. In conclusion, adenotonsillar hypertrophy may be a risk factor for dentofacial abnormalities in Korean children and early surgical intervention could be considered with regards to dentofacial abnormality.

  15. Progress in Mathematical Modeling of Gastrointestinal Slow Wave Abnormalities

    PubMed Central

    Du, Peng; Calder, Stefan; Angeli, Timothy R.; Sathar, Shameer; Paskaranandavadivel, Niranchan; O'Grady, Gregory; Cheng, Leo K.

    2018-01-01

    Gastrointestinal (GI) motility is regulated in part by electrophysiological events called slow waves, which are generated by the interstitial cells of Cajal (ICC). Slow waves propagate by a process of “entrainment,” which occurs over a decreasing gradient of intrinsic frequencies in the antegrade direction across much of the GI tract. Abnormal initiation and conduction of slow waves have been demonstrated in, and linked to, a number of GI motility disorders. A range of mathematical models have been developed to study abnormal slow waves and applied to propose novel methods for non-invasive detection and therapy. This review provides a general outline of GI slow wave abnormalities and their recent classification using multi-electrode (high-resolution) mapping methods, with a particular emphasis on the spatial patterns of these abnormal activities. The recently-developed mathematical models are introduced in order of their biophysical scale from cellular to whole-organ levels. The modeling techniques, main findings from the simulations, and potential future directions arising from notable studies are discussed. PMID:29379448

  16. Chromosomal abnormalities, meiotic behavior and fertility in domestic animals.

    PubMed

    Villagómez, D A F; Pinton, A

    2008-01-01

    Since the advent of the surface microspreading technique for synaptonemal complex analysis, increasing interest in describing the synapsis patterns of chromosome abnormalities associated with fertility of domestic animals has been noticed during the past three decades. In spite of the number of scientific reports describing the occurrence of structural chromosome abnormalities, their meiotic behavior and gametic products, little is known in domestic animal species about the functional effects of such chromosome aberrations in the germ cell line of carriers. However, some interesting facts gained from recent and previous studies on the meiotic behavior of chromosome abnormalities of domestic animals permit us to discuss, in the frame of recent knowledge emerging from mouse and human investigations, the possible mechanism implicated in the well known association between meiotic disruption and chromosome pairing failure. New cytogenetic techniques, based on molecular and immunofluorescent analyses, are allowing a better description of meiotic processes, including gamete production. The present communication reviews the knowledge of the meiotic consequences of chromosome abnormalities in domestic animals. Copyright 2008 S. Karger AG, Basel.

  17. T wave abnormalities, high body mass index, current smoking and high lipoprotein (a) levels predict the development of major abnormal Q/QS patterns 20 years later. A population-based study

    PubMed Central

    Moller, Christina Strom; Byberg, Liisa; Sundstrom, Johan; Lind, Lars

    2006-01-01

    Background Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome. Methods Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later. Results At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern. Conclusion T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI. PMID:16519804

  18. Investigation of frog abnormalities on national wildlife refuges in the Northeast U.S.

    USGS Publications Warehouse

    Eaton-Poole, L.; Pinkney, A.E.; Green, D.E.; Sutherland, D.R.; Babbitt, K.J.; ,

    2003-01-01

    To address concerns about frog abnormalities, the U.S. Fish and Wildlife Service examined over 3,643 frogs and toads on National Wildlife Refuges (NWRs) in the Northeast U.S. The objectives were to: 1) determine if certain refuges had sites where abnormalities were frequently observed; 2) evaluate if the prevalence of abnormalities at a site was consistent within a season and among years; and 3) investigate possible causes. Sampling was conducted from 1999 through 2001. A complete sample from a site consisted of ???50 metamorphs of one species. The prevalence of abnormalities ranged from 0 to 15% and fluctuated within season and among years. The most common external abnormalities were truncated limbs, and missing limbs, feet, and digits. Frogs with duplication of limb segments were rare (6). Based on radiographical examinations of 89 abnormal frogs, 55 had abnormalities due to trauma, 22 due to malformations, and 12 could not be classified. Metacercariae of the trematode Ribeiroia were detected in substantial numbers in two species from Iroquois NWR, with one specimen having supernumerary hindlimbs. We recommend continued sampling and integrated, causal evaluations on NWRs where the prevalence of abnormalities exceeds 5% or where the types of abnormalities warrant further study.

  19. Environmentally toxicant exposures induced intragenerational transmission of liver abnormalities in mice

    PubMed Central

    Al-Griw, Mohamed A.; Treesh, Soad A.; Alghazeer, Rabia O.; Regeai, Sassia O.

    2017-01-01

    Environmental toxicants such as chemicals, heavy metals, and pesticides have been shown to promote transgenerational inheritance of abnormal phenotypes and/or diseases to multiple subsequent generations following parental and/or ancestral exposures. This study was designed to examine the potential transgenerational action of the environmental toxicant trichloroethane (TCE) on transmission of liver abnormality, and to elucidate the molecular etiology of hepatocyte cell damage. A total of thirty two healthy immature female albino mice were randomly divided into three equal groups as follows: a sham group, which did not receive any treatment; a vehicle group, which received corn oil alone, and TCE treated group (3 weeks, 100 μg/kg i.p., every 4th day). The F0 and F1 generation control and TCE populations were sacrificed at the age of four months, and various abnormalities histpathologically investigated. Cell death and oxidative stress indices were also measured. The present study provides experimental evidence for the inheritance of environmentally induced liver abnormalities in mice. The results of this study show that exposure to the TCE promoted adult onset liver abnormalities in F0 female mice as well as unexposed F1 generation offspring. It is the first study to report a transgenerational liver abnormalities in the F1 generation mice through maternal line prior to gestation. This finding was based on careful evaluation of liver histopathological abnormalities, apoptosis of hepatocytes, and measurements of oxidative stress biomarkers (lipid peroxidation, protein carbonylation, and nitric oxide) in control and TCE populations. There was an increase in liver histopathological abnormalities, cell death, and oxidative lipid damage in F0 and F1 hepatic tissues of TCE treated group. In conclusion, this study showed that the biological and health impacts of environmental toxicant TCE do not end in maternal adults, but are passed on to offspring generations. Hence

  20. Detection of Abnormal Events via Optical Flow Feature Analysis

    PubMed Central

    Wang, Tian; Snoussi, Hichem

    2015-01-01

    In this paper, a novel algorithm is proposed to detect abnormal events in video streams. The algorithm is based on the histogram of the optical flow orientation descriptor and the classification method. The details of the histogram of the optical flow orientation descriptor are illustrated for describing movement information of the global video frame or foreground frame. By combining one-class support vector machine and kernel principal component analysis methods, the abnormal events in the current frame can be detected after a learning period characterizing normal behaviors. The difference abnormal detection results are analyzed and explained. The proposed detection method is tested on benchmark datasets, then the experimental results show the effectiveness of the algorithm. PMID:25811227

  1. Abnormal laughter-like vocalisations replacing speech in primary progressive aphasia.

    PubMed

    Rohrer, Jonathan D; Warren, Jason D; Rossor, Martin N

    2009-09-15

    We describe ten patients with a clinical diagnosis of primary progressive aphasia (PPA) (pathologically confirmed in three cases) who developed abnormal laughter-like vocalisations in the context of progressive speech output impairment leading to mutism. Failure of speech output was accompanied by increasing frequency of the abnormal vocalisations until ultimately they constituted the patient's only extended utterance. The laughter-like vocalisations did not show contextual sensitivity but occurred as an automatic vocal output that replaced speech. Acoustic analysis of the vocalisations in two patients revealed abnormal motor features including variable note duration and inter-note interval, loss of temporal symmetry of laugh notes and loss of the normal decrescendo. Abnormal laughter-like vocalisations may be a hallmark of a subgroup in the PPA spectrum with impaired control and production of nonverbal vocal behaviour due to disruption of fronto-temporal networks mediating vocalisation.

  2. Expression profiling of mouse subplate reveals a dynamic gene network and disease association with autism and schizophrenia

    PubMed Central

    Hoerder-Suabedissen, Anna; Oeschger, Franziska M.; Krishnan, Michelle L.; Belgard, T. Grant; Wang, Wei Zhi; Lee, Sheena; Webber, Caleb; Petretto, Enrico; Edwards, A. David; Molnár, Zoltán

    2013-01-01

    The subplate zone is a highly dynamic transient sector of the developing cerebral cortex that contains some of the earliest generated neurons and the first functional synapses of the cerebral cortex. Subplate cells have important functions in early establishment and maturation of thalamocortical connections, as well as in the development of inhibitory cortical circuits in sensory areas. So far no role has been identified for cells in the subplate in the mature brain and disease association of the subplate-specific genes has not been analyzed systematically. Here we present gene expression evidence for distinct roles of the mouse subplate across development as well as unique molecular markers to extend the repertoire of subplate labels. Performing systematic comparisons between different ages (embryonic days 15 and 18, postnatal day 8, and adult), we reveal the dynamic and constant features of the markers labeling subplate cells during embryonic and early postnatal development and in the adult. This can be visualized using the online database of subplate gene expression at https://molnar.dpag.ox.ac.uk/subplate/. We also identify embryonic similarities in gene expression between the ventricular zones, intermediate zone, and subplate, and distinct postnatal similarities between subplate, layer 5, and layers 2/3. The genes expressed in a subplate-specific manner at some point during development show a statistically significant enrichment for association with autism spectrum disorders and schizophrenia. Our report emphasizes the importance of the study of transient features of the developing brain to better understand neurodevelopmental disorders. PMID:23401504

  3. 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.

  4. Gonadotrophin abnormalities in an infant with Lowe syndrome.

    PubMed

    Warner, Bronwen E; Inward, Carol D; Burren, Christine P

    2017-01-01

    This case, presenting with bilateral impalpable testes, illustrates the relevance of a broad differential disorders of sex development case management. It provides new insights on hypothalamic-pituitary-gonadal (HPG) axis and testicular function abnormalities in the multisystem disorder of Lowe syndrome. Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare disorder characterised by eye abnormalities, central nervous system involvement and proximal renal tubular acidosis. There are a handful of reports of pubertal delay, infertility and cryptorchidism in Lowe syndrome. Biochemistry aged 72 h: testosterone 6.4 nmol/L, LH <0.5 IU/L and FSH <0.5 IU/L. Gonadotropin-releasing hormone stimulation test identified significantly raised baseline LH = 45.4 IU/L (contrasts with earlier undetectable LH), with a 20% increase on stimulation, while baseline FSH = 4.3 IU/L with no increase on stimulation. Day 14 HCG stimulation test produced an acceptable 50% increase in testosterone. The constellation of further abnormalities suggested Lowe syndrome: hypotonia, bilateral cataracts (surgical extraction and intraocular lens implantation) and renal tubular acidosis (microscopic haematuria, hypercalciuria, proteinuria, generalised aminoaciduria, hypophosphataemia and metabolic acidosis). DNA sequencing identified de novo hemizygous frameshift mutation OCRL c.2409_2410delCT in exon 22. Interpretation of initial and repeat GnRH and HCG testing indicates the likelihood of testicular failure. Partial testicular descent occurred but left orchidopexy was required. Improving long-term gonadal function in Lowe syndrome assumes increased importance for current cohorts as advances in renal replacement therapy have greatly improved life expectancy. Noting HPG axis abnormalities in Lowe syndrome in infancy can identify cases requiring increased surveillance of pubertal progress for earlier detection and management. Clinical endocrine problems in Lowe syndrome has

  5. The Prevalence and Significance of Abnormal Vital Signs Prior to In-Hospital Cardiac Arrest

    PubMed Central

    Andersen, Lars W.; Kim, Won Young; Chase, Maureen; Berg, Katherine; Mortensen, Sharri J.; Moskowitz, Ari; Novack, Victor; Cocchi, Michael N.; Donnino, Michael W.

    2015-01-01

    Background Patients suffering in-hospital cardiac arrest often show signs of physiological deterioration before the event. The purpose of this study was to determine the prevalence of abnormal vital signs 1–4 hours before cardiac arrest, and to evaluate the association between these vital sign abnormalities and inhospital mortality. Methods We included adults from the Get With the Guidelines® - Resuscitation registry with an in-hospital cardiac arrest. We used two a priori definitions for vital signs: abnormal (heart rate (HR) ≤ 60 or ≥ 100 min−1, respiratory rate (RR) ≤ 10 or > 20 min−1 and systolic blood pressure (SBP) ≤ 90 mm Hg) and severely abnormal (HR ≤ 50 or ≥ 130 min−1, RR ≤ 8 or ≥ 30 min−1 and SBP ≤80 mm Hg). We evaluated the association between the number of abnormal vital signs and in-hospital mortality using a multivariable logistic regression model. Results 7,851 patients were included. Individual vital signs were associated with in-hospital mortality. The majority of patients (59.4%) had at least one abnormal vital sign 1–4 hours before the arrest and 13.4% had at least one severely abnormal sign. We found a step-wise increase in mortality with increasing number of abnormal vital signs within the abnormal (odds ratio (OR) 1.53 (CI: 1.42 – 1.64) and severely abnormal groups (OR 1.62 [CI: 1.38 – 1.90]). This remained in multivariable analysis (abnormal: OR 1.38 [CI: 1.28 – 1.48], and severely abnormal: OR 1.40 [CI: 1.18 – 1.65]). Conclusion Abnormal vital signs are prevalent 1–4 hours before in-hospital cardiac arrest on hospital wards. Inhospital mortality increases with increasing number of pre-arrest abnormal vital signs as well as increased severity of vital sign derangements. PMID:26362486

  6. Topiramate for Abnormal Eating Behaviour in Frontotemporal Dementia

    PubMed Central

    Singam, Colin; Walterfang, Mark; Mocellin, Ramon; Evans, Andrew; Velakoulis, Dennis

    2013-01-01

    Topiramate is a sulfamate-substituted monosaccharide anticonvulsant that is associated with anorexia and weight loss and has been used to treat binge eating disorder and bulimia nervosa. This report describes a man with frontotemporal dementia, behavioural variant, associated with abnormal eating behaviour which appeared to respond to topiramate. We review the physiological basis of abnormal eating behaviour in frontotemporal dementia and explore possible mechanisms of action by which topiramate may modify eating behaviour in this condition. PMID:23548883

  7. Abnormality, rationality, and sanity.

    PubMed

    Hertwig, Ralph; Volz, Kirsten G

    2013-11-01

    A growing body of studies suggests that neurological and mental abnormalities foster conformity to norms of rationality that are widely endorsed in economics and psychology, whereas normality stands in the way of rationality thus defined. Here, we outline the main findings of these studies, discuss their implications for experimental design, and consider how 'sane' some benchmarks of rationality really are. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Abnormal lung function at preschool age asthma in adolescence?

    PubMed

    Lajunen, Katariina; Kalliola, Satu; Kotaniemi-Syrjänen, Anne; Sarna, Seppo; Malmberg, L Pekka; Pelkonen, Anna S; Mäkelä, Mika J

    2018-05-01

    Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Risk factors for early cytologic abnormalities after loop electrosurgical excision procedure.

    PubMed

    Dietrich, Charles S; Yancey, Michael K; Miyazawa, Kunio; Williams, David L; Farley, John

    2002-02-01

    To evaluate risk factors for early cytologic abnormalities and recurrent cervical dysplasia after loop electrosurgical excision procedure (LEEP). A retrospective analysis was performed of all pathology records for LEEPs performed at our institution from January 1996 through July 1998. Follow-up cytology from 2 through 12 months after LEEP was reviewed. Patients with abnormal cytology were referred for further colposcopic evaluation. Statistical analysis using chi2 test for trend, proportional hazards model test, Fisher exact tests, and life table analysis were performed to identify risk factors for early cytologic abnormalities after LEEP and to determine relative risk of recurrent dysplasia. A total of 298 women underwent LEEP during the study period, and 29% of these had cytologic abnormalities after LEEP. Grade of dysplasia, ectocervical marginal status, endocervical marginal status, and glandular involvement with dysplasia were not found to be independent risk factors for early cytologic abnormalities. However, when risk factors were analyzed cumulatively, the abnormal cytology rate increased from 24% with no risk factors to 67% with three risk factors present (P =.037). Of patients with abnormal cytology after LEEP, 40% developed subsequent dysplasia, and the mean time to diagnosis was approximately 6 months. The relative risk of subsequent dysplasia ranged from a 20% increase to twice the risk if post-LEEP cytology was low-grade squamous intraepithelial lesion or high-grade squamous intraepithelial lesion, respectively. Based on these results, consideration should be given for early colposcopic examination of patients who have evidence of marginal involvement or endocervical glandular involvement with dysplasia. These patients are at increased risk for abnormal cytology and recurrent dysplasia. This initial visit should occur at 6 months, as the mean time to recurrence of dysplasia was 6.5 months.

  10. Binocular combination in abnormal binocular vision

    PubMed Central

    Ding, Jian; Klein, Stanley A.; Levi, Dennis M.

    2013-01-01

    We investigated suprathreshold binocular combination in humans with abnormal binocular visual experience early in life. In the first experiment we presented the two eyes with equal but opposite phase shifted sine waves and measured the perceived phase of the cyclopean sine wave. Normal observers have balanced vision between the two eyes when the two eyes' images have equal contrast (i.e., both eyes contribute equally to the perceived image and perceived phase = 0°). However, in observers with strabismus and/or amblyopia, balanced vision requires a higher contrast image in the nondominant eye (NDE) than the dominant eye (DE). This asymmetry between the two eyes is larger than predicted from the contrast sensitivities or monocular perceived contrast of the two eyes and is dependent on contrast and spatial frequency: more asymmetric with higher contrast and/or spatial frequency. Our results also revealed a surprising NDE-to-DE enhancement in some of our abnormal observers. This enhancement is not evident in normal vision because it is normally masked by interocular suppression. However, in these abnormal observers the NDE-to-DE suppression was weak or absent. In the second experiment, we used the identical stimuli to measure the perceived contrast of a cyclopean grating by matching the binocular combined contrast to a standard contrast presented to the DE. These measures provide strong constraints for model fitting. We found asymmetric interocular interactions in binocular contrast perception, which was dependent on both contrast and spatial frequency in the same way as in phase perception. By introducing asymmetric parameters to the modified Ding-Sperling model including interocular contrast gain enhancement, we succeeded in accounting for both binocular combined phase and contrast simultaneously. Adding binocular contrast gain control to the modified Ding-Sperling model enabled us to predict the results of dichoptic and binocular contrast discrimination experiments

  11. Binocular combination in abnormal binocular vision.

    PubMed

    Ding, Jian; Klein, Stanley A; Levi, Dennis M

    2013-02-08

    We investigated suprathreshold binocular combination in humans with abnormal binocular visual experience early in life. In the first experiment we presented the two eyes with equal but opposite phase shifted sine waves and measured the perceived phase of the cyclopean sine wave. Normal observers have balanced vision between the two eyes when the two eyes' images have equal contrast (i.e., both eyes contribute equally to the perceived image and perceived phase = 0°). However, in observers with strabismus and/or amblyopia, balanced vision requires a higher contrast image in the nondominant eye (NDE) than the dominant eye (DE). This asymmetry between the two eyes is larger than predicted from the contrast sensitivities or monocular perceived contrast of the two eyes and is dependent on contrast and spatial frequency: more asymmetric with higher contrast and/or spatial frequency. Our results also revealed a surprising NDE-to-DE enhancement in some of our abnormal observers. This enhancement is not evident in normal vision because it is normally masked by interocular suppression. However, in these abnormal observers the NDE-to-DE suppression was weak or absent. In the second experiment, we used the identical stimuli to measure the perceived contrast of a cyclopean grating by matching the binocular combined contrast to a standard contrast presented to the DE. These measures provide strong constraints for model fitting. We found asymmetric interocular interactions in binocular contrast perception, which was dependent on both contrast and spatial frequency in the same way as in phase perception. By introducing asymmetric parameters to the modified Ding-Sperling model including interocular contrast gain enhancement, we succeeded in accounting for both binocular combined phase and contrast simultaneously. Adding binocular contrast gain control to the modified Ding-Sperling model enabled us to predict the results of dichoptic and binocular contrast discrimination experiments

  12. 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.

  13. Chromosomal abnormalities in a psychiatric population

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

    Lewis, K.E.; Lubetsky, M.J.; Wenger, S.L.

    Over a 3.5 year period of time, 345 patients hospitalized for psychiatric problems were evaluated cytogenetically. The patient population included 76% males and 94% children with a mean age of 12 years. The criteria for testing was an undiagnosed etiology for mental retardation and/or autism. Cytogenetic studies identified 11, or 3%, with abnormal karyotypes, including 4 fragile X positive individuals (2 males, 2 females), and 8 with chromosomal aneuploidy, rearrangements, or deletions. While individuals with chromosomal abnormalities do not demonstrate specific behavioral, psychiatric, or developmental problems relative to other psychiatric patients, our results demonstrate the need for an increased awarenessmore » to order chromosomal analysis and fragile X testing in those individuals who have combinations of behavioral/psychiatric, learning, communication, or cognitive disturbance. 5 refs., 1 fig., 2 tabs.« less

  14. Reduced laser-evoked potential habituation detects abnormal central pain processing in painful radiculopathy patients.

    PubMed

    Hüllemann, P; von der Brelie, C; Manthey, G; Düsterhöft, J; Helmers, A K; Synowitz, M; Baron, R

    2017-05-01

    Repetitive painful laser stimuli lead to physiological laser-evoked potential (LEP) habituation, measurable by a decrement of the N2/P2 amplitude. The time course of LEP-habituation is reduced in the capsaicin model for peripheral and central sensitization and in patients with migraine and fibromyalgia. In the present investigation, we aimed to assess the time course of LEP-habituation in a neuropathic pain syndrome, i.e. painful radiculopathy. At the side of radiating pain, four blocks of 25 painful laser stimuli each were applied to the ventral thigh at the L3 dermatome in 27 patients with painful radiculopathy. Inclusion criteria were (1) at least one neurological finding of radiculopathy, (2) low back pain with radiation into the foot and (3) a positive one-sided compression of the L5 and/or S1 root in the MRI. The time course of LEP-habituation was compared to 20 healthy height and age matched controls. Signs of peripheral (heat hyperalgesia) and central sensitization (dynamic mechanical allodynia and hyperalgesia) at the affected L5 or S1 dermatome were assessed with quantitative sensory testing. Painful radiculopathy patients showed decreased LEP-habituation compared to controls. Patients with signs of central sensitization showed a more prominent LEP-habituation decrease within the radiculopathy patient group. Laser-evoked potential habituation is reduced in painful radiculopathy patients, which indicates an abnormal central pain processing. Central sensitization seems to be a major contributor to abnormal LEP habituation. The LEP habituation paradigm might be useful as a clinical tool to assess central pain processing alterations in nociceptive and neuropathic pain conditions. Abnormal central pain processing in neuropathic pain conditions may be revealed with the laser-evoked potential habituation paradigm. In painful radiculopathy patients, LEP-habituation is reduced compared to healthy controls. © 2017 European Pain Federation - EFIC®.

  15. Abnormal laughter-like vocalisations replacing speech in primary progressive aphasia

    PubMed Central

    Rohrer, Jonathan D.; Warren, Jason D.; Rossor, Martin N.

    2009-01-01

    We describe ten patients with a clinical diagnosis of primary progressive aphasia (PPA) (pathologically confirmed in three cases) who developed abnormal laughter-like vocalisations in the context of progressive speech output impairment leading to mutism. Failure of speech output was accompanied by increasing frequency of the abnormal vocalisations until ultimately they constituted the patient's only extended utterance. The laughter-like vocalisations did not show contextual sensitivity but occurred as an automatic vocal output that replaced speech. Acoustic analysis of the vocalisations in two patients revealed abnormal motor features including variable note duration and inter-note interval, loss of temporal symmetry of laugh notes and loss of the normal decrescendo. Abnormal laughter-like vocalisations may be a hallmark of a subgroup in the PPA spectrum with impaired control and production of nonverbal vocal behaviour due to disruption of fronto-temporal networks mediating vocalisation. PMID:19435636

  16. Left globus pallidus abnormality in never-medicated patients with schizophrenia

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

    Early, T.S.; Reiman, E.M.; Raichle, M.E.

    1987-01-01

    Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5more » patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found.« less

  17. Abnormal mitochondrial respiration in failed human myocardium.

    PubMed

    Sharov, V G; Todor, A V; Silverman, N; Goldstein, S; Sabbah, H N

    2000-12-01

    Chronic heart failure (HF) is associated with morphologic abnormalities of cardiac mitochondria including hyperplasia, reduced organelle size and compromised structural integrity. In this study, we examined whether functional abnormalities of mitochondrial respiration are also present in myocardium of patients with advanced HF. Mitochondrial respiration was examined using a Clark electrode in an oxygraph cell containing saponin-skinned muscle bundles obtained from myocardium of failed explanted human hearts due to ischemic (ICM, n=9) or idiopathic dilated (IDC, n=9) cardiomyopathy. Myocardial specimens from five normal donor hearts served as controls (CON). Basal respiratory rate, respiratory rate after addition of the substrates glutamate and malate (V(SUB)), state 3 respiration (after addition of ADP, V(ADP)) and respiration after the addition of atractyloside (V(AT)) were measured in scar-free muscle bundles obtained from the subendocardial (ENDO) and subepicardial (EPI) thirds of the left ventricular (LV) free wall, interventricular septum and right ventricular (RV) free wall. There were no differences in basal and substrate-supported respiration between CON and HF regardless of etiology. V(ADP)was significantly depressed both in ICM and IDC compared to CON in all the regions studied. The respiratory control ratio, V(ADP)/V(AT), was also significantly decreased in HF compared to CON. In both ICM and IDC, V(ADP)was significantly lower in ENDO compared to EPI. The results indicate that mitochondrial respiration is abnormal in the failing human heart. The findings support the concept of low myocardial energy production in HF via oxidative phosphorylation, an abnormality with a potentially impact on global cardiac performance. Copyright 2000 Academic Press.

  18. The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

    PubMed

    Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

    2017-08-01

    Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  19. Dynamical Constants and Time Universals: A First Step toward a Metrical Definition of Ordered and Abnormal Cognition.

    PubMed

    Elliott, Mark A; du Bois, Naomi

    2017-01-01

    From the point of view of the cognitive dynamicist the organization of brain circuitry into assemblies defined by their synchrony at particular (and precise) oscillation frequencies is important for the correct correlation of all independent cortical responses to the different aspects of a given complex thought or object. From the point of view of anyone operating complex mechanical systems, i.e., those comprising independent components that are required to interact precisely in time, it follows that the precise timing of such a system is essential - not only essential but measurable, and scalable. It must also be reliable over observations to bring about consistent behavior, whatever that behavior is. The catastrophic consequence of an absence of such precision, for instance that required to govern the interference engine in many automobiles, is indicative of how important timing is for the function of dynamical systems at all levels of operation. The dynamics and temporal considerations combined indicate that it is necessary to consider the operating characteristic of any dynamical, cognitive brain system in terms, superficially at least, of oscillation frequencies. These may, themselves, be forensic of an underlying time-related taxonomy. Currently there are only two sets of relevant and necessarily systematic observations in this field: one of these reports the precise dynamical structure of the perceptual systems engaged in dynamical binding across form and time; the second, derived both empirically from perceptual performance data, as well as obtained from theoretical models, demonstrates a timing taxonomy related to a fundamental operator referred to as the time quantum. In this contribution both sets of theory and observations are reviewed and compared for their predictive consistency. Conclusions about direct comparability are discussed for both theories of cognitive dynamics and time quantum models. Finally, a brief review of some experimental data

  20. Temporal abnormalities in children with developmental dyscalculia.

    PubMed

    Vicario, Carmelo Mario; Rappo, Gaetano; Pepi, Annamaria; Pavan, Andrea; Martino, Davide

    2012-01-01

    Recent imaging studies have associated Developmental dyscalculia (DD) to structural and functional alterations corresponding Parietal and the Prefrontal cortex (PFC). Since these areas were shown also to be involved in timing abilities, we hypothesized that time processing is abnormal in DD. We compared time processing abilities between 10 children with pure DD (8 years old) and 11 age-matched healthy children. Results show that the DD group underestimated duration of a sub-second scale when asked to perform a time comparison task. The timing abnormality observed in our DD participants is consistent with evidence of a shared fronto-parietal neural network for representing time and quantity.

  1. Nonpathologizing trauma interventions in abnormal psychology courses.

    PubMed

    Hoover, Stephanie M; Luchner, Andrew F; Pickett, Rachel F

    2016-01-01

    Because abnormal psychology courses presuppose a focus on pathological human functioning, nonpathologizing interventions within these classes are particularly powerful and can reach survivors, bystanders, and perpetrators. Interventions are needed to improve the social response to trauma on college campuses. By applying psychodynamic and feminist multicultural theory, instructors can deliver nonpathologizing interventions about trauma and trauma response within these classes. We recommend class-based interventions with the following aims: (a) intentionally using nonpathologizing language, (b) normalizing trauma responses, (c) subjectively defining trauma, (d) challenging secondary victimization, and (e) questioning the delineation of abnormal and normal. The recommendations promote implications for instructor self-reflection, therapy interventions, and future research.

  2. Pregnancy outcomes among patients with recurrent pregnancy loss and uterine anatomic abnormalities.

    PubMed

    Gabbai, Daniel; Harlev, Avi; Friger, Michael; Steiner, Naama; Sergienko, Ruslan; Kreinin, Andrey; Bashiri, Asher

    2017-07-25

    Different etiologies for recurrent pregnancy loss have been identified, among them are: anatomical, endocrine, genetic, chromosomal and thrombophilia pathologies. To assess medical and obstetric characteristics, and pregnancy outcomes, among women with uterine abnormalities and recurrent pregnancy loss (RPL). This study also aims to assess the impact of uterine anatomic surgical correction on pregnancy outcomes. A retrospective case control study of 313 patients with two or more consecutive pregnancy losses followed by a subsequent (index) pregnancy. Anatomic abnormalities were detected in 80 patients. All patients were evaluated and treated in the RPL clinic at Soroka University Medical Center. Out of 80 patients with uterine anatomic abnormalities, 19 underwent surgical correction, 32 did not and 29 had no clear record of surgical intervention, and thus were excluded from this study. Women with anatomic abnormalities had a higher rate of previous cesarean section (18.8% vs. 8.6%, P=0.022), tended to have a lower number of previous live births (1.05 vs. 1.37, P=0.07), and a higher rate of preterm delivery (22.9% vs. 10%, P=0.037). Using multivariate logistic regression analysis, anatomic abnormality was identified as an independent risk factor for RPL in patients with previous cesarean section after controlling for place of residence, positive genetic/autoimmune/endocrine workup, and fertility problems (OR 7.22; 95% CI 1.17-44.54, P=0.03). Women suffering from anatomic abnormalities tended to have a higher rate of pregnancy loss compared to those without anatomic abnormalities (40% vs. 30.9%, P=0.2). The difference in pregnancy loss rate among women who underwent surgical correction compared to those who did not was not statistically significant. In patients with previous cesarean section, uterine abnormality is an independent risk factor for pregnancy loss. Surgical correction of uterine abnormalities among RPL patients might have the potential to improve live

  3. Follow-Up of Abnormal Breast and Colorectal Cancer Screening by Race/Ethnicity.

    PubMed

    McCarthy, Anne Marie; Kim, Jane J; Beaber, Elisabeth F; Zheng, Yingye; Burnett-Hartman, Andrea; Chubak, Jessica; Ghai, Nirupa R; McLerran, Dale; Breen, Nancy; Conant, Emily F; Geller, Berta M; Green, Beverly B; Klabunde, Carrie N; Inrig, Stephen; Skinner, Celette Sugg; Quinn, Virginia P; Haas, Jennifer S; Schnall, Mitchell; Rutter, Carolyn M; Barlow, William E; Corley, Douglas A; Armstrong, Katrina; Doubeni, Chyke A

    2016-10-01

    Timely follow-up of abnormal tests is critical to the effectiveness of cancer screening, but may vary by screening test, healthcare system, and sociodemographic group. Timely follow-up of abnormal mammogram and fecal occult blood testing or fecal immunochemical tests (FOBT/FIT) were compared by race/ethnicity using Population-Based Research Optimizing Screening through Personalized Regimens consortium data. Participants were women with an abnormal mammogram (aged 40-75 years) or FOBT/FIT (aged 50-75 years) in 2010-2012. Analyses were performed in 2015. Timely follow-up was defined as colonoscopy ≤3 months following positive FOBT/FIT; additional imaging or biopsy ≤3 months following Breast Imaging Reporting and Data System Category 0, 4, or 5 mammograms; or ≤9 months following Category 3 mammograms. Logistic regression was used to model receipt of timely follow-up adjusting for study site, age, year, insurance, and income. Among 166,602 mammograms, 10.7% were abnormal; among 566,781 FOBT/FITs, 4.3% were abnormal. Nearly 96% of patients with abnormal mammograms received timely follow-up versus 68% with abnormal FOBT/FIT. There was greater variability in receipt of follow-up across healthcare systems for positive FOBT/FIT than for abnormal mammograms. For mammography, black women were less likely than whites to receive timely follow-up (91.8% vs 96.0%, OR=0.71, 95% CI=0.51, 0.97). For FOBT/FIT, Hispanics were more likely than whites to receive timely follow-up than whites (70.0% vs 67.6%, OR=1.12, 95% CI=1.04, 1.21). Timely follow-up among women was more likely for abnormal mammograms than FOBT/FITs, with small variations in follow-up rates by race/ethnicity and larger variation across healthcare systems. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

  4. Granulocyte, monocyte and blast immunophenotype abnormalities in acute myeloid leukemia with myelodysplasia-related changes.

    PubMed

    Ayar, Sonali P; Ravula, Sreelakshmi; Polski, Jacek M

    2014-01-01

    Little literature exists regarding granulocyte and monocyte immunophenotype abnormalities in Acute Myeloid Leukemia (AML). We hypothesized that granulocyte and monocyte immunophenotype abnormalities are common in AML, and especially in AML with myelodysplasia-related changes (AMLMRC). Bone marrow or peripheral blood specimens from 48 cases of AML and 22 cases of control specimens were analyzed by flow cytometric immunophenotyping. Granulocyte, monocyte, and blast immunophenotype abnormalities were compared between cases of AML versus controls and AMLMRC versus AML without myelodysplasia. The results revealed that granulocyte, monocyte, and blast abnormalities were more common in AMLMRC than in AML without myelodysplasia or control cases. The difference reached statistical significance for abnormalities of granulocytes and abnormalities in all cells of interest. From the numerous individual abnormalities, only CD25 expression in blasts was significantly more prevalent in AMLMRC in this study. We conclude that detection of granulocyte, monocyte, and blast immunophenotype abnormalities can contribute to the diagnosis of AMLMRC.

  5. Association of MTHFR polymorphisms and chromosomal abnormalities in leukemia.

    PubMed

    Sinthuwiwat, Thivaratana; Poowasanpetch, Phanasit; Wongngamrungroj, Angsana; Soonklang, Kamonwan; Promso, Somying; Auewarakul, Chirayu; Tocharoentanaphol, Chintana

    2012-01-01

    Genetic variation in MTHFR gene might explain the interindividual differences in the reduction of DNA repaired and the increase of chromosome breakage and damage. Nowadays, chromosomal rearrangement is recognized as a major cause of lymphoid malignancies. In addition, the association of MTHFR polymorphisms with aneuploidy was found in several studies, making the MTHFR gene as a good candidate for leukemia etiology. Therefore, in this study, we investigated the common sequence variation, 677C>T and 1298A>C in the MTHFR gene of 350 fixed cell specimens archived after chromosome analysis. The distribution of the MTHFR polymorphisms frequency was compared in leukemic patients with structural chromosome abnormality and chromosome aneuploidy, as well as in those with no evidence of chromosome abnormalities. We observed a significant decrease in the distribution of T allele in 677C>T polymorphisms among patients with chromosomal abnormalities including both structural aberration and aneuploidy. The same significance result also found in patients with structural aberration when compare with the normal karyotype patients. Suggesting that polymorphism in the MTHFR gene was involved in chromosome abnormalities of leukemia. However, further investigation on the correlation with the specific types of chromosomal aberrations is needed.

  6. A functional Magnetic Resonance Imaging study of neurohemodynamic abnormalities during emotion processing in subjects at high risk for schizophrenia

    PubMed Central

    Venkatasubramanian, Ganesan; Puthumana, Dawn Thomas K.; Jayakumar, Peruvumba N.; Gangadhar, B. N.

    2010-01-01

    Background: Emotion processing abnormalities are considered among the core deficits in schizophrenia. Subjects at high risk (HR) for schizophrenia also show these deficits. Structural neuroimaging studies examining unaffected relatives at high risk for schizophrenia have demonstrated neuroanatomical abnormalities involving neo-cortical and sub-cortical brain regions related to emotion processing. The brain functional correlates of emotion processing in these HR subjects in the context of ecologically valid, real-life dynamic images using functional Magnetic Resonance Imaging (fMRI) has not been examined previously. Aim: To examine the neurohemodynamic abnormalities during emotion processing in unaffected subjects at high risk for schizophrenia in comparison with age-, sex-, handedness- and education-matched healthy controls, using fMRI. Materials and Methods: HR subjects for schizophrenia (n=17) and matched healthy controls (n=16) were examined. The emotion processing of fearful facial expression was examined using a culturally appropriate and valid tool for Indian subjects. The fMRI was performed in a 1.5-T scanner during an implicit emotion processing paradigm. The fMRI analyses were performed using the Statistical Parametric Mapping 2 (SPM2) software. Results: HR subjects had significantly reduced brain activations in left insula, left medial frontal gyrus, left inferior frontal gyrus, right cingulate gyrus, right precentral gyrus and right inferior parietal lobule. Hypothesis-driven region-of-interest analysis revealed hypoactivation of right amygdala in HR subjects. Conclusions: Study findings suggest that neurohemodynamic abnormalities involving limbic and frontal cortices could be potential indicators for increased vulnerability toward schizophrenia. The clinical utility of these novel findings in predicting the development of psychosis needs to be evaluated. PMID:21267363

  7. Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins.

    PubMed

    Sperling, L; Kiil, C; Larsen, L U; Brocks, V; Wojdemann, K R; Qvist, I; Schwartz, M; Jørgensen, C; Espersen, G; Skajaa, K; Bang, J; Tabor, A

    2007-05-01

    To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies. Copyright (c) 2007 ISUOG.

  8. ELECTROCARDIOGRAPHIC ABNORMALITIES AMONG MEXICAN AMERICANS: CORRELATIONS WITH DIABETES, OBESITY, AND THE METABOLIC SYNDROME.

    PubMed

    Queen, Saulette R; Smulevitz, Beverly; Rentfro, Anne R; Vatcheva, Kristina P; Kim, Hyunggun; McPherson, David D; Hanis, Craig L; Fisher-Hoch, Susan P; McCormick, Joseph B; Laing, Susan T

    2012-04-01

    Resting ischemic electrocardiographic abnormalities have been associated with cardiovascular mortality. Simple markers of abnormal autonomic tone have also been associated with diabetes, obesity, and the metabolic syndrome in some populations. Data on these electrocardiographic abnormalities and correlations with coronary risk factors are lacking among Mexican Americans wherein these conditions are prevalent. This study aimed to evaluate the prevalent resting electrocardiographic abnormalities among community-dwelling Mexican Americans, and correlate these findings with coronary risk factors, particularly diabetes, obesity, and the metabolic syndrome. Study subjects (n=1280) were drawn from the Cameron County Hispanic Cohort comprised of community-dwelling Mexican Americans living in Brownsville, Texas at the United States-Mexico border. Ischemic electrocardiographic abnormalities were defined as presence of ST/T wave abnormalities suggestive of ischemia, abnormal Q waves, and left bundle branch block. Parameters that reflect autonomic tone, such as heart rate-corrected QT interval and resting heart rate, were also measured. Ischemic electrocardiographic abnormalities were more prevalent among older persons and those with hypertension, diabetes, obesity, and the metabolic syndrome. Subjects in the highest quartiles of QTc interval and resting heart rate were also more likely to be diabetic, hypertensive, obese, or have the metabolic syndrome. Among Mexican Americans, persons with diabetes, obesity, and the metabolic syndrome were more likely to have ischemic electrocardiographic abnormalities, longer QTc intervals, and higher resting heart rates. A resting electrocardiogram can play a complementary role in the comprehensive evaluation of cardiovascular risk in this minority population.

  9. Prevalence and distribution of congenital abnormalities in Turkey: differences between the prenatal and postnatal periods.

    PubMed

    Oztarhan, Kazim; Gedikbasi, Ali; Yildirim, Dogukan; Arslan, Oguz; Adal, Erdal; Kavuncuoglu, Sultan; Ozbek, Sibel; Ceylan, Yavuz

    2010-12-01

    The aim of this study was to determine the distribution of cases associated with congenital abnormalities during the following three periods: pregnancy, birth, and the neonatal period. This was a retrospective study of cases between 2002 and 2006. All abnormal pregnancies, elective terminations of pregnancies, stillbirths, and births with congenital abnormalities managed in the Neonatology Unit were classified based on the above distribution scheme. During the 5-year study period, 1906 cases with congenital abnormalities were recruited, as follows: 640 prenatally detected and terminated cases, with most abnormalities related to the central nervous system, chromosomes, and urogenital system (56.7%, 12.7%, and 8.9%, respectively); 712 neonates with congenital abnormalities (congenital heart disease [49.2%], central nervous system abnormalities [14.7%], and urogenital system abnormalities [12.9%]); and hospital stillbirths, of which 34.2% had malformations (220 prenatal cases [34.4%] had multiple abnormalities, whereas 188 liveborn cases [26.4%] had multiple abnormalities). The congenital abnormalities rate between 2002 and 2006 was 2.07%. Systematic screening for fetal anomalies is the primary means for identification of affected pregnancies. © 2010 The Authors. Congenital Anomalies © 2010 Japanese Teratology Society.

  10. Guidelines on the management of abnormal liver blood tests

    PubMed Central

    Cramb, Rob; Davison, Suzanne M; Dillon, John F; Foulerton, Mark; Godfrey, Edmund M; Hall, Richard; Harrower, Ulrike; Hudson, Mark; Langford, Andrew; Mackie, Anne; Mitchell-Thain, Robert; Sennett, Karen; Sheron, Nicholas C; Verne, Julia; Walmsley, Martine; Yeoman, Andrew

    2018-01-01

    These updated guidelines on the management of abnormal liver blood tests have been commissioned by the Clinical Services and Standards Committee (CSSC) of the British Society of Gastroenterology (BSG) under the auspices of the liver section of the BSG. The original guidelines, which this document supersedes, were written in 2000 and have undergone extensive revision by members of the Guidelines Development Group (GDG). The GDG comprises representatives from patient/carer groups (British Liver Trust, Liver4life, PBC Foundation and PSC Support), elected members of the BSG liver section (including representatives from Scotland and Wales), British Association for the Study of the Liver (BASL), Specialist Advisory Committee in Clinical Biochemistry/Royal College of Pathology and Association for Clinical Biochemistry, British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN), Public Health England (implementation and screening), Royal College of General Practice, British Society of Gastrointestinal and Abdominal Radiologists (BSGAR) and Society of Acute Medicine. The quality of evidence and grading of recommendations was appraised using the AGREE II tool. These guidelines deal specifically with the management of abnormal liver blood tests in children and adults in both primary and secondary care under the following subheadings: (1) What constitutes an abnormal liver blood test? (2) What constitutes a standard liver blood test panel? (3) When should liver blood tests be checked? (4) Does the extent and duration of abnormal liver blood tests determine subsequent investigation? (5) Response to abnormal liver blood tests. They are not designed to deal with the management of the underlying liver disease. PMID:29122851

  11. Alopecia in four kittens caused by abnormal maternal licking behaviour.

    PubMed

    Fanton, N; Michelazzi, M; Cornegliani, L

    2015-11-01

    Abnormal maternal behaviour has been reported in cats, but is generally not included among the causes of alopecia in kittens. A litter of four kittens, 2 months old, was referred for evaluation of facial alopecia of differing severity. The 2-year-old queen was unaffected. Dermatological examination of the kittens did not find any infectious cause. Trichograms showed broken hair shafts with longitudinal splitting. Congenital alopecia was unlikely based on the clinical presentation. A behavioural consultation revealed abnormal grooming behaviour by the mother, who chewed and removed the hair from the kittens. The kittens were separated from the queen and alopecia resolved within a few weeks. To the authors' knowledge, this is the first report of alopecia caused by abnormal maternal licking behaviour. Abnormal maternal behaviour should be considered in cases of alopecia affecting a litter of kittens, when infectious and congenital causes have been ruled out. © 2015 Australian Veterinary Association.

  12. Plasma genetic and genomic abnormalities predict treatment response and clinical outcome in advanced prostate cancer.

    PubMed

    Xia, Shu; Kohli, Manish; Du, Meijun; Dittmar, Rachel L; Lee, Adam; Nandy, Debashis; Yuan, Tiezheng; Guo, Yongchen; Wang, Yuan; Tschannen, Michael R; Worthey, Elizabeth; Jacob, Howard; See, William; Kilari, Deepak; Wang, Xuexia; Hovey, Raymond L; Huang, Chiang-Ching; Wang, Liang

    2015-06-30

    Liquid biopsies, examinations of tumor components in body fluids, have shown promise for predicting clinical outcomes. To evaluate tumor-associated genomic and genetic variations in plasma cell-free DNA (cfDNA) and their associations with treatment response and overall survival, we applied whole genome and targeted sequencing to examine the plasma cfDNAs derived from 20 patients with advanced prostate cancer. Sequencing-based genomic abnormality analysis revealed locus-specific gains or losses that were common in prostate cancer, such as 8q gains, AR amplifications, PTEN losses and TMPRSS2-ERG fusions. To estimate tumor burden in cfDNA, we developed a Plasma Genomic Abnormality (PGA) score by summing the most significant copy number variations. Cox regression analysis showed that PGA scores were significantly associated with overall survival (p < 0.04). After androgen deprivation therapy or chemotherapy, targeted sequencing showed significant mutational profile changes in genes involved in androgen biosynthesis, AR activation, DNA repair, and chemotherapy resistance. These changes may reflect the dynamic evolution of heterozygous tumor populations in response to these treatments. These results strongly support the feasibility of using non-invasive liquid biopsies as potential tools to study biological mechanisms underlying therapy-specific resistance and to predict disease progression in advanced prostate cancer.

  13. Abnormal rich club organization and impaired correlation between structural and functional connectivity in migraine sufferers.

    PubMed

    Li, Kang; Liu, Lijun; Yin, Qin; Dun, Wanghuan; Xu, Xiaolin; Liu, Jixin; Zhang, Ming

    2017-04-01

    Because of the unique position of the topologically central role of densely interconnected brain hubs, our study aimed to investigate whether these regions and their related connections would be particularly vulnerable to migraine. In our study, we explored the rich club structure and its role in global functional dynamics in 30 patients with migraine without aura and 30 healthy controls. DTI and resting fMRI were used to construct structural connectivity (SC) and functional connectivity (FC) networks. An independent replication data set of 26 patients and 26 controls was included to replicate and validate significant findings. As compared with the controls, the structural networks of patients exhibited altered rich club organization with higher level of feeder connection density, abnormal small-world organization with increased global efficiency and decreased strength of SC-FC coupling. As these abnormal topological properties and headache attack duration exhibited a significant association with increased density of feeder connections, our results indicated that migraine may be characterized by a selective alteration of the structural connectivity of the rich club regions, tending to have higher 'bridgeness' with non-rich club regions, which may increase the integration among pain-related brain circuits with more excitability but less inhibition for the modulation of migraine.

  14. Cardiac Abnormalities in Primary Hyperoxaluria

    PubMed Central

    Mookadam, Farouk; Smith, Travis; Jiamsripong, Panupong; Moustafa, Sherif E; Monico, Carla G.; Lieske, John C.; Milliner, Dawn S.

    2018-01-01

    Background In patients with primary hyperoxaluria (PH), oxalate overproduction can result in recurrent urolithiasis and nephrocalcinosis, which in some cases results in a progressive decline in renal function, oxalate retention, and systemic oxalosis involving bone, retina, arterial media, peripheral nerves, skin, and heart. Oxalosis involving the myocardium or conduction system can potentially lead to heart failure and fatal arrhythmias. Methods and Results A retrospective review of our institution’s database was conducted for all patients with a confirmed diagnosis of PH between 1/1948 and 1/2006 (n=103). Electrocardiogram (ECG) and echocardiography were used to identify cardiac abnormalities. Ninety-three patients fulfilled the inclusion criteria, 58% were male. Mean follow-up was 11.9 (median 8.8) years. In 38 patients who received an ECG or echocardiography, 31 were found to have any cardiac abnormalities. Cardiac findings correlated with decline in renal function. Conclusions Our data suggests that physicians caring for patients with PH should pay close attention to cardiac status, especially if renal function is impaired. PMID:20921818

  15. Multifocal visual evoked potential and automated perimetry abnormalities in strabismic amblyopes.

    PubMed

    Greenstein, Vivienne C; Eggers, Howard M; Hood, Donald C

    2008-02-01

    To compare visual field abnormalities obtained with standard automated perimetry (SAP) to those obtained with the multifocal visual evoked potential (mfVEP) technique in strabismic amblyopes. Humphrey 24-2 visual fields (HVF) and mfVEPs were obtained from each eye of 12 strabismic amblyopes. For the mfVEP, amplitudes and latencies were analyzed and probability plots were derived. Multifocal VEP and HVF hemifields were abnormal if they had clusters of two or more contiguous points at p < 0.01, or three or more contiguous points at p < 0.05 with at least one at p < 0.01. An eye was abnormal if it had an abnormal hemifield. On SAP, amblyopic eyes had significantly higher foveal thresholds (p = 0.003) and lower mean deviation values (p = 0.005) than fellow eyes. For the mfVEP, 11 amblyopic and 6 fellow eyes were abnormal. Of the 11 amblyopic eyes, 6 were abnormal on SAP. The deficits extended from the center to mid periphery. Monocular mfVEP latencies were significantly decreased for amblyopic eyes compared with control eyes (p < 0.0002). Both techniques revealed deficits in visual function across the visual field in strabismic amblyopes, but the mfVEP revealed deficits in fellow eyes and in more amblyopic eyes. In addition, mfVEP response latencies for amblyopic eyes were shorter than normal.

  16. Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments.

    PubMed

    Mattusch, Corinna; Kratzer, Stephan; Buerge, Martina; Kreuzer, Matthias; Engel, Tatiana; Kopp, Claudia; Biel, Martin; Hammelmann, Verena; Ying, Shui-Wang; Goldstein, Peter A; Kochs, Eberhard; Haseneder, Rainer; Rammes, Gerhard

    2015-05-01

    The thalamus is thought to be crucially involved in the anesthetic state. Here, we investigated the effect of the inhaled anesthetic xenon on stimulus-evoked thalamocortical network activity and on excitability of thalamocortical neurons. Because hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are key regulators of neuronal excitability in the thalamus, the effect of xenon on HCN channels was examined. The effects of xenon on thalamocortical network activity were investigated in acutely prepared brain slices from adult wild-type and HCN2 knockout mice by means of voltage-sensitive dye imaging. The influence of xenon on single-cell excitability in brain slices was investigated using the whole-cell patch-clamp technique. Effects of xenon on HCN channels were verified in human embryonic kidney cells expressing HCN2 channels. Xenon concentration-dependently diminished thalamocortical signal propagation. In neurons, xenon reduced HCN channel-mediated Ih current amplitude by 33.4 ± 12.2% (at -133 mV; n = 7; P = 0.041) and caused a left-shift in the voltage of half-maximum activation (V1/2) from -98.8 ± 1.6 to -108.0 ± 4.2 mV (n = 8; P = 0.035). Similar effects were seen in human embryonic kidney cells. The impairment of HCN channel function was negligible when intracellular cyclic adenosine monophosphate level was increased. Using HCN2 mice, we could demonstrate that xenon did neither attenuate in vitro thalamocortical signal propagation nor did it show sedating effects in vivo. Here, we clearly showed that xenon impairs HCN2 channel function, and this impairment is dependent on intracellular cyclic adenosine monophosphate levels. We provide evidence that this effect reduces thalamocortical signal propagation and probably contributes to the hypnotic properties of xenon.

  17. A robust real-time abnormal region detection framework from capsule endoscopy images

    NASA Astrophysics Data System (ADS)

    Cheng, Yanfen; Liu, Xu; Li, Huiping

    2009-02-01

    In this paper we present a novel method to detect abnormal regions from capsule endoscopy images. Wireless Capsule Endoscopy (WCE) is a recent technology where a capsule with an embedded camera is swallowed by the patient to visualize the gastrointestinal tract. One challenge is one procedure of diagnosis will send out over 50,000 images, making physicians' reviewing process expensive. Physicians' reviewing process involves in identifying images containing abnormal regions (tumor, bleeding, etc) from this large number of image sequence. In this paper we construct a novel framework for robust and real-time abnormal region detection from large amount of capsule endoscopy images. The detected potential abnormal regions can be labeled out automatically to let physicians review further, therefore, reduce the overall reviewing process. In this paper we construct an abnormal region detection framework with the following advantages: 1) Trainable. Users can define and label any type of abnormal region they want to find; The abnormal regions, such as tumor, bleeding, etc., can be pre-defined and labeled using the graphical user interface tool we provided. 2) Efficient. Due to the large number of image data, the detection speed is very important. Our system can detect very efficiently at different scales due to the integral image features we used; 3) Robust. After feature selection we use a cascade of classifiers to further enforce the detection accuracy.

  18. Signs and symptoms of developmental abnormalities of the genitourinary tract.

    PubMed

    Nogueira, Paulo Cesar Koch; Paz, Isabel de Pádua

    2016-01-01

    The abnormalities of the genitourinary tract development are the leading cause of chronic kidney disease (CKD) in children. The diagnosis of this disease in Brazil is late and incomplete, which results in increased morbidity and mortality in this age group. Early diagnosis of this condition is the prerogative of generalist pediatricians, and the aim of this study was to review the clinical signs and symptoms associated with developmental abnormalities of the genitourinary tract. Based on the description of a symbolic clinical case, the authors conducted a non-systematic review of medical literature. The results suggest that the following data should be used as a warning for early diagnosis of affected children: (a) combined urinary tract abnormalities (chromosomal abnormalities; sequence of malformations [VACTERLand Prune-Belly]; and musculoskeletal, digestive tract, heart, and nervous system malformations); (b) previous history (congenital anomalies of the kidney and urinary tract [CAKUT] in the family, low birth weight, and oligoamnios); (c) clinical signs (polyuria/nocturia, urinary tract infection, systemic arterial hypertension, failure to thrive, weak urinary stream, difficulty to start urination, distended bladder, non-monosymptomatic enuresis, urinary/urge incontinence, and bowel and bladder dysfunction); and (d) pre- and postnatal ultrasonographic alterations (increased anteroposterior diameter of the renal pelvis, mainly in the third trimester of pregnancy; single kidney; hydronephrosis associated with other abnormalities; and hydronephrosis with parenchymal involvement in the post-neonatal assessment). The suggestions shown here can help the pediatrician to establish clinical hypotheses for the early diagnosis of developmental abnormalities of the genitourinary tract without resorting to expensive and invasive procedures. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Occipitoparietal epilepsy, hippocampal atrophy, and congenital developmental abnormalities.

    PubMed

    Lawn, N; Londono, A; Sawrie, S; Morawetz, R; Martin, R; Gilliam, F; Faught, E; Kuzniecky, R

    2000-12-01

    Diagnostic uncertainty may arise in patients with occipitoparietal epilepsy when there is neuroimaging evidence of a posterior quadrant lesion and coexistent hippocampal abnormalities ("dual pathology"). It is not known whether hippocampal atrophy (HA) in these patients results from seizure propagation to temporolimbic structures or whether it is part of the pathological process underlying the occipitoparietal epilepsy. Clarification of this issue may have a significant bearing on the management of these patients. We studied 20 patients with occipitoparietal epilepsy and neuroimaging or pathologic evidence of a congenital developmental abnormality. Normalized hippocampal volumes were obtained in all patients. The medical records and video-EEG recordings were analyzed to correlate the MRI findings with clinical data, seizure semiology, and EEG findings. HA was found in seven patients (35%). Neuroimaging abnormalities concordant with the side of HA were seen in all cases. There was clinical or EEG evidence of temporal spread in 12 patients. There was no correlation between the presence of HA and temporal lobe spread. The only clinical factor associated with HA in this series was a younger age of seizure onset. HA in patients with occipitoparietal epilepsy due to congenital developmental abnormalities is most likely to be a marker of a more widespread process related to a common pathogenesis during prenatal or perinatal development. HA in these patients is unlikely to be the result of secondary spread from an extrahippocampal focus. Surgical treatment should be tailored toward the primary epileptogenic zone rather the site of seizure spread.

  20. Lack of Association of ST-T Wave Abnormalities to Congenital Heart Disease in Neonates.

    PubMed

    Gorla, Sudheer R; Hsu, Daphne T; Kulkarni, Aparna

    2016-09-01

    ST-T wave (STTW) abnormalities have been described in 20-40% of normal newborns. We sought to describe the associations of these Electrocardiogram (ECG) abnormalities to perinatal course and congenital heart disease (CHD). A retrospective chart review was performed on all neonatal ECGs between January 2008 and March 2013 identified from electronic medical records. Electronic medical records were reviewed for perinatal course and maternal medical conditions. Neonates <37 weeks gestation, >3 days age, requiring hemodynamic support in the first 3 days, with oxygen saturation <90% on room air, or with arrhythmias and significant abnormalities of axis and voltage were excluded from the analysis. ST segment elevation or depression of >2 mm in at least one lead and flat or inverted T waves in at least one lead except aVR were considered abnormal. Statistical relationships were explored between STTW abnormalities, perinatal variables and CHD. ECGs were performed on 1043 neonates, of which 664 were included. STTW abnormalities were found in 236 (35.5%) neonates. T wave abnormalities were identified in 191 (28.7%), ST segment abnormalities in 77 (11.6%) and both on 32 (4.8%) neonates. No relationship was found between the ECG abnormalities and perinatal variables, except maternal cefazolin administration during labor. Noncritical CHD was diagnosed by echocardiography in 59/84; STTW abnormalities were seen in 17/59 (29%) patients with and 9/25 (34%) without noncritical CHD, P = .6. STTW abnormalities on ECG are commonly found in 35.5% of normal neonates and do not predict noncritical CHD. © 2016 Wiley Periodicals, Inc.

  1. Thalamofrontal neurodevelopment in new-onset pediatric idiopathic generalized epilepsy.

    PubMed

    Pulsipher, D T; Dabbs, K; Tuchsherer, V; Sheth, R D; Koehn, M A; Hermann, B P; Seidenberg, M

    2011-01-04

    Quantitative MRI techniques have demonstrated thalamocortical abnormalities in idiopathic generalized epilepsy (IGE). However, there are few studies examining IGE early in its course and the neurodevelopmental course of this region is not adequately defined. We examined the 2-year developmental course of the thalamus and frontal lobes in pediatric new-onset IGE (i.e., within 12 months of diagnosis). We performed whole-brain MRI in 22 patients with new-onset IGE and 36 age-matched healthy controls. MRI was repeated 24 months after baseline MRI. Quantitative volumetrics were used to examine thalamic and frontal lobe volumes. The IGE group showed significant differences in thalamic volume within 1 year of seizure onset (baseline) and went on to show thalamic volume loss at a significantly faster rate than healthy control children over the 2-year interval. The control group also showed a significantly greater increase in frontal white matter expansion than the IGE group. In contrast, frontal lobe gray matter volume differences were moderate at baseline and persisted over time, indicating similar developmental trajectories with differences early in the disease process that are maintained. Brain tissue abnormalities in thalamic and frontal regions can be identified very early in the course of IGE and an abnormal trajectory of growth continues over a 2-year interval.

  2. Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia

    PubMed Central

    Sturm, Virginia E.; Seeley, William W.; Miller, Bruce L.; Kramer, Joel H.; Rosen, Howard J.

    2014-01-01

    Behavioural variant frontotemporal dementia is characterized by abnormal responses to primary reward stimuli such as food, sex and intoxicants, suggesting abnormal functioning of brain circuitry mediating reward processing. The goal of this analysis was to determine whether abnormalities in reward-seeking behaviour in behavioural variant frontotemporal dementia are correlated with atrophy in regions known to mediate reward processing. Review of case histories in 103 patients with behavioural variant frontotemporal dementia identified overeating or increased sweet food preference in 80 (78%), new or increased alcohol or drug use in 27 (26%), and hypersexuality in 17 (17%). For each patient, a primary reward-seeking score of 0–3 was created with 1 point given for each target behaviour (increased seeking of food, drugs, or sex). Voxel-based morphometry performed in 91 patients with available imaging revealed that right ventral putamen and pallidum atrophy correlated with higher reward-seeking scores. Each of the reward-related behaviours involved partially overlapping right hemisphere reward circuit regions including putamen, globus pallidus, insula and thalamus. These findings indicate that in some patients with behavioural variant frontotemporal dementia, low volume of subcortical reward-related structures is associated with increased pursuit of primary rewards, which may be a product of increased thalamocortical feedback. PMID:24740987

  3. Sleep abnormalities in children with Dravet syndrome.

    PubMed

    Dhamija, Radhika; Erickson, Maia K; St Louis, Erik K; Wirrell, Elaine; Kotagal, Suresh

    2014-05-01

    Mutations in the voltage-gated sodium channel SCN1A gene are responsible for the majority of Dravet syndrome cases. There is evidence that the Nav1.1 channel coded by the SCN1A gene is involved in sleep regulation. We evaluated sleep abnormalities in children with Dravet syndrome using nocturnal polysomnography. We identified six children at our institution with genetically confirmed Dravet syndrome who had also undergone formal sleep consultation with nocturnal polysomnography. Indications for polysomnography were parental concern of daytime fatigue or sleepiness, hyperactivity, inattention, disruptive behavior, nighttime awakenings, or nocturnal seizures. Sleep studies were scored according to guidelines of the American Academy of Sleep Medicine and non-rapid eye movement cyclic alternating pattern was visually identified and scored according to established methods. The mean age of the subjects at the time of polysomnography was 6 years. Standard polysomnography did not show any consistent abnormalities in the obstructive or central apnea index, arousal index, sleep efficiency, or architecture. Cyclic alternating pattern analysis on five patients showed an increased mean rate of 50.3% (vs 31% to 34% in neurological normal children) with a mild increase in A1 subtype of 89.4% (vs 84.5%). A2/A3 subtype (5.3% vs 7.3%) and B phase duration (22.4 vs 24.7 seconds) were similar to previously reported findings in neurologically normal children. Despite parental concerns for sleep disturbance in patients with Dravet syndrome, we could not identify abnormalities in sleep macroarchitecture. Non-rapid eye movement sleep microarchitecture was, however, abnormal, with increased A1 subtype, somewhat resembling a tracé alternant pattern of neonates and possibly suggestive of cortical synaptic immaturity in Dravet syndrome. Larger studies are needed to replicate these results. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. MRI appearance of surgically proven abnormal accessory anterior-inferior tibiofibular ligament (Bassett's ligament).

    PubMed

    Subhas, Naveen; Vinson, Emily N; Cothran, R Lee; Santangelo, James R; Nunley, James A; Helms, Clyde A

    2008-01-01

    A thickened accessory anterior-inferior tibiofibular ligament (Bassett's ligament) of the ankle can be a cause of ankle impingement. Its imaging appearance is not well described. The purpose of this study was to determine if the ligament could be identified on magnetic resonance imaging (MRI), to determine associated abnormalities, and to determine if MRI could be used to differentiate normal from abnormal. Eighteen patients with a preoperative ankle MRI and an abnormal Bassett's ligament reported at surgery were found retrospectively. A separate cohort of 18 patients was selected as a control population. The presence of Bassett's ligament and its thickness were noted. The integrity and appearance of the lateral ankle ligaments, talar dome cartilage, and anterolateral gutter were also noted. In 34 of the 36 cases (94%), Bassett's ligament was identified on MRI. The ligament was seen in all three imaging planes and most frequently in the axial plane. The mean thickness of the ligament in the surgically abnormal cases was 2.37 mm, compared with 1.87 mm in the control with a p value=0.015 (t test). Nine of the 18 abnormal cases (50%) had talar dome cartilage lesions as a result of contact with the ligament at surgery, with only 3 cases of high-grade defects seen on MRI. Fourteen of the 18 abnormal cases (78%) had of synovitis or scarring in the lateral gutter at surgery, with only 5 cases with scarring seen on MRI. The anterior-inferior tibiofibular ligament was abnormal or torn in 8 of the 18 abnormal cases (44%) by MRI and confirmed in only 3 cases at surgery. Bassett's ligament can be routinely identified on MRI and was significantly thicker in patients who had it resected at surgery. An abnormal Bassett's ligament is often present in the setting of a normal anterior-inferior tibiofibular ligament. The cartilage abnormalities and synovitis associated with an abnormal Bassett's ligament are poorly detected by conventional MRI.

  5. Identification of a novel dynamic red blindness in human by event-related brain potentials.

    PubMed

    Zhang, Jiahua; Kong, Weijia; Yang, Zhongle

    2010-12-01

    Dynamic color is an important carrier that takes information in some special occupations. However, up to the present, there are no available and objective tests to evaluate dynamic color processing. To investigate the characteristics of dynamic color processing, we adopted two patterns of visual stimulus called "onset-offset" which reflected static color stimuli and "sustained moving" without abrupt mode which reflected dynamic color stimuli to evoke event-related brain potentials (ERPs) in primary color amblyopia patients (abnormal group) and subjects with normal color recognition ability (normal group). ERPs were recorded by Neuroscan system. The results showed that in the normal group, ERPs in response to the dynamic red stimulus showed frontal positive amplitudes with a latency of about 180 ms, a negative peak at about 240 ms and a peak latency of the late positive potential (LPP) in a time window between 290 and 580 ms. In the abnormal group, ERPs in response to the dynamic red stimulus were fully lost and characterized by vanished amplitudes between 0 and 800 ms. No significant difference was noted in ERPs in response to the dynamic green and blue stimulus between the two groups (P>0.05). ERPs of the two groups in response to the static red, green and blue stimulus were not much different, showing a transient negative peak at about 170 ms and a peak latency of LPP in a time window between 350 and 650 ms. Our results first revealed that some subjects who were not identified as color blindness under static color recognition could not completely apperceive a sort of dynamic red stimulus by ERPs, which was called "dynamic red blindness". Furthermore, these results also indicated that low-frequency ERPs induced by "sustained moving" may be a good and new method to test dynamic color perception competence.

  6. Methods and systems for detecting abnormal digital traffic

    DOEpatents

    Goranson, Craig A [Kennewick, WA; Burnette, John R [Kennewick, WA

    2011-03-22

    Aspects of the present invention encompass methods and systems for detecting abnormal digital traffic by assigning characterizations of network behaviors according to knowledge nodes and calculating a confidence value based on the characterizations from at least one knowledge node and on weighting factors associated with the knowledge nodes. The knowledge nodes include a characterization model based on prior network information. At least one of the knowledge nodes should not be based on fixed thresholds or signatures. The confidence value includes a quantification of the degree of confidence that the network behaviors constitute abnormal network traffic.

  7. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    PubMed

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

  8. Alternating Hemiplegia of Childhood-Related Neural and Behavioural Phenotypes in Na+,K+-ATPase α3 Missense Mutant Mice

    PubMed Central

    Kirshenbaum, Greer S.; Dawson, Neil; Mullins, Jonathan G. L.; Johnston, Tom H.; Drinkhill, Mark J.; Edwards, Ian J.; Fox, Susan H.; Pratt, Judith A.; Brotchie, Jonathan M.; Roder, John C.; Clapcote, Steven J.

    2013-01-01

    Missense mutations in ATP1A3 encoding Na+,K+-ATPase α3 have been identified as the primary cause of alternating hemiplegia of childhood (AHC), a motor disorder with onset typically before the age of 6 months. Affected children tend to be of short stature and can also have epilepsy, ataxia and learning disability. The Na+,K+-ATPase has a well-known role in maintaining electrochemical gradients across cell membranes, but our understanding of how the mutations cause AHC is limited. Myshkin mutant mice carry an amino acid change (I810N) that affects the same position in Na+,K+-ATPase α3 as I810S found in AHC. Using molecular modelling, we show that the Myshkin and AHC mutations display similarly severe structural impacts on Na+,K+-ATPase α3, including upon the K+ pore and predicted K+ binding sites. Behavioural analysis of Myshkin mice revealed phenotypic abnormalities similar to symptoms of AHC, including motor dysfunction and cognitive impairment. 2-DG imaging of Myshkin mice identified compromised thalamocortical functioning that includes a deficit in frontal cortex functioning (hypofrontality), directly mirroring that reported in AHC, along with reduced thalamocortical functional connectivity. Our results thus provide validation for missense mutations in Na+,K+-ATPase α3 as a cause of AHC, and highlight Myshkin mice as a starting point for the exploration of disease mechanisms and novel treatments in AHC. PMID:23527305

  9. Habitat quality affects the incidence of morphological abnormalities in the endangered salamander Ambystoma ordinarium

    PubMed Central

    2017-01-01

    Identification of early warning signals previous to the occurrence of population decline or extinction is a major challenge for the conservation of animal species. Prevalence of morphological abnormalities in a population can be one of these signals. We registered morphological abnormalities in the salamander Ambystoma ordinarium. We also evaluated the relation between habitat quality and the prevalence of abnormalities in this species. We used scores from rapid bioassessment protocols (RBPs) to assess the habitat quality of streams inhabited by A. ordinarium. A preliminary survey indicated that of 29 streams where this species has been historically registered, 13 might have few or no A. ordinarium. The association between habitat quality and the incidence of morphological abnormalities was evaluated in these 16 streams. Of 502 sampled individuals, 224 (44.62%) had at least one body abnormality. Of the 224 individuals with body abnormalities, 84 (37.5%) presented more than one abnormality. Of a total of 5,522 evaluated morphological characters, 344 (6.74%) were abnormal. Partial loss of gills and missing digits were the most frequent abnormalities. Results of a binomial logistic regression indicated that the probability of a character of an individual to be abnormal was significantly associated with habitat quality; as the levels of the quality of the habitat increased, the prevalence of morphological abnormalities decreased. These results suggest that RBPs are a quick and useful method for assessing the habitat quality of streams inhabited by A. ordinarium. Given that RBPs provide rapid and cost-effective assessments of the ecological health of aquatic ecosystems, it will be important to test if the RBPs protocols can be used to rapidly assess habitat quality for other species of stream amphibians. The negative association between habitat quality and the prevalence of morpohological abnormalities that we found indicates that habitat condition plays an important

  10. Structural abnormality of the corticospinal tract in major depressive disorder

    PubMed Central

    2014-01-01

    Background Scientists are beginning to document abnormalities in white matter connectivity in major depressive disorder (MDD). Recent developments in diffusion-weighted image analyses, including tractography clustering methods, may yield improved characterization of these white matter abnormalities in MDD. In this study, we acquired diffusion-weighted imaging data from MDD participants and matched healthy controls. We analyzed these data using two tractography clustering methods: automated fiber quantification (AFQ) and the maximum density path (MDP) procedure. We used AFQ to compare fractional anisotropy (FA; an index of water diffusion) in these two groups across major white matter tracts. Subsequently, we used the MDP procedure to compare FA differences in fiber paths related to the abnormalities in major fiber tracts that were identified using AFQ. Results FA was higher in the bilateral corticospinal tracts (CSTs) in MDD (p’s < 0.002). Secondary analyses using the MDP procedure detected primarily increases in FA in the CST-related fiber paths of the bilateral posterior limbs of the internal capsule, right superior corona radiata, and the left external capsule. Conclusions This is the first study to implicate the CST and several related fiber pathways in MDD. These findings suggest important new hypotheses regarding the role of CST abnormalities in MDD, including in relation to explicating CST-related abnormalities to depressive symptoms and RDoC domains and constructs. PMID:25295159

  11. Developmental antecedents of abnormal eating attitudes and behaviors in adolescence.

    PubMed

    Le Grange, Daniel; O'Connor, Meredith; Hughes, Elizabeth K; Macdonald, Jacqui; Little, Keriann; Olsson, Craig A

    2014-11-01

    This study capitalizes on developmental data from an Australian population-based birth cohort to identify developmental markers of abnormal eating attitudes and behaviors in adolescence. The aims were twofold: (1) to develop a comprehensive path model identifying infant and childhood developmental correlates of Abnormal Eating Attitudes and Behaviors in adolescence, and (2) to explore potential gender differences. Data were drawn from a 30-year longitudinal study that has followed the health and development of a population based cohort across 15 waves of data collection from infancy since 1983: The Australian Temperament Project. Participants in this analysis were the 1,300 youth who completed the 11th survey at 15-16 years (1998) and who completed the eating disorder inventory at this time point. Developmental correlates of Abnormal Eating Attitudes and Behaviors in mid-adolescence were temperamental persistence, early gestational age, persistent high weight, teen depression, stronger peer relationships, maternal dieting behavior, and pubertal timing. Overall, these factors accounted for 28% of the variance in Abnormal Eating Attitudes and Behaviors at 15-16 years of age. Depressive symptoms, maternal dieting behavior, and early puberty were more important factors for girls. Late puberty was a more important factor for boys. Findings address an important gap in our understanding of the etiology of Abnormal Eating Attitudes and Behaviors in adolescence and suggest multiple targets for preventive intervention. © 2014 Wiley Periodicals, Inc.

  12. Diagnosis and treatment of abnormal dental pain.

    PubMed

    Fukuda, Ken-Ichi

    2016-03-01

    Most dental pain is caused by an organic problem such as dental caries, periodontitis, pulpitis, or trauma. Diagnosis and treatment of these symptoms are relatively straightforward. However, patients often also complain of abnormal dental pain that has a non-dental origin, whose diagnosis is challenging. Such abnormal dental pain can be categorized on the basis of its cause as referred pain, neuromodulatory pain, and neuropathic pain. When it is difficult to diagnose a patient's dental pain, these potential alternate causes should be considered. In this clinical review, we have presented a case of referred pain from the digastric muscle (Patient 1), of pulpectomized (Patient 2), and of pulpectomized pain (Patient 3) to illustrate referred, neuromodulatory, and neuropathic pain, respectively. The Patient 1 was advised muscle stretching and gentle massage of the trigger points, as well as pain relief using a nonsteroidal anti-inflammatory and the tricyclic antidepressant amitriptyline. The pain in Patient 2 was relieved completely by the tricyclic antidepressant amitriptyline. In Patient 3, the pain was controlled using either a continuous drip infusion of adenosine triphosphate or intravenous Mg2+ and lidocaine administered every 2 weeks. In each case of abnormal dental pain, the patient's diagnostic chart was used (Fig.2 and 3). Pain was satisfactorily relieved in all cases.

  13. 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

  14. Developmental abnormalities of the posterior pituitary gland.

    PubMed

    di Iorgi, Natascia; Secco, Andrea; Napoli, Flavia; Calandra, Erika; Rossi, Andrea; Maghnie, Mohamad

    2009-01-01

    While the molecular mechanisms of anterior pituitary development are now better understood than in the past, both in animals and in humans, little is known about the mechanisms regulating posterior pituitary development. The posterior pituitary gland is formed by the evagination of neural tissue from the floor of the third ventricle. It consists of the distal axons of the hypothalamic magnocellular neurones that shape the neurohypophysis. After its downward migration, it is encapsulated together with the ascending ectodermal cells of Rathke's pouch which form the anterior pituitary. By the end of the first trimester, this development is completed and vasopressin and oxytocin can be detected in neurohypophyseal tissue. Abnormal posterior pituitary migration such as the ectopic posterior pituitary lobe appearing at the level of median eminence or along the pituitary stalk have been reported in idiopathic GH deficiency or in subjects with HESX1, LHX4 and SOX3 gene mutations. Another intriguing feature of abnormal posterior pituitary development involves genetic forms of posterior pituitary neurodegeneration that have been reported in autosomal-dominant central diabetes insipidus and Wolfram disease. Defining the phenotype of the posterior pituitary gland can have significant clinical implications for management and counseling, as well as providing considerable insight into normal and abnormal mechanisms of posterior pituitary development in humans.

  15. Effect of Time-Dependent Pinning Pressure on Abnormal Grain Growth: Phase Field Simulation

    NASA Astrophysics Data System (ADS)

    Kim, Jeong Min; Min, Guensik; Shim, Jae-Hyeok; Lee, Kyung Jong

    2018-05-01

    The effect of the time-dependent pinning pressure of precipitates on abnormal grain growth has been investigated by multiphase field simulation with a simple precipitation model. The application of constant pinning pressure is problematic because it always induces abnormal grain growth or no grain growth, which is not reasonable considering the real situation. To produce time-dependent pinning pressure, both precipitation kinetics and precipitate coarsening kinetics have been considered with two rates: slow and fast. The results show that abnormal grain growth is suppressed at the slow precipitation rate. At the slow precipitation rate, the overall grain growth caused by the low pinning pressure in the early stage indeed plays a role in preventing abnormal grain growth by reducing the mobility advantage of abnormal grains. In addition, the fast precipitate coarsening rate tends to more quickly transform abnormal grain growth into normal grain growth by inducing the active growth of grains adjacent to the abnormal grains in the early stage. Therefore, the present study demonstrates that the time dependence of the pinning pressure of precipitates is a critical factor that determines the grain growth mode.

  16. Effect of Time-Dependent Pinning Pressure on Abnormal Grain Growth: Phase Field Simulation

    NASA Astrophysics Data System (ADS)

    Kim, Jeong Min; Min, Guensik; Shim, Jae-Hyeok; Lee, Kyung Jong

    2018-03-01

    The effect of the time-dependent pinning pressure of precipitates on abnormal grain growth has been investigated by multiphase field simulation with a simple precipitation model. The application of constant pinning pressure is problematic because it always induces abnormal grain growth or no grain growth, which is not reasonable considering the real situation. To produce time-dependent pinning pressure, both precipitation kinetics and precipitate coarsening kinetics have been considered with two rates: slow and fast. The results show that abnormal grain growth is suppressed at the slow precipitation rate. At the slow precipitation rate, the overall grain growth caused by the low pinning pressure in the early stage indeed plays a role in preventing abnormal grain growth by reducing the mobility advantage of abnormal grains. In addition, the fast precipitate coarsening rate tends to more quickly transform abnormal grain growth into normal grain growth by inducing the active growth of grains adjacent to the abnormal grains in the early stage. Therefore, the present study demonstrates that the time dependence of the pinning pressure of precipitates is a critical factor that determines the grain growth mode.

  17. Age-Specific Dynamics of Corpus Callosum Development in Children and its Peculiarities in Infantile Cerebral Palsy.

    PubMed

    Krasnoshchekova, E I; Zykin, P A; Tkachenko, L A; Aleksandrov, T A; Sereda, V M; Yalfimov, A N

    2016-10-01

    The age dynamics of corpus callosum development was studied on magnetic resonance images of the brain in children aged 2-11 years without neurological abnormalities and with infantile cerebral palsy. The areas of the total corpus callosum and its segments are compared in the midsagittal images. Analysis is carried out with the use of an original formula: proportion of areas of the anterior (genu, CC2; and anterior part, CC3) and posterior (isthmus, CC6 and splenium, CC7) segments: kCC=(CC2+CC3)×CC6/CC7. The results characterize age-specific dynamics of the corpus callosum development and can be used for differentiation, with high confidence, of the brain of children without neurological abnormalities from the brain patients with infantile cerebral palsy.

  18. Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches

    PubMed Central

    Banerjee, Kalpita; Munshi, Soumyabrata; Frank, David E.; Gibson, Gary E.

    2015-01-01

    Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer’s disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer's disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies. PMID:26077923

  19. Rate of abnormal osteoarticular radiographic findings in pediatric patients.

    PubMed

    Petit, P; Sapin, C; Henry, G; Dahan, M; Panuel, M; Bourlière-Najean, B; Chaumoitre, K; Devred, P

    2001-04-01

    The objective of our study was to assess the rate of abnormal radiographic findings in the most frequent osteoarticular locations of traumatic injury in a pediatric population. During two periods of 12 weeks each, all patients admitted to the pediatric emergency department for osteoarticular trauma who underwent radiography were prospectively included in this study. A connection was drawn between the rate of abnormal radiographic findings for the seven most frequently radiographed locations and the clinical findings. Of 3128 locations of trauma in 2470 children, only 22% of the radiographic examinations were considered to reveal abnormal findings. In decreasing order, the hand and fingers, the ankle, the wrist, the knee, the elbow, the foot and toes, and the forearm were the most frequently examined locations. The rate of abnormal findings was 25.7% for the hand and fingers, 9.0% for the ankle, 42.5% for the wrist, 9.5% for the knee, 33.3% for the elbow, 18.3% for the foot, and 43.2% for the forearm. When only the direct sign of fracture was taken into account, these rates decreased for the ankle and knee to 2.6% and 1.9%, respectively. There was always a significant link between the degree of clinical suspicion and the rate of abnormal radiographic findings. However, fewer than 50% of the cases with high clinical suspicion of fracture were radiographically confirmed. It appears necessary, especially in cases of lower limb trauma, to evaluate clinical tests, including the implementation of the Ottawa ankle rules, to reduce the number of unnecessary radiographic examinations. This reduction will improve some parameters of children's quality of life and will significantly decrease the cost of emergency care.

  20. Association of abnormal plasma bilirubin with aggressive HCC phenotype

    PubMed Central

    Carr, Brian I.; Guerra, Vito; Giannini, Edoardo G.; Farinati, Fabio; Ciccarese, Francesca; Rapaccini, Gian Ludovico; Marco, Maria Di; Benvegnù, Luisa; Zoli, Marco; Borzio, Franco; Caturelli, Eugenio; Chiaramonte, Maria; Trevisani, Franco

    2014-01-01

    Background Cirrhosis-related abnormal liver function is associated with predisposition to HCC, features in several HCC classification systems and is an HCC prognostic factor. Aims To examine the phenotypic tumor differences in HCC patients with normal or abnormal plasma bilirubin levels. Methods A 2,416 patient HCC cohort was studied and dichotomized into normal and abnormal plasma bilirubin groups. Their HCC characteristics were compared for tumor aggressiveness features, namely blood AFP levels, tumor size, presence of PVT and tumor multifocality. Results In the total cohort, elevated bilirubin levels were associated with higher AFP levels, increased PVT and multifocality and lower survival, despite similar tumor sizes. When different tumor size terciles were compared, similar results were found, even for small tumor size patients. A multiple logistic regression model for PVT or tumor multifocality showed increased OddsRatios for elevated levels of GGTP, bilirubin and AFP and for larger tumor sizes. Conclusions HCC patients with abnormal bilirubin levels had worse prognosis than patients with normal bilirubin. They also had increased incidence of PVT and tumor multifocality and higher AFP levels, in patients with both small and larger tumors. The results show an association between bilirubin levels and indices of HCC aggressiveness. PMID:24787296

  1. Conservative management of placenta previa complicated by abnormal placentation.

    PubMed

    Bręborowicz, Grzegorz H; Markwitz, Wiesław; Gaca, Michał; Koziołek, Agnieszka; Ropacka-Lesiak, Mariola; Dera, Anna; Brych, Mariusz; Szymankiewicz-Bręborowicz, Marta; Kruszyński, Grzegorz; Gruca-Stryjak, Karolina; Madejczyk, Mateusz; Szpera-Goździewicz, Agata; Krzyścin, Mariola

    2013-07-01

    Abnormal implantation of placenta previa is life-threatening condition. The purpose of this study was to evaluate the impact of the conservative management of pregnancies with such complication on maternal morbidity rate and the chance for uterine preservation (fertility). Eleven patients with abnormal implantation of placenta previa were analyzed prospectively. This complication was diagnosed antenatally by two-dimensional ultrasound and color flow Doppler. The following outcomes were analyzed: need for blood transfusion, admission and duration of stay in intensive care unit, infections, coagulopathies, time between cesarean section and delivery of placenta, hysterectomy and preservation of uterus. Among the 20 085 women who had a singleton gestation, 11 (0.054%) were identified with placenta previa with abnormal placentation. In five patients (group A), hysterectomy was performed because of hemorrhage or placenta ablation. In six patients (group B), conservative management succeeded and placenta were preserved. In group A, placenta were delivered earlier (2 d-8 weeks) in comparison with group B (6-15 weeks). Estimated blood loss during the delayed delivery of placenta was higher in the group with hysterectomy (respectively, 450-1600 and 300-500 ml). Conservative management of placenta previa with abnormal implantation decreases the risk of severe hemorrhage at the time of delivery and can preserve fertility.

  2. Sensorineural Deafness, Distinctive Facial Features and Abnormal Cranial Bones

    PubMed Central

    Gad, Alona; Laurino, Mercy; Maravilla, Kenneth R.; Matsushita, Mark; Raskind, Wendy H.

    2008-01-01

    The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype. PMID:18553554

  3. Abnormal dark-adapted electroretinogram in Best's vitelliform macular degeneration.

    PubMed

    Lachapelle, P; Quigley, M G; Polomeno, R C; Little, J M

    1988-10-01

    It is generally well accepted that in Best's vitelliform macular degeneration (BVMD) the electroretinogram (ERG) is normal whereas the electro-oculogram (EOG) is markedly abnormal. We describe a patient in whom BVMD was suspected on the basis of the clinical findings, EOG and family history (one of her daughters had the typical vitelliform lesion). However, her dark-adapted ERG was markedly abnormal. Similar anomalies were found in the dark-adapted ERG of the daughter. While the temporal features of the various ERG waves were well preserved, a substantial decrease in the amplitude of specific segments of the ERG signal was observed. A similar decrease in the amplitude of the oscillatory potentials was also found. We believe that this unusual combination of BVMD and abnormal dark-adapted ERG may be due to the reported reduced penetrance and variable expressivity of the BVMD gene(s).

  4. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed. © 2015 The Fisheries Society of the British Isles.

  5. Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias.

    PubMed

    Ocak, Z; Özlü, T; Ozyurt, O

    2013-06-01

    Recurrent pregnancy loss (RPL) which is generally known as >3 consecutive pregnancy losses before 20 weeks' gestation is seen in 0.5-2% of women. To evaluate the association of parental and fetal chromosomal abnormalities with recurrent pregnancy loss in our area and to analyze the frequency of three types of hereditary thrombophilia's; (MTHFR C677T polymorphisms, FV Leiden G1691A mutation and Prothrombin (factor II) G20210A mutation) in these female patients. The present case-control retrospective study was performed between February 2007 and December 2011 on 495 couples, who had two or more consecutive pregnancy losses before 20 weeks' gestation. We used conventional cytogenetic analysis and polymerase chain reaction-restriction fragment length polymorphism. Parental chromosomal abnormality was detected in 28 cases (2.8% of all cases, 5.7% of the couples) most of which (92.9%) were structural abnormalities. All of the structural abnormalities were balanced chromosomal translocations. Chromosomal analysis performed from the abortion materials detected a major chromosomal abnormality in 31.9% of the cases. The most frequently observed alteration in the hereditary thrombophilia genes was heterozygote mutation for the MTHFR C677T polymorphisms (n=55). Balanced translocations are the most commonly detected chromosomal abnormalities in couples being evaluated for recurrent pregnancy loss and these patients are the best candidates for offering prenatal genetic diagnosis by the help of which there is a possibility of obtaining a better reproductive outcome.

  6. DTI-measured white matter abnormalities in adolescents with Conduct Disorder

    PubMed Central

    Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

    2013-01-01

    Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter

  7. Spine abnormalities depicted by magnetic resonance imaging in adolescent rowers.

    PubMed

    Maurer, Marvin; Soder, Ricardo Bernardi; Baldisserotto, Matteo

    2011-02-01

    Most lesions of the spine of athletes, which often are detected incidentally, do not cause important symptoms or make the athletes discontinue their physical activities. To better understand the significance of these lesions, new imaging studies have been conducted with asymptomatic athletes in several sports, aiming to detect potentially deleterious and disabling abnormalities. To compare the magnetic resonance imaging (MRI) lumbar spine findings in a group of asymptomatic adolescent rowers and in a control group of adolescents matched according to age and sex who do not practice any regular physical activity. Cohort study (prevalence); Level of evidence, 3. Our study evaluated 44 asymptomatic adolescent boys distributed in 2 groups of 22 rowers and 22 control subjects. All the examinations were performed using a 0.35-T open-field MRI unit and evaluated by 2 experienced radiologists blinded to the study groups. Each MRI scan was analyzed for the presence of disc degeneration/desiccation, herniated or bulging disc, pars interarticularis stress reaction, and spondylolysis. The Student t test and the Fisher exact test were used for statistical analyses. Nine rowers (40.9%) had at least 1 abnormality detected by MRI in the lumbar spine, whereas only 2 participants (9.1%) in the control group had at least 1 MRI abnormality (P = .03). Seven disc changes (31.8%) and 6 pars abnormalities (27.3%) were found in the group of elite rowers. In the control group, 3 disc changes (13.6%) and no pars abnormalities were found in the MR scans. The comparison between groups showed statistically significant differences in stress reaction of the pars articularis. Disc disease and pars interarticularis stress reaction are prevalent abnormalities of the lumbar spine of high-performance rowers.

  8. A Case of ADHD and a Major Y Chromosome Abnormality

    ERIC Educational Resources Information Center

    Mulligan, Aisling; Gill, Michael; Fitzgerald, Michael

    2008-01-01

    Background: ADHD is a common, heritable disorder of childhood. Sex chromosome abnormalities are relatively rare conditions that are sometimes associated with behavioral disorders. Method: The authors present a male child with ADHD and a major de-novo Y chromosome abnormality consisting of deletion of the long arm and duplication of the short arm.…

  9. Abnormalities of hybrid grouper (Epinephelus fuscoguttatus x Epinephelus lanceolatus) in Situbondo

    NASA Astrophysics Data System (ADS)

    Triastuti, J.; Pursetyo, K. T.; Monica, A.; Lutfiyah, L.; Budi, D. S.

    2018-04-01

    Grouper is one of consumption fish which is demanded excessively by local consumers and foreign consumers. Hybridization of grouper has been performed considerably that produce the good genetic quality of hybrid variants. One of grouper fish which has good genetic in its growth is kertang grouper fish. Nowadays many hatcheries performing hybridization between kertang grouper fish and tiger grouper fish, however observation of the hybrid abnormality has not been performed yet. Abnormality is able to increase since genetic causes, so that observation of abnormality occurrence in cantang hybrid grouper fish in Situbondo, JawaTimur, Indonesia in May – July in 3 times grading of juvenile stadia was performed. Results showed abnormalities were observed on mouth and operculum, branched of neural arch, fusion of neural arch, fusion of posterior truncus vertebrae, fusion of caudal vertebrae, fusion of anterior truncus vertebrae.

  10. LIPID ABNORMALITIES AND LIPID-BASED REPAIR STRATEGIES IN ATOPIC DERMATITIS

    PubMed Central

    Elias, Peter M.

    2013-01-01

    Prior studies have revealed the key roles played by Th1/Th2 cell dysregulation, IgE production, mast cell hyperactivity, and dendritic cell signaling in the evolution of the chronic, pruritic, inflammatory dermatosis that characterizes atopic dermatitis (AD). We review here increasing evidence that the inflammation in AD results primarily from inherited abnormalities in epidermal structural and enzymatic proteins that impact permeability barrier function. We also will show that the barrier defect can be attributed to a paracellular abnormality due to a variety of abnormalities in lipid composition, transport and extracellular organization. Accordingly, we also review the therapeutic implications of this emerging pathogenic paradigm, including several current and potentially novel, lipid-based approaches to corrective therapy. PMID:24128970

  11. Neural mechanisms of oculomotor abnormalities in the infantile strabismus syndrome.

    PubMed

    Walton, Mark M G; Pallus, Adam; Fleuriet, Jérome; Mustari, Michael J; Tarczy-Hornoch, Kristina

    2017-07-01

    Infantile strabismus is characterized by numerous visual and oculomotor abnormalities. Recently nonhuman primate models of infantile strabismus have been established, with characteristics that closely match those observed in human patients. This has made it possible to study the neural basis for visual and oculomotor symptoms in infantile strabismus. In this review, we consider the available evidence for neural abnormalities in structures related to oculomotor pathways ranging from visual cortex to oculomotor nuclei. These studies provide compelling evidence that a disturbance of binocular vision during a sensitive period early in life, whatever the cause, results in a cascade of abnormalities through numerous brain areas involved in visual functions and eye movements. Copyright © 2017 the American Physiological Society.

  12. Fetal karyotyping for chromosome abnormalities after an unexplained elevated maternal serum alpha-fetoprotein screening.

    PubMed

    Feuchtbaum, L B; Cunningham, G; Waller, D K; Lustig, L S; Tompkinson, D G; Hook, E B

    1995-08-01

    To study the chromosome abnormality rate among women with elevated levels of maternal serum alpha-fetoprotein (MSAFP) and the types of chromosome abnormalities in this population, and to compare this rate with reports in the literature and the rate observed in the general population. We studied 8097 women who chose to undergo amniocentesis and fetal karyotyping after having an elevated MSAFP test of 2.5 multiples of the median (MOM) or higher. All abnormal karyotypes were reviewed and grouped according to whether the elevated MSAFP value could be explained by a ventral wall or neural tube defect. The overall chromosome abnormality rate was 13.83 per 1000 amniocenteses. The rate in the "unexplained" group was 10.92 per 1000 amniocenteses. Just over half (53%) of the abnormal karyotypes were autosomal anomalies, and 47% were sex chromosome abnormalities. The autosomal aneuploidies observed most frequently were triploidy and trisomy 13. The sex chromosome abnormalities observed most frequently were the XXY and XYY karyotypes. Women who have unexplained elevated MSAFP values of 2.5 MOM or greater have a twofold increase in the rate of chromosome abnormalities in their fetuses compared with the general population (P < or = .001). This rate is consistent with other studies that used a 2.5 MOM cutoff. Studies that used a 2.0 MOM cutoff have reported chromosome abnormality rates that do not vary from general population estimates.

  13. Predictors of electrocardiographic abnormalities in type 1 Diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

    PubMed

    O'Neal, Wesley T; Lee, Kristine E; Soliman, Elsayed Z; Klein, Ronald; Klein, Barbara E K

    2017-03-01

    To determine the incidence and determinants of developing abnormalities on the 12-lead electrocardiogram (ECG) in persons with type 1 diabetes. We evaluated the distribution of ECG abnormalities and risk factors for developing new abnormalities in 266 (mean age = 44 years ± 9.0; 50 % female) people with type 1 diabetes from the Wisconsin Epidemiologic Study of Diabetic Retinopathy. This analysis included participants with complete ECG data from study visit 5 (2000-2001) and follow-up ECGs from study visit 7 (2012-2014). ECG abnormalities were classified as major and minor according to Minnesota Code Classification. At baseline, 94 (35 %) participants had at least one ECG abnormality, including 13 major ECG abnormalities. At follow-up, 117 (44 %) participants developed at least one new ECG abnormality, including 35 new major ECG abnormalities. In a multivariable logistic regression model, older age (per 5-year increase: OR = 1.31, 95 % CI = 1.08, 1.60) was associated with the development of at least one new ECG abnormality, while serum HDL cholesterol (per 10-unit increase: OR = 0.98, 95 % CI = 0.96, 1.00) was protective against developing new ECG abnormalities. The development of new ECG abnormalities is common in type 1 diabetes. Older age and HDL cholesterol are independent risk factors for developing new ECG abnormalities. Further research is needed to determine whether routine ECG screening is indicated in people with type 1 diabetes to identify those with underlying subclinical coronary heart disease.

  14. Relationship Between Pelvic Organ Prolapse and Non-Human Papillomavirus Pap Smear Abnormalities.

    PubMed

    Menhaji, Kimia; Harvie, Heidi S; Cheston, Emily; Levin, Pamela J; Arya, Lily A; Andy, Uduak U

    2017-07-13

    The aim of this study was to determine the association between pelvic organ prolapse (POP) and non-human papillomavirus (HPV) Papanicolaou (Pap) smear abnormalities. This was a retrospective cohort study of women aged 40 to 70 years who presented for consultation at our institution between 2010 and 2015 and had results of a Pap smear and HPV test available within 5 years of their visit. We extracted demographic information, medical and social history, Pap smear, and HPV results from the electronic medical record. Associations between the presence of POP and non-HPV Pap smear abnormalities were estimated using univariable and multivariable analyses. We reviewed 1590 charts and excluded 980 women, leaving 610 women in the study: 183 with POP and 427 without POP. Women with POP were significantly older (58.2 ± 7.2 vs 55.6 ± 6.6, P < 0.01) and more likely to have a remote (>10 year) history of abnormal Pap smear (24.0% vs 14.8%, P < 0.01). The rate of non-HPV-associated abnormal Pap smears was higher in the POP group than in the non-POP group (12/183 [6.6%] vs 12/427 [2.8%], P = 0.029). In the POP group, the rate of non-HPV Pap smear abnormality was significantly associated with increasing prolapse stage (stage 1: 0/16 [0%], stage 2: 5/77 [6.5%], stage 3: 3/73 [4.1%], stage 4: 4/17 [23.5%]; P = 0.02). After controlling for age and remote history of abnormal Pap smear, the odds ratio for non-HPV Pap smear abnormalities in the POP group remained significant (2.49; 95% confidence interval, 1.08-5.79). Human papillomavirus-negative Pap smear abnormalities may be related to POP. Our findings have important implications for surgeons seeking to leave the cervix in situ in women with POP.

  15. Abnormal fatty acids in Canadian children with autism.

    PubMed

    Jory, Joan

    2016-04-01

    Fatty acids are critical for pediatric neurodevelopment and are abnormal in autism, although prior studies have demonstrated conflicting results and methodological differences. To our knowledge, there are no published data on fatty acid in Canadian children with autism. The aim of this study was to investigate red blood cell and serum fatty acid status to identify whether abnormalities exist in Canadian children with autism, and to enhance future cross-study comparison. Eleven Canadian children with autism (3 girls, 8 boys; age 3.05 ± 0.79 y) and 15 controls (9 girls, 6 boys; age 3.87 ± 1.06 y) met inclusion criteria, which included prior Diagnostic and Statistical Manual diagnosis of autism spectrum disorder, no recent medication or supplements, no specialty diets, and no recent illness. The children with autism demonstrated lower red blood cell docosahexaenoic acid (P < 0.0003), eicosapentaenoic acid (P < 0.03), arachidonic acid (P < 0.002), and ω-3/ω-6 ratios (P < 0.001). They also demonstrated lower serum docosahexaenoic acid (P < 0.02), arachidonic acid (P < 0.05), and linoleic acid (P < 0.02) levels. Fatty acids in both serum and red blood cells were abnormal in this small group of Canadian children with autism than in controls, underlining a need for larger age- and sex-matched investigations in this community. A potential role for fatty acid abnormalities within the complex epigenetic etiology of autism is proposed in relation to emerging understanding of relationships between cobalamin metabolism, gut microbiota, and propionic acid production. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Radiographic Abnormalities in the Feet of Diabetic Patients with Neuropathy and Foot Ulceration.

    PubMed

    Viswanathan, Vijay; Kumpatla, Satyavani; Rao, V Narayan

    2014-11-01

    People with diabetic neuropathy are frequently prone to several bone and joint abnormalities. Simple radiographic findings have been proven to be quite useful in the detection of such abnormalities, which might be helpful not only for early diagnosis but also in following the course of diabetes through stages of reconstruction of the ulcerated foot.The present study was designed to identify the common foot abnormalities in south Indian diabetic subjects with and without neuropathy using radiographic imaging. About 150 (M:F 94:56) subjects with type 2 diabetes were categorised into three groups: Group I (50 diabetic patients), Group II (50 patients with neuropathy), and Group III (50 diabetic patients with both neuropathy and foot ulceration). Demographic details, duration of diabetes and HbA1c values were recorded. Vibration perception threshold was measured for assessment of neuropathy. Bone and joint abnormalities in the feet and legs of the study subjects were identified using standardised dorsi-plantar and lateral weight-bearing radiographs. Radiographic findings of the study subjects revealed that those with both neuropathy and foot ulceration and a longer duration of diabetes had more number of bone and joint abnormalities. Subjects with neuropathy alone also showed presence of several abnormalities, including periosteal reaction, osteopenia, and Charcot changes. The present findings highlight the impact of neuropathy and duration of diabetes on the development of foot abnormalities in subjects with diabetes. Using radiographic imaging can help in early identification of abnormalities and better management of the diabetic foot.

  17. Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study

    PubMed Central

    Walton, Kerry D.; Maillet, Emeline L.; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinás, Rodolfo R.

    2017-01-01

    1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5–8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5–4.5 Hz and 4.5–6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a

  18. Differential Modulation of Rhythmic Brain Activity in Healthy Adults by a T-Type Calcium Channel Blocker: An MEG Study.

    PubMed

    Walton, Kerry D; Maillet, Emeline L; Garcia, John; Cardozo, Timothy; Galatzer-Levy, Isaac; Llinás, Rodolfo R

    2017-01-01

    1-octanol is a therapeutic candidate for disorders involving the abnormal activation of the T-type calcium current since it blocks this current specifically. Such disorders include essential tremor and a group of neurological and psychiatric disorders resulting from thalamocortical dysrhythmia (TCD). For example, clinically, the observable phenotype in essential tremor is the tremor itself. The differential diagnostic of TCD is not based only on clinical signs and symptoms. Rather, TCD incorporates an electromagnetic biomarker, the presence of abnormal thalamocortical low frequency brain oscillations. The effect of 1-octanol on brain activity has not been tested. As a preliminary step to such a TCD study, we examined the short-term effects of a single dose of 1-octanol on resting brain activity in 32 healthy adults using magnetoencephalograpy. Visual inspection of baseline power spectra revealed that the subjects fell into those with strong low frequency activity (set 2, n = 11) and those without such activity, but dominated by an alpha peak (set 1, n = 22). Cross-validated linear discriminant analysis, using mean spectral density (MSD) in nine frequency bands as predictors, found overall that 82.5% of the subjects were classified as determined by visual inspection. The effect of 1-octanol on the MSD in narrow frequency bands differed between the two subject groups. In set 1 subjects the MSD increased in the 4.5-6.5Hz and 6.5-8.5 Hz bands. This was consistent with a widening of the alpha peak toward lower frequencies. In the set two subjects the MSD decrease in the 2.5-4.5 Hz and 4.5-6.5 Hz bands. This decreased power is consistent with the blocking effect of 1-octanol on T-type calcium channels. The subjects reported no adverse effects of the 1-octanol. Since stronger low frequency activity is characteristic of patients with TCD, 1-octanol and other T-type calcium channel blockers are good candidates for treatment of this group of disorders following a placebo

  19. Triple-phase bone image abnormalities in Lyme arthritis

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

    Brown, S.J.; Dadparvar, S.; Slizofski, W.J.

    1989-10-01

    Arthritis is a frequent manifestation of Lyme disease. Limited triple-phase Tc-99m MDP bone imaging of the wrists and hands with delayed whole-body images was performed in a patient with Lyme arthritis. This demonstrated abnormal joint uptake in the wrists and hands in all three phases, with increased activity seen in other affected joints on delayed whole-body images. These findings are nonspecific and have been previously described in a variety of rheumatologic conditions, but not in Lyme disease. Lyme disease should be considered in the differential diagnosis of articular and periarticular bone scan abnormalities.

  20. Abnormal Canine Bone Development Associated with Hypergravity Exposure

    NASA Technical Reports Server (NTRS)

    Morgan, J. P.; Fisher, G. L.; McNeill, K. L.; Oyama, J.

    1979-01-01

    Chronic centrifugation of 85- to 92-day-old Beagles at 2.0 x g and 2.6 x g for 26 weeks during the time of active skeletal growth caused skeletal abnormalities in the radius and the ulna of ten of 11 dogs. The pattern of change mimicked that found in naturally occurring and experimentally induced premature distal ulnar physeal closure or delayed growth at this physis. Minimal changes in bone density were detected by sensitive photon absorptiometric techniques. Skeletal abnormalities also were found in five of the six cage-control dogs, although the run-control dogs were radiographically normal.