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Sample records for aberrant neural activity

  1. Aberrant early visual neural activity and brain-behavior relationships in anorexia nervosa and body dysmorphic disorder

    PubMed Central

    Li, Wei; Lai, Tsz M.; Loo, Sandra K.; Strober, Michael; Mohammad-Rezazadeh, Iman; Khalsa, Sahib; Feusner, Jamie

    2015-01-01

    Background: Body dysmorphic disorder (BDD) and anorexia nervosa (AN) share the clinical symptom of disturbed body image, which may be a function of perceptual distortions. Previous studies suggest visual or visuospatial processing abnormalities may be contributory, but have been unable to discern whether these occur early or late in the visual processing stream. We used electroencephalography (EEG) and visual event related potentials (ERP) to investigate early perceptual neural activity associated with processing visual stimuli. Methods: We performed EEG on 20 AN, 20 BDD, 20 healthy controls, all unmedicated. In order to probe configural/holistic and detailed processing, participants viewed photographs of faces and houses that were unaltered or filtered to low or high spatial frequencies, respectively. We calculated the early ERP components P100 and N170, and compared amplitudes and latencies among groups. Results: P100 amplitudes were smaller in AN than BDD and healthy controls, regardless of spatial frequency or stimulus type (faces or houses). Similarly, N170 latencies were longer in AN than healthy controls, regardless of spatial frequency or stimulus type, with a similar pattern in BDD at trend level significance. N170 amplitudes were smaller in AN than controls for high and normal spatial frequency images, and smaller in BDD than controls for normal spatial frequency images, regardless of stimulus type. Poor insight correlated with lower N170 amplitudes for normal and low spatial frequency faces in the BDD group. Conclusions: Individuals with AN exhibit abnormal early visual system activity, consistent with reduced configural processing and enhanced detailed processing. This is evident regardless of whether the stimuli are appearance–or non-appearance-related, and thus may be a reflection of general, early perceptual abnormalities. As N170 amplitude could be a marker of structural encoding of faces, lower values may be associated with perceptual distortions

  2. Artificial neural network for the determination of Hubble Space Telescope aberration from stellar images

    NASA Technical Reports Server (NTRS)

    Barrett, Todd K.; Sandler, David G.

    1993-01-01

    An artificial-neural-network method, first developed for the measurement and control of atmospheric phase distortion, using stellar images, was used to estimate the optical aberration of the Hubble Space Telescope. A total of 26 estimates of distortion was obtained from 23 stellar images acquired at several secondary-mirror axial positions. The results were expressed as coefficients of eight orthogonal Zernike polynomials: focus through third-order spherical. For all modes other than spherical the measured aberration was small. The average spherical aberration of the estimates was -0.299 micron rms, which is in good agreement with predictions obtained when iterative phase-retrieval algorithms were used.

  3. Association of aberrant neural synchrony and altered GAD67 expression following exposure to maternal immune activation, a risk factor for schizophrenia

    PubMed Central

    Dickerson, D D; Overeem, K A; Wolff, A R; Williams, J M; Abraham, W C; Bilkey, D K

    2014-01-01

    A failure of integrative processes within the brain, mediated via altered GABAergic inhibition, may underlie several features of schizophrenia. The present study examined, therefore, whether maternal immune activation (MIA), a risk factor for schizophrenia, altered inhibitory markers in the hippocampus and medial prefrontal cortex (mPFC), while also altering electroencephalogram (EEG) coherence between these regions. Pregnant rats were treated with saline or polyinosinic:polycytidylic acid mid-gestation. EEG depth recordings were made from the dorsal and ventral hippocampus and mPFC of male adult offspring. Glutamic decarboxylase (GAD67) levels were separately assayed in these regions using western blot. GAD67 expression was also assessed within parvalbumin-positive cells in the dorsal and ventral hippocampus using immunofluorescence alongside stereological analysis of parvalbumin-positive cell numbers. EEG coherence was reduced between the dorsal hippocampus and mPFC, but not the ventral hippocampus and mPFC, in MIA animals. Western blot and immunofluorescence analyses revealed that GAD67 expression within parvalbumin-positive cells was also reduced in the dorsal hippocampus relative to ventral hippocampus in MIA animals when compared with controls. This reduction was observed in the absence of parvalbumin-positive neuronal loss. Overall, MIA produced a selective reduction in EEG coherence between the dorsal hippocampus and mPFC that was paralleled by a similarly specific reduction in GAD67 within parvalbumin-positive cells of the dorsal hippocampus. These results suggest a link between altered inhibitory mechanisms and synchrony and, therefore point to potential mechanisms via which a disruption in neurodevelopmental processes might lead to pathophysiology associated with schizophrenia. PMID:25072323

  4. Suppressors of hedgehog signaling: Linking aberrant development of neural progenitors and tumorigenesis.

    PubMed

    Di Marcotullio, Lucia; Ferretti, Elisabetta; De Smaele, Enrico; Screpanti, Isabella; Gulino, Alberto

    2006-12-01

    Subversion of signals that physiologically suppress Hedgehog pathway results in aberrant neural progenitor development and medulloblastoma, a malignancy of the cerebellum. The Hedgehog antagonist RENKCTD11 maps to chromosome 17p13.2 and is involved in the withdrawal of the Hedgehog signaling at the granule cell progenitor transition from the outer to the inner external germinal layers, thus promoting growth arrest and differentiation. Deletion of chromosome 17p, the most frequent genetic lesion observed in this tumor, is responsible for the loss of function of RENKCTD11, resulting in upregulated Hedgehog signaling and medulloblastoma. Persistence of signals that limit Hedgehog activity is also associated with malignancy. Hedgehog signaling- induced downregulation of ErbB4 receptor expression is attenuated in medulloblastoma subsets in which the extent of Hedgehog pathway activity is limited, thus favoring the accumulation of ErbB4 with imbalanced alternative splice CYT-1 isoform over the CYT-2. This is responsible for both Neuregulin ligand-induced CYT-1-dependent prosurvival activity and loss of CYT-2-mediated growth arrest. PMID:17308352

  5. Aberrant Neural Connectivity during Emotional Processing Associated with Posttraumatic Stress

    PubMed Central

    Sadeh, Naomi; Spielberg, Jeffrey M.; Warren, Stacie L.; Miller, Gregory A.; Heller, Wendy

    2014-01-01

    Given the complexity of the brain, characterizing relations among distributed brain regions is likely essential to describing the neural instantiation of posttraumatic stress symptoms. This study examined patterns of functional connectivity among key brain regions implicated in the pathophysiology of posttraumatic stress disorder (PTSD) in 35 trauma-exposed adults using an emotion-word Stroop task. PTSD symptom severity (particularly hyperarousal symptoms) moderated amygdala-mPFC coupling during the processing of unpleasant words, and this moderation correlated positively with reported real-world impairment and amygdala reactivity. Reexperiencing severity moderated hippocampus-insula coupling during pleasant and unpleasant words. Results provide evidence that PTSD symptoms differentially moderate functional coupling during emotional interference and underscore the importance of examining network connectivity in research on PTSD. They suggest that hyperarousal is associated with negative mPFC-amygdala coupling and that reexperiencing is associated with altered insula-hippocampus function, patterns of connectivity that may represent separable indicators of dysfunctional inhibitory control during affective processing. PMID:25419500

  6. Active Optical Control of Quasi-Static Aberrations for ATST

    NASA Astrophysics Data System (ADS)

    Johnson, L. C.; Upton, R.; Rimmele, T. R.; Hubbard, R.; Barden, S. C.

    2012-12-01

    The Advanced Technology Solar Telescope (ATST) requires active control of quasi-static telescope aberrations in order to achieve the image quality set by its science requirements. Four active mirrors will be used to compensate for optical misalignments induced by changing gravitational forces and thermal gradients. These misalignments manifest themselves primarily as low-order wavefront aberrations that will be measured by a Shack-Hartmann wavefront sensor. When operating in closed-loop with the wavefront sensor, the active optics control algorithm uses a linear least-squares reconstructor incorporating force constraints to limit force applied to the primary mirror while also incorporating a neutral-point constraint on the secondary mirror to limit pointing errors. The resulting system compensates for astigmatism and defocus with rigid-body motion of the secondary mirror and higher-order aberrations with primary mirror bending modes. We demonstrate this reconstruction method and present simulation results that apply the active optics correction to aberrations generated by finite-element modeling of thermal and gravitational effects over a typical day of ATST operation. Quasi-static wavefront errors are corrected to within limits set by wavefront sensor noise in all cases with very little force applied to the primary mirror surface and minimal pointing correction needed.

  7. Technologies for imaging neural activity in large volumes.

    PubMed

    Ji, Na; Freeman, Jeremy; Smith, Spencer L

    2016-08-26

    Neural circuitry has evolved to form distributed networks that act dynamically across large volumes. Conventional microscopy collects data from individual planes and cannot sample circuitry across large volumes at the temporal resolution relevant to neural circuit function and behaviors. Here we review emerging technologies for rapid volume imaging of neural circuitry. We focus on two critical challenges: the inertia of optical systems, which limits image speed, and aberrations, which restrict the image volume. Optical sampling time must be long enough to ensure high-fidelity measurements, but optimized sampling strategies and point-spread function engineering can facilitate rapid volume imaging of neural activity within this constraint. We also discuss new computational strategies for processing and analyzing volume imaging data of increasing size and complexity. Together, optical and computational advances are providing a broader view of neural circuit dynamics and helping elucidate how brain regions work in concert to support behavior. PMID:27571194

  8. Aberrant Neural Stem Cell Proliferation and Increased Adult Neurogenesis in Mice Lacking Chromatin Protein HMGB2

    PubMed Central

    Reddy, Avanish S.; Maletic-Savatic, Mirjana; Aguirre, Adan; Tsirka, Stella E.

    2013-01-01

    Neural stem and progenitor cells (NSCs/NPCs) are distinct groups of cells found in the mammalian central nervous system (CNS). Previously we determined that members of the High Mobility Group (HMG) B family of chromatin structural proteins modulate NSC proliferation and self-renewal. Among them HMGB2 was found to be dynamically expressed in proliferating and differentiating NSCs, suggesting that it may regulate NSC maintenance. We report now that Hmgb2−/− mice exhibit SVZ hyperproliferation, increased numbers of SVZ NSCs, and a trend towards aberrant increases in newly born neurons in the olfactory bulb (OB) granule cell layer. Increases in the levels of the transcription factor p21 and the Neural cell adhesion molecule (NCAM), along with down-regulation of the transcription/pluripotency factor Oct4 in the Hmgb2−/− SVZ point to a possible pathway for this increased proliferation/differentiation. Our findings suggest that HMGB2 functions as a modulator of neurogenesis in young adult mice through regulation of NSC proliferation, and identify a potential target via which CNS repair could be amplified following trauma or disease-based neuronal degeneration. PMID:24391977

  9. Active Correction of Aberrations of Low-Quality Telescope Optics

    NASA Technical Reports Server (NTRS)

    Hemmati, Hamid; Chen, Yijian

    2007-01-01

    A system of active optics that includes a wavefront sensor and a deformable mirror has been demonstrated to be an effective means of partly correcting wavefront aberrations introduced by fixed optics (lenses and mirrors) in telescopes. It is envisioned that after further development, active optics would be used to reduce wavefront aberrations of about one wave or less in telescopes having aperture diameters of the order of meters or tens of meters. Although this remaining amount of aberration would be considered excessive in scientific applications in which diffraction-limited performance is required, it would be acceptable for free-space optical- communication applications at wavelengths of the order of 1 m. To prevent misunderstanding, it is important to state the following: The technological discipline of active optics, in which the primary or secondary mirror of a telescope is directly and dynamically tilted, distorted, and/or otherwise varied to reduce wavefront aberrations, has existed for decades. The term active optics does not necessarily mean the same thing as does adaptive optics, even though active optics and adaptive optics are related. The term "adaptive optics" is often used to refer to wavefront correction at speeds characterized by frequencies ranging up to between hundreds of hertz and several kilohertz high enough to enable mitigation of adverse effects of fluctuations in atmospheric refraction upon propagation of light beams. The term active optics usually appears in reference to wavefront correction at significantly lower speeds, characterized by times ranging from about 1 second to as long as minutes. Hence, the novelty of the present development lies, not in the basic concept of active or adaptive optics, but in the envisioned application of active optics in conjunction with a deformable mirror to achieve acceptably small wavefront errors in free-space optical communication systems that include multi-meter-diameter telescope mirrors that are

  10. Aberrant Activity in Degenerated Retinas Revealed by Electrical Imaging

    PubMed Central

    Zeck, Günther

    2016-01-01

    In this review, I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL) of rod-degenerated (rd) mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between spiking activity originating from retinal ganglion cells (RGCs) and local field potentials (LFPs) reflecting strong trans-membrane currents within the GCL. RGCs in rd retinas show increased and rhythmic spiking compared to age-matched wild-type retinas. Fundamental spiking frequencies range from 5 to 15 Hz in various mouse models. The rhythmic RGC spiking is driven by a presynaptic network comprising AII amacrine and bipolar cells. In the healthy retina this rhythm-generating circuit is inhibited by photoreceptor input. A unique physiological feature of rd retinas is rhythmic LFP manifested as spatially-restricted low-frequency (5–15 Hz) voltage changes. Their spatiotemporal characterization revealed propagation and correlation with RGC spiking. LFPs rely on gap-junctional coupling and are shaped by glycinergic and by GABAergic transmission. The aberrant RGC spiking and LFPs provide a simple readout of the functionality of the remaining retinal circuitry which can be used in the development of improved vision restoration strategies. PMID:26903810

  11. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    PubMed Central

    Chen, Yu-Chen; Zhang, Jian; Li, Xiao-Wei; Xia, Wenqing; Feng, Xu; Gao, Bo; Ju, Sheng-Hong; Wang, Jian; Salvi, Richard; Teng, Gao-Jun

    2014-01-01

    Objective The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. Materials and methods A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. Results Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. Conclusions The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients. PMID:25379434

  12. Male veterans with PTSD exhibit aberrant neural dynamics during working memory processing: an MEG study

    PubMed Central

    McDermott, Timothy J.; Badura-Brack, Amy S.; Becker, Katherine M.; Ryan, Tara J.; Khanna, Maya M.; Heinrichs-Graham, Elizabeth; Wilson, Tony W.

    2016-01-01

    Background Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory. In this study, we examined the neural dynamics of working memory processing in veterans with PTSD and a matched healthy control sample using magnetoencephalography (MEG). Methods Our sample of recent combat veterans with PTSD and demographically matched participants without PTSD completed a working memory task during a 306-sensor MEG recording. The MEG data were preprocessed and transformed into the time-frequency domain. Significant oscillatory brain responses were imaged using a beamforming approach to identify spatiotemporal dynamics. Results Fifty-one men were included in our analyses: 27 combat veterans with PTSD and 24 controls. Across all participants, a dynamic wave of neural activity spread from posterior visual cortices to left frontotemporal regions during encoding, consistent with a verbal working memory task, and was sustained throughout maintenance. Differences related to PTSD emerged during early encoding, with patients exhibiting stronger α oscillatory responses than controls in the right inferior frontal gyrus (IFG). Differences spread to the right supramarginal and temporal cortices during later encoding where, along with the right IFG, they persisted throughout the maintenance period. Limitations This study focused on men with combat-related PTSD using a verbal working memory task. Future studies should evaluate women and the impact of various traumatic experiences using diverse tasks. Conclusion Posttraumatic stress disorder is associated with neurophysiological abnormalities during working memory encoding and maintenance. Veterans with PTSD engaged a bilateral network, including the inferior prefrontal cortices and supramarginal gyri. Right hemispheric neural activity likely reflects compensatory processing, as veterans with PTSD work to maintain accurate performance despite known cognitive deficits

  13. Polarization aberrations in the solar activity measurements experiments (SAMEX) solar vector magnetograph

    NASA Technical Reports Server (NTRS)

    Mcguire, James P., Jr.; Chipman, Russell A.

    1989-01-01

    An optical design and polarization analysis of the Air Force/NASA Solar Activity Measurements Experiments solar vector magnetograph optical system is performed. Polarization aberration theory demonstrates that conventional telescope coating designs introduce unacceptably high levels of polarization aberrations into the optical system. Several ultralow polarization mirror and lens coatings designs for this instrument are discussed. Balancing of polarization aberrations at different surfaces is demonstrated.

  14. Removing static aberrations from the active optics system of a wide-field telescope.

    PubMed

    Schipani, Pietro; Noethe, Lothar; Arcidiacono, Carmelo; Argomedo, Javier; Dall'Ora, Massimo; D'Orsi, Sergio; Farinato, Jacopo; Magrin, Demetrio; Marty, Laurent; Ragazzoni, Roberto; Umbriaco, Gabriele

    2012-07-01

    The wavefront sensor in active and adaptive telescopes is usually not in the optical path toward the scientific detector. It may generate additional wavefront aberrations, which have to be separated from the errors due to the telescope optics. The aberrations that are not rotationally symmetric can be disentangled from the telescope aberrations by a series of measurements taken in the center of the field, with the wavefront sensor at different orientation angles with respect to the focal plane. This method has been applied at the VLT Survey Telescope on the ESO Paranal observatory. PMID:22751401

  15. Actively compensation of low order aberrations by refractive shaping system for high power slab lasers

    NASA Astrophysics Data System (ADS)

    Xue, Zheng-wei; Guo, Ya-ding; Chen, Zhong-zheng; Li, Shuai; Xu, Yi-ting; Xu, Jian; Wang, Bao-shan; Gong, Ke-ling; Gao, Hong-wei; Bo, Yong; Peng, Qin-jun; Cui, Da-fu; Xu, Zu-yan

    2015-12-01

    We present a compact refractive shaping system for actively compensating low order aberrations of high power slab lasers. The shaping system includes three spherical lenses and two cylindrical lenses. Both theoretical and experimental investigations were performed to evaluate the compensation capability of the refractive shaping system. For a typical input beam with large low order aberrations of peak-to-valley (PV)=66.10λ and root-mean-square (RMS)=16.05λ, adjusting the distance between lenses, the wavefront aberrations are reduced to PV=0.48λ, RMS=0.10λ for the theoretical simulation and PV=0.50λ, RMS=0.11λ for the experimental result, respectively. It indicates that the main low order aberrations of defocus and 0° astigmatism can be significantly compensated by actively adjusting the distance between lenses and the experimental result agree well with the theoretical simulation.

  16. Associative memory model with spontaneous neural activity

    NASA Astrophysics Data System (ADS)

    Kurikawa, Tomoki; Kaneko, Kunihiko

    2012-05-01

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

  17. Striatal Activity is Associated with Deficits of Cognitive Control and Aberrant Salience for Patients with Schizophrenia

    PubMed Central

    Ceaser, Alan E.; Barch, Deanna M.

    2016-01-01

    A recent meta-analysis has shown that a large dopamine abnormality exists in the striatum when comparing patients with schizophrenia and controls, and this abnormality is thought to contribute to aberrant salience assignment (or a misattribution of relevance to irrelevant stimuli). This abnormality may also disrupt striatal contributions to cognitive control processing. We examined the relationship between striatal involvement in cognition and aberrant salience symptoms using a task of cognitive control that involves updating, interference control, and simple maintenance. The current study included a sample of 22 patients with schizophrenia and 20 healthy controls and used a slow event-related fMRI design. We predicted that (1) aberrant salience symptoms would be greater for patient's, (2) patients would demonstrate increased errors during interference control trials, given that patients may be inappropriately assigning salience to distracters, and (3) striatal activity during those errors would be correlated with aberrant salience symptoms. We found a trend toward a significant difference between patients and controls on aberrant salience symptoms, and a significant difference between groups on select task conditions. During interference control trials, patients were more likely to inappropriately encode distracters. For patients, both prefrontal and striatal activity was significantly greater when patients inappropriately identified the distracter as correct compared to activity during distracter rejection. During updating, patient prefrontal and striatal activity was significantly lower for incorrect than correct updating trials. Finally, as predicted, for patients the increase of activity during incorrect distracter trials was positively correlated with aberrant salience symptoms, but only for the striatal region. These relationships may have implications for treatments that improve cognitive function and reduce symptom expression. PMID:26869912

  18. Phytochemicals attenuating aberrant activation of ß-catenin in cancer cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/ß-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of ß-catenin, a key causative step in a broad spectrum of c...

  19. Aberrant regional neural fluctuations and functional connectivity in generalized anxiety disorder revealed by resting-state functional magnetic resonance imaging.

    PubMed

    Wang, Wei; Hou, Jingming; Qian, Shaowen; Liu, Kai; Li, Bo; Li, Min; Peng, Zhaohui; Xin, Kuolin; Sun, Gang

    2016-06-15

    The purpose of this study was to investigate the neural activity and functional connectivity in generalized anxiety disorder (GAD) during resting state, and how these alterations correlate to patients' symptoms. Twenty-eight GAD patients and 28 matched healthy controls underwent resting-state functional magnetic resonance (fMRI) scans. Amplitude of low-frequency fluctuation (ALFF) and seed-based resting-state functional connectivity (RSFC) were computed to explore regional activity and functional integration, and were compared between the two groups using the voxel-based two-sample t test. Pearson's correlation analyses were performed to examine the neural relationships with demographics and clinical symptoms scores. Compared to controls, GAD patients showed functional abnormalities: higher ALFF in the bilateral dorsomedial prefrontal cortex, bilateral dorsolateral prefrontal cortex and left precuneus/posterior cingulate cortex; lower connectivity in prefrontal gyrus; lower in prefrontal-limbic and cingulate RSFC and higher prefrontal-hippocampus RSFC were correlated with clinical symptoms severity, but these associations were unable to withstand correction for multiple testing. These findings may help facilitate further understanding of the potential neural substrate of GAD. PMID:27163197

  20. Aberrant Neural Function during Emotion Attribution in Female Subjects with Fragile X Syndrome

    ERIC Educational Resources Information Center

    Hagan, Cindy C.; Hoeft, Fumiko; Mackey, Allyson; Mobbs, Dean; Reiss, Allan L.

    2008-01-01

    The neurobiological systems which underlie emotion attribution among female patients with Fragile X (FraX) syndrome are examined. Results show that the emotion circuit which regulates responses to facial stimuli is potentially disrupted among female subjects with FraX syndrome. Anterior cingulate cortex activity in female subjects with FraX…

  1. Information transmission in oscillatory neural activity.

    PubMed

    Koepsell, Kilian; Sommer, Friedrich T

    2008-11-01

    Periodic neural activity not locked to the stimulus or to motor responses is usually ignored. Here, we present new tools for modeling and quantifying the information transmission based on periodic neural activity that occurs with quasi-random phase relative to the stimulus. We propose a model to reproduce characteristic features of oscillatory spike trains, such as histograms of inter-spike intervals and phase locking of spikes to an oscillatory influence. The proposed model is based on an inhomogeneous Gamma process governed by a density function that is a product of the usual stimulus-dependent rate and a quasi-periodic function. Further, we present an analysis method generalizing the direct method (Rieke et al. in Spikes: exploring the neural code. MIT Press, Cambridge, 1999; Brenner et al. in Neural Comput 12(7):1531-1552, 2000) to assess the information content in such data. We demonstrate these tools on recordings from relay cells in the lateral geniculate nucleus of the cat. PMID:18985377

  2. Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.

    PubMed

    Yousuf, Mohammad A; Tan, Chunfeng; Torres-Altoro, Melissa I; Lu, Fang-Min; Plautz, Erik; Zhang, Shanrong; Takahashi, Masaya; Hernandez, Adan; Kernie, Steven G; Plattner, Florian; Bibb, James A

    2016-07-01

    Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. Aberrant activation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neuronal injury and neurodegeneration. Cdk5 is a neuronal protein kinase activated via interaction with its cofactor p35 that regulates numerous neuronal functions, including synaptic remodeling and cognition. However, conversion of p35 to p25 via Ca(2+) -dependent activation of calpain results in an aberrantly active Cdk5/p25 complex that is associated with neuronal damage and cell death. Here, we show that mice subjected to controlled cortical impact (CCI), a well-established experimental TBI model, exhibit increased p25 levels and consistently elevated Cdk5-dependent phosphorylation of microtubule-associated protein tau and retinoblastoma (Rb) protein in hippocampal lysates. Moreover, CCI-induced neuroinflammation as indicated by increased astrocytic activation and number of reactive microglia. Brain-wide conditional Cdk5 knockout mice (Cdk5 cKO) subjected to CCI exhibited significantly reduced edema, ventricular dilation, and injury area. Finally, neurophysiological recordings revealed that CCI attenuated excitatory post-synaptic potential field responses in the hippocampal CA3-CA1 pathway 24 h after injury. This neurophysiological deficit was attenuated in Cdk5 cKO mice. Thus, TBI induces increased levels of p25 generation and aberrant Cdk5 activity, which contributes to pathophysiological processes underlying TBI progression. Hence, selectively preventing aberrant Cdk5 activity may be an effective acute strategy to improve recovery from TBI. Traumatic brain injury (TBI) increases astrogliosis and microglial activation

  3. Block of gap junctions eliminates aberrant activity and restores light responses during retinal degeneration.

    PubMed

    Toychiev, Abduqodir H; Ivanova, Elena; Yee, Christopher W; Sagdullaev, Botir T

    2013-08-28

    Retinal degeneration leads to progressive photoreceptor cell death, resulting in vision loss. Subsequently, inner retinal neurons develop aberrant synaptic activity, compounding visual impairment. In retinal ganglion cells, light responses driven by surviving photoreceptors are obscured by elevated levels of aberrant spiking activity. Here, we demonstrate in rd10 mice that targeting disruptive neuronal circuitry with a gap junction antagonist can significantly reduce excessive spiking. This treatment increases the sensitivity of the degenerated retina to light stimuli driven by residual photoreceptors. Additionally, this enhances signal transmission from inner retinal neurons to ganglion cells, potentially allowing the retinal network to preserve the fidelity of signals either from prosthetic electronic devices, or from cells optogenetically modified to transduce light. Thus, targeting maladaptive changes to the retina allows for treatments to use existing neuronal tissue to restore light sensitivity, and to augment existing strategies to replace lost photoreceptors. PMID:23986234

  4. Neural activation during response competition

    NASA Technical Reports Server (NTRS)

    Hazeltine, E.; Poldrack, R.; Gabrieli, J. D.

    2000-01-01

    The flanker task, introduced by Eriksen and Eriksen [Eriksen, B. A., & Eriksen, C. W. (1974). Effects of noise letters upon the identification of a target letter in a nonsearch task. Perception & Psychophysics, 16, 143--149], provides a means to selectively manipulate the presence or absence of response competition while keeping other task demands constant. We measured brain activity using functional magnetic resonance imaging (fMRI) during performance of the flanker task. In accordance with previous behavioral studies, trials in which the flanking stimuli indicated a different response than the central stimulus were performed significantly more slowly than trials in which all the stimuli indicated the same response. This reaction time effect was accompanied by increases in activity in four regions: the right ventrolateral prefrontal cortex, the supplementary motor area, the left superior parietal lobe, and the left anterior parietal cortex. The increases were not due to changes in stimulus complexity or the need to overcome previously learned associations between stimuli and responses. Correspondences between this study and other experiments manipulating response interference suggest that the frontal foci may be related to response inhibition processes whereas the posterior foci may be related to the activation of representations of the inappropriate responses.

  5. Neural predictive control for active buffet alleviation

    NASA Astrophysics Data System (ADS)

    Pado, Lawrence E.; Lichtenwalner, Peter F.; Liguore, Salvatore L.; Drouin, Donald

    1998-06-01

    The adaptive neural control of aeroelastic response (ANCAR) and the affordable loads and dynamics independent research and development (IRAD) programs at the Boeing Company jointly examined using neural network based active control technology for alleviating undesirable vibration and aeroelastic response in a scale model aircraft vertical tail. The potential benefits of adaptive control includes reducing aeroelastic response associated with buffet and atmospheric turbulence, increasing flutter margins, and reducing response associated with nonlinear phenomenon like limit cycle oscillations. By reducing vibration levels and thus loads, aircraft structures can have lower acquisition cost, reduced maintenance, and extended lifetimes. Wind tunnel tests were undertaken on a rigid 15% scale aircraft in Boeing's mini-speed wind tunnel, which is used for testing at very low air speeds up to 80 mph. The model included a dynamically scaled flexible fail consisting of an aluminum spar with balsa wood cross sections with a hydraulically powered rudder. Neural predictive control was used to actuate the vertical tail rudder in response to strain gauge feedback to alleviate buffeting effects. First mode RMS strain reduction of 50% was achieved. The neural predictive control system was developed and implemented by the Boeing Company to provide an intelligent, adaptive control architecture for smart structures applications with automated synthesis, self-optimization, real-time adaptation, nonlinear control, and fault tolerance capabilities. It is designed to solve complex control problems though a process of automated synthesis, eliminating costly control design and surpassing it in many instances by accounting for real world non-linearities.

  6. Seismic active control by neural networks.

    SciTech Connect

    Tang, Y.

    1998-01-01

    A study on the application of artificial neural networks (ANNs) to activate structural control under seismic loads is carried out. The structure considered is a single-degree-of-freedom (SDF) system with an active bracing device. The control force is computed by a trained neural network. The feed-forward neural network architecture and an adaptive back-propagation training algorithm is used in the study. The neural net is trained to reproduce the function that represents the response-excitation relationship of the SDF system under seismic loads. The input-output training patterns are generated randomly. In the back-propagation training algorithm, the learning rate is determined by ensuring the decrease of the error function at each epoch. The computer program implemented is validated by solving the classification of the XOR problem. Then, the trained ANN is used to compute the control force according to the control strategy. If the control force exceeds the actuator's capacity limit, it is set equal to that limit. The concept of the control strategy employed herein is to apply the control force at every time step to cancel the system velocity induced at the preceding time step so that the gradual rhythmic buildup of the response is destroyed. The ground motions considered in the numerical example are the 1940 El Centro earthquake and the 1979 Imperial Valley earthquake in California. The system responses with and without the control are calculated and compared. The feasibility and potential of applying ANNs to seismic active control is asserted by the promising results obtained from the numerical examples studied.

  7. Modeling neural activity with cumulative damage distributions.

    PubMed

    Leiva, Víctor; Tejo, Mauricio; Guiraud, Pierre; Schmachtenberg, Oliver; Orio, Patricio; Marmolejo-Ramos, Fernando

    2015-10-01

    Neurons transmit information as action potentials or spikes. Due to the inherent randomness of the inter-spike intervals (ISIs), probabilistic models are often used for their description. Cumulative damage (CD) distributions are a family of probabilistic models that has been widely considered for describing time-related cumulative processes. This family allows us to consider certain deterministic principles for modeling ISIs from a probabilistic viewpoint and to link its parameters to values with biological interpretation. The CD family includes the Birnbaum-Saunders and inverse Gaussian distributions, which possess distinctive properties and theoretical arguments useful for ISI description. We expand the use of CD distributions to the modeling of neural spiking behavior, mainly by testing the suitability of the Birnbaum-Saunders distribution, which has not been studied in the setting of neural activity. We validate this expansion with original experimental and simulated electrophysiological data. PMID:25998210

  8. Persistent neural activity in head direction cells

    NASA Technical Reports Server (NTRS)

    Taube, Jeffrey S.; Bassett, Joshua P.; Oman, C. M. (Principal Investigator)

    2003-01-01

    Many neurons throughout the rat limbic system discharge in relation to the animal's directional heading with respect to its environment. These so-called head direction (HD) cells exhibit characteristics of persistent neural activity. This article summarizes where HD cells are found, their major properties, and some of the important experiments that have been conducted to elucidate how this signal is generated. The number of HD and angular head velocity cells was estimated for several brain areas involved in the generation of the HD signal, including the postsubiculum, anterior dorsal thalamus, lateral mammillary nuclei and dorsal tegmental nucleus. The HD cell signal has many features in common with what is known about how neural integration is accomplished in the oculomotor system. The nature of the HD cell signal makes it an attractive candidate for using neural network models to elucidate the signal's underlying mechanisms. The conditions that any network model must satisfy in order to accurately represent how the nervous system generates this signal are highlighted and areas where key information is missing are discussed.

  9. Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance

    PubMed Central

    Palle, Komaraiah; Mani, Chinnadurai; Tripathi, Kaushlendra; Athar, Mohammad

    2015-01-01

    The canonical hedgehog (HH) pathway is a multicomponent signaling cascade (HH, protein patched homolog 1 (PTCH1), smoothened (SMO)) that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (GLI1), GLI2 and GLI3. Activation of GLIs must be tightly regulated as they modulate target genes which control tissue patterning, stem cell maintenance, and differentiation during development. However, dysregulation or mutations in HH signaling leads to genomic instability (GI) and various cancers, for example, germline mutation in PTCH1 lead to Gorlin syndrome, a condition where patients develop numerous basal cell carcinomas and rarely rhabdomyosarcoma (RMS). Activating mutations in SMO have also been recognized in sporadic cases of medulloblastoma and SMO is overexpressed in many other cancers. Recently, studies in several human cancers have shown that GLI1 expression is independent from HH ligand and canonical intracellular signaling through PTCH and SMO. In fact, this aberrantly regulated GLI1 has been linked to several non-canonical oncogenic growth signals such as Kirsten rat sarcoma viral oncogene homolog (KRAS), avian myelocytomatosis virus oncogene cellular homolog (C-MYC), transforming growth factor β (TGFβ), wingless-type MMTV integration site family (WNT) and β-catenin. Recent studies from our lab and other independent studies demonstrate that aberrantly expressed GLI1 influences the integrity of several DNA damage response and repair signals, and if altered, these networks can contribute to GI and impact tumor response to chemo- and radiation therapies. Furthermore, the ineffectiveness of SMO inhibitors in clinical studies argues for the development of GLI1-specific inhibitors in order to develop effective therapeutic modalities to treat these tumors. In this review, we focus on summarizing current understanding of the molecular, biochemical and cellular basis for

  10. Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance.

    PubMed

    Palle, Komaraiah; Mani, Chinnadurai; Tripathi, Kaushlendra; Athar, Mohammad

    2015-01-01

    The canonical hedgehog (HH) pathway is a multicomponent signaling cascade (HH, protein patched homolog 1 (PTCH1), smoothened (SMO)) that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (GLI1), GLI2 and GLI3. Activation of GLIs must be tightly regulated as they modulate target genes which control tissue patterning, stem cell maintenance, and differentiation during development. However, dysregulation or mutations in HH signaling leads to genomic instability (GI) and various cancers, for example, germline mutation in PTCH1 lead to Gorlin syndrome, a condition where patients develop numerous basal cell carcinomas and rarely rhabdomyosarcoma (RMS). Activating mutations in SMO have also been recognized in sporadic cases of medulloblastoma and SMO is overexpressed in many other cancers. Recently, studies in several human cancers have shown that GLI1 expression is independent from HH ligand and canonical intracellular signaling through PTCH and SMO. In fact, this aberrantly regulated GLI1 has been linked to several non-canonical oncogenic growth signals such as Kirsten rat sarcoma viral oncogene homolog (KRAS), avian myelocytomatosis virus oncogene cellular homolog (C-MYC), transforming growth factor β (TGFβ), wingless-type MMTV integration site family (WNT) and β-catenin. Recent studies from our lab and other independent studies demonstrate that aberrantly expressed GLI1 influences the integrity of several DNA damage response and repair signals, and if altered, these networks can contribute to GI and impact tumor response to chemo- and radiation therapies. Furthermore, the ineffectiveness of SMO inhibitors in clinical studies argues for the development of GLI1-specific inhibitors in order to develop effective therapeutic modalities to treat these tumors. In this review, we focus on summarizing current understanding of the molecular, biochemical and cellular basis for

  11. Aberrant neural signatures of decision-making: Pathological gamblers display cortico-striatal hypersensitivity to extreme gambles.

    PubMed

    Gelskov, Sofie V; Madsen, Kristoffer H; Ramsøy, Thomas Z; Siebner, Hartwig R

    2016-03-01

    Pathological gambling is an addictive disorder characterized by an irresistible urge to gamble despite severe consequences. One of the hallmarks of pathological gambling is maladaptive and highly risky decision-making, which has been linked to dysregulation of reward-related brain regions such as the ventral striatum. However, previous studies have produced contradictory results regarding the implication of this network, revealing either hypo- or hypersensitivity to monetary gains and losses. One possible explanation is that the gambling brain might be misrepresenting the benefits and costs when weighting the potential outcomes, and not the gains and losses per se. To address this issue, we investigated whether pathological gambling is associated with abnormal brain activity during decisions that weight the utility of possible gains against possible losses. Pathological gamblers and healthy human subjects underwent functional magnetic resonance imaging while they accepted or rejected mixed gain/loss gambles with fifty-fifty chances of winning or losing. Contrary to healthy individuals, gamblers showed a U-shaped response profile reflecting hypersensitivity to the most appetitive and most aversive bets in an executive cortico-striatal network including the dorsolateral prefrontal cortex and caudate nucleus. This network is concerned with the evaluation of action-outcome contingencies, monitoring recent actions and anticipating their consequences. The dysregulation of this specific network, especially for extreme bets with large potentials consequences, offers a novel understanding of the neural basis of pathological gambling in terms of deficient associations between gambling actions and their financial impact. PMID:26780575

  12. Aberrant Lipid Metabolism in the Forebrain Niche Suppresses Adult Neural Stem Cell Proliferation in an Animal Model of Alzheimer's Disease.

    PubMed

    Hamilton, Laura K; Dufresne, Martin; Joppé, Sandra E; Petryszyn, Sarah; Aumont, Anne; Calon, Frédéric; Barnabé-Heider, Fanie; Furtos, Alexandra; Parent, Martin; Chaurand, Pierre; Fernandes, Karl J L

    2015-10-01

    Lipid metabolism is fundamental for brain development and function, but its roles in normal and pathological neural stem cell (NSC) regulation remain largely unexplored. Here, we uncover a fatty acid-mediated mechanism suppressing endogenous NSC activity in Alzheimer's disease (AD). We found that postmortem AD brains and triple-transgenic Alzheimer's disease (3xTg-AD) mice accumulate neutral lipids within ependymal cells, the main support cell of the forebrain NSC niche. Mass spectrometry and microarray analyses identified these lipids as oleic acid-enriched triglycerides that originate from niche-derived rather than peripheral lipid metabolism defects. In wild-type mice, locally increasing oleic acid was sufficient to recapitulate the AD-associated ependymal triglyceride phenotype and inhibit NSC proliferation. Moreover, inhibiting the rate-limiting enzyme of oleic acid synthesis rescued proliferative defects in both adult neurogenic niches of 3xTg-AD mice. These studies support a pathogenic mechanism whereby AD-induced perturbation of niche fatty acid metabolism suppresses the homeostatic and regenerative functions of NSCs. PMID:26321199

  13. Altered Theta Oscillations and Aberrant Cortical Excitatory Activity in the 5XFAD Model of Alzheimer's Disease

    PubMed Central

    Siwek, Magdalena Elisabeth; Müller, Ralf; Henseler, Christina; Trog, Astrid; Lundt, Andreas; Wormuth, Carola; Broich, Karl; Weiergräber, Marco; Papazoglou, Anna

    2015-01-01

    Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by impairment of memory function. The 5XFAD mouse model was analyzed and compared with wild-type (WT) controls for aberrant cortical excitability and hippocampal theta oscillations by using simultaneous video-electroencephalogram (EEG) monitoring. Seizure staging revealed that 5XFAD mice exhibited cortical hyperexcitability whereas controls did not. In addition, 5XFAD mice displayed a significant increase in hippocampal theta activity from the light to dark phase during nonmotor activity. We also observed a reduction in mean theta frequency in 5XFAD mice compared to controls that was again most prominent during nonmotor activity. Transcriptome analysis of hippocampal probes and subsequent qPCR validation revealed an upregulation of Plcd4 that might be indicative of enhanced muscarinic signalling. Our results suggest that 5XFAD mice exhibit altered cortical excitability, hippocampal dysrhythmicity, and potential changes in muscarinic signaling. PMID:25922768

  14. Deep Neural Networks with Multistate Activation Functions

    PubMed Central

    Cai, Chenghao; Xu, Yanyan; Ke, Dengfeng; Su, Kaile

    2015-01-01

    We propose multistate activation functions (MSAFs) for deep neural networks (DNNs). These MSAFs are new kinds of activation functions which are capable of representing more than two states, including the N-order MSAFs and the symmetrical MSAF. DNNs with these MSAFs can be trained via conventional Stochastic Gradient Descent (SGD) as well as mean-normalised SGD. We also discuss how these MSAFs perform when used to resolve classification problems. Experimental results on the TIMIT corpus reveal that, on speech recognition tasks, DNNs with MSAFs perform better than the conventional DNNs, getting a relative improvement of 5.60% on phoneme error rates. Further experiments also reveal that mean-normalised SGD facilitates the training processes of DNNs with MSAFs, especially when being with large training sets. The models can also be directly trained without pretraining when the training set is sufficiently large, which results in a considerable relative improvement of 5.82% on word error rates. PMID:26448739

  15. Active voltammetric microsensors with neural signal processing.

    SciTech Connect

    Vogt, M. C.

    1998-12-11

    Many industrial and environmental processes, including bioremediation, would benefit from the feedback and control information provided by a local multi-analyte chemical sensor. For most processes, such a sensor would need to be rugged enough to be placed in situ for long-term remote monitoring, and inexpensive enough to be fielded in useful numbers. The multi-analyte capability is difficult to obtain from common passive sensors, but can be provided by an active device that produces a spectrum-type response. Such new active gas microsensor technology has been developed at Argonne National Laboratory. The technology couples an electrocatalytic ceramic-metallic (cermet) microsensor with a voltammetric measurement technique and advanced neural signal processing. It has been demonstrated to be flexible, rugged, and very economical to produce and deploy. Both narrow interest detectors and wide spectrum instruments have been developed around this technology. Much of this technology's strength lies in the active measurement technique employed. The technique involves applying voltammetry to a miniature electrocatalytic cell to produce unique chemical ''signatures'' from the analytes. These signatures are processed with neural pattern recognition algorithms to identify and quantify the components in the analyte. The neural signal processing allows for innovative sampling and analysis strategies to be employed with the microsensor. In most situations, the whole response signature from the voltammogram can be used to identify, classify, and quantify an analyte, without dissecting it into component parts. This allows an instrument to be calibrated once for a specific gas or mixture of gases by simple exposure to a multi-component standard rather than by a series of individual gases. The sampled unknown analytes can vary in composition or in concentration, the calibration, sensing, and processing methods of these active voltammetric microsensors can detect, recognize, and

  16. Inhibition of aberrant complement activation by a dimer of acetylsalicylic acid.

    PubMed

    Lee, Moonhee; Wathier, Matthew; Love, Jennifer A; McGeer, Edith; McGeer, Patrick L

    2015-10-01

    We here report synthesis for the first time of the acetyl salicylic acid dimer 5,5'-methylenebis(2-acetoxybenzoic acid) (DAS). DAS inhibits aberrant complement activation by selectively blocking factor D of the alternative complement pathway and C9 of the membrane attack complex. We have previously identified aurin tricarboxylic and its oligomers as promising agents in this regard. DAS is much more potent, inhibiting erythrocyte hemolysis by complement-activated serum with an IC50 in the 100-170 nanomolar range. There are numerous conditions where self-damage from the complement system has been implicated in the pathology, including such chronic degenerative diseases of aging as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and age-related macular degeneration. Consequently, there is a high priority for the discovery and development of agents that can successfully treat such conditions. DAS holds considerable promise for being such an agent. PMID:26248865

  17. Understanding the brain by controlling neural activity

    PubMed Central

    Krug, Kristine; Salzman, C. Daniel; Waddell, Scott

    2015-01-01

    Causal methods to interrogate brain function have been employed since the advent of modern neuroscience in the nineteenth century. Initially, randomly placed electrodes and stimulation of parts of the living brain were used to localize specific functions to these areas. Recent technical developments have rejuvenated this approach by providing more precise tools to dissect the neural circuits underlying behaviour, perception and cognition. Carefully controlled behavioural experiments have been combined with electrical devices, targeted genetically encoded tools and neurochemical approaches to manipulate information processing in the brain. The ability to control brain activity in these ways not only deepens our understanding of brain function but also provides new avenues for clinical intervention, particularly in conditions where brain processing has gone awry. PMID:26240417

  18. An Activity for Demonstrating the Concept of a Neural Circuit

    ERIC Educational Resources Information Center

    Kreiner, David S.

    2012-01-01

    College students in two sections of a general psychology course participated in a demonstration of a simple neural circuit. The activity was based on a neural circuit that Jeffress proposed for localizing sounds. Students in one section responded to a questionnaire prior to participating in the activity, while students in the other section…

  19. Identifying Emotions on the Basis of Neural Activation.

    PubMed

    Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

    2013-01-01

    We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing. PMID:23840392

  20. Differentiated Effects of Sensory Activities as Abolishing Operations via Non-Contingent Reinforcement on Academic and Aberrant Behavior

    ERIC Educational Resources Information Center

    Mancil, G. Richmond; Haydon, Todd; Boman, Marty

    2016-01-01

    The purpose of the study was to evaluate the effectiveness of sensory activities used as antecedent interventions on the percentage correct on academic tasks and rate of aberrant behavior in three elementary aged children with Autism Spectrum Disorders (ASD). Study activities were conducted in an after school program for children with ASD where…

  1. Quantitative modeling of multiscale neural activity

    NASA Astrophysics Data System (ADS)

    Robinson, Peter A.; Rennie, Christopher J.

    2007-01-01

    The electrical activity of the brain has been observed for over a century and is widely used to probe brain function and disorders, chiefly through the electroencephalogram (EEG) recorded by electrodes on the scalp. However, the connections between physiology and EEGs have been chiefly qualitative until recently, and most uses of the EEG have been based on phenomenological correlations. A quantitative mean-field model of brain electrical activity is described that spans the range of physiological and anatomical scales from microscopic synapses to the whole brain. Its parameters measure quantities such as synaptic strengths, signal delays, cellular time constants, and neural ranges, and are all constrained by independent physiological measurements. Application of standard techniques from wave physics allows successful predictions to be made of a wide range of EEG phenomena, including time series and spectra, evoked responses to stimuli, dependence on arousal state, seizure dynamics, and relationships to functional magnetic resonance imaging (fMRI). Fitting to experimental data also enables physiological parameters to be infered, giving a new noninvasive window into brain function, especially when referenced to a standardized database of subjects. Modifications of the core model to treat mm-scale patchy interconnections in the visual cortex are also described, and it is shown that resulting waves obey the Schroedinger equation. This opens the possibility of classical cortical analogs of quantum phenomena.

  2. Epithelial Mesenchymal Transition Induces Aberrant Glycosylation through Hexosamine Biosynthetic Pathway Activation.

    PubMed

    Lucena, Miguel C; Carvalho-Cruz, Patricia; Donadio, Joana L; Oliveira, Isadora A; de Queiroz, Rafaela M; Marinho-Carvalho, Monica M; Sola-Penna, Mauro; de Paula, Iron F; Gondim, Katia C; McComb, Mark E; Costello, Catherine E; Whelan, Stephen A; Todeschini, Adriane R; Dias, Wagner B

    2016-06-17

    Deregulated cellular metabolism is a hallmark of tumors. Cancer cells increase glucose and glutamine flux to provide energy needs and macromolecular synthesis demands. Several studies have been focused on the importance of glycolysis and pentose phosphate pathway. However, a neglected but very important branch of glucose metabolism is the hexosamine biosynthesis pathway (HBP). The HBP is a branch of the glucose metabolic pathway that consumes ∼2-5% of the total glucose, generating UDP-GlcNAc as the end product. UDP-GlcNAc is the donor substrate used in multiple glycosylation reactions. Thus, HBP links the altered metabolism with aberrant glycosylation providing a mechanism for cancer cells to sense and respond to microenvironment changes. Here, we investigate the changes of glucose metabolism during epithelial mesenchymal transition (EMT) and the role of O-GlcNAcylation in this process. We show that A549 cells increase glucose uptake during EMT, but instead of increasing the glycolysis and pentose phosphate pathway, the glucose is shunted through the HBP. The activation of HBP induces an aberrant cell surface glycosylation and O-GlcNAcylation. The cell surface glycans display an increase of sialylation α2-6, poly-LacNAc, and fucosylation, all known epitopes found in different tumor models. In addition, modulation of O-GlcNAc levels was demonstrated to be important during the EMT process. Taken together, our results indicate that EMT is an applicable model to study metabolic and glycophenotype changes during carcinogenesis, suggesting that cell glycosylation senses metabolic changes and modulates cell plasticity. PMID:27129262

  3. Neural network with formed dynamics of activity

    SciTech Connect

    Dunin-Barkovskii, V.L.; Osovets, N.B.

    1995-03-01

    The problem of developing a neural network with a given pattern of the state sequence is considered. A neural network structure and an algorithm, of forming its bond matrix which lead to an approximate but robust solution of the problem are proposed and discussed. Limiting characteristics of the serviceability of the proposed structure are studied. Various methods of visualizing dynamic processes in a neural network are compared. Possible applications of the results obtained for interpretation of neurophysiological data and in neuroinformatics systems are discussed.

  4. Graphene microelectrode arrays for neural activity detection.

    PubMed

    Du, Xiaowei; Wu, Lei; Cheng, Ji; Huang, Shanluo; Cai, Qi; Jin, Qinghui; Zhao, Jianlong

    2015-09-01

    We demonstrate a method to fabricate graphene microelectrode arrays (MEAs) using a simple and inexpensive method to solve the problem of opaque electrode positions in traditional MEAs, while keeping good biocompatibility. To study the interface differences between graphene-electrolyte and gold-electrolyte, graphene and gold electrodes with a large area were fabricated. According to the simulation results of electrochemical impedances, the gold-electrolyte interface can be described as a classical double-layer structure, while the graphene-electrolyte interface can be explained by a modified double-layer theory. Furthermore, using graphene MEAs, we detected the neural activities of neurons dissociated from Wistar rats (embryonic day 18). The signal-to-noise ratio of the detected signal was 10.31 ± 1.2, which is comparable to those of MEAs made with other materials. The long-term stability of the MEAs is demonstrated by comparing differences in Bode diagrams taken before and after cell culturing. PMID:25712492

  5. Activity-dependent neural plasticity from bench to bedside.

    PubMed

    Ganguly, Karunesh; Poo, Mu-Ming

    2013-10-30

    Much progress has been made in understanding how behavioral experience and neural activity can modify the structure and function of neural circuits during development and in the adult brain. Studies of physiological and molecular mechanisms underlying activity-dependent plasticity in animal models have suggested potential therapeutic approaches for a wide range of brain disorders in humans. Physiological and electrical stimulations as well as plasticity-modifying molecular agents may facilitate functional recovery by selectively enhancing existing neural circuits or promoting the formation of new functional circuits. Here, we review the advances in basic studies of neural plasticity mechanisms in developing and adult nervous systems and current clinical treatments that harness neural plasticity, and we offer perspectives on future development of plasticity-based therapy. PMID:24183023

  6. Identifying the structural requirements for chromosomal aberration by incorporating molecular flexibility and metabolic activation of chemicals.

    PubMed

    Mekenyan, Ovanes; Todorov, Milen; Serafimova, Rossitsa; Stoeva, Stoyanka; Aptula, Aynur; Finking, Robert; Jacob, Elard

    2007-12-01

    Modeling the potential of chemicals to induce chromosomal damage has been hampered by the diversity of mechanisms which condition this biological effect. The direct binding of a chemical to DNA is one of the underlying mechanisms that is also responsible for bacterial mutagenicity. Disturbance of DNA synthesis due to inhibition of topoisomerases and interaction of chemicals with nuclear proteins associated with DNA (e.g., histone proteins) were identified as additional mechanisms leading to chromosomal aberrations (CA). A comparative analysis of in vitro genotoxic data for a large number of chemicals revealed that more than 80% of chemicals that elicit bacterial mutagenicity (as indicated by the Ames test) also induce CA; alternatively, only 60% of chemicals that induce CA have been found to be active in the Ames test. In agreement with this relationship, a battery of models is developed for modeling CA. It combines the Ames model for bacterial mutagenicity, which has already been derived and integrated into the Optimized Approach Based on Structural Indices Set (OASIS) tissue metabolic simulator (TIMES) platform, and a newly derived model accounting for additional mechanisms leading to CA. Both models are based on the classical concept of reactive alerts. Some of the specified alerts interact directly with DNA or nuclear proteins, whereas others are applied in a combination of two- or three-dimensional quantitative structure-activity relationship models assessing the degree of activation of the alerts from the rest of the molecules. The use of each of the alerts has been justified by a mechanistic interpretation of the interaction. In combination with a rat liver S9 metabolism simulator, the model explained the CA induced by metabolically activated chemicals that do not elicit activity in the parent form. The model can be applied in two ways: with and without metabolic activation of chemicals. PMID:18052113

  7. Mesoscopic Patterns of Neural Activity Support Songbird Cortical Sequences

    PubMed Central

    Guitchounts, Grigori; Velho, Tarciso; Lois, Carlos; Gardner, Timothy J.

    2015-01-01

    Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From “time cells” in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia–projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song. PMID:26039895

  8. Mesoscopic patterns of neural activity support songbird cortical sequences.

    PubMed

    Markowitz, Jeffrey E; Liberti, William A; Guitchounts, Grigori; Velho, Tarciso; Lois, Carlos; Gardner, Timothy J

    2015-06-01

    Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From "time cells" in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia-projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song. PMID:26039895

  9. Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors

    PubMed Central

    Edri, Reuven; Yaffe, Yakey; Ziller, Michael J.; Mutukula, Naresh; Volkman, Rotem; David, Eyal; Jacob-Hirsch, Jasmine; Malcov, Hagar; Levy, Carmit; Rechavi, Gideon; Gat-Viks, Irit; Meissner, Alexander; Elkabetz, Yechiel

    2015-01-01

    Decoding heterogeneity of pluripotent stem cell (PSC)-derived neural progeny is fundamental for revealing the origin of diverse progenitors, for defining their lineages, and for identifying fate determinants driving transition through distinct potencies. Here we have prospectively isolated consecutively appearing PSC-derived primary progenitors based on their Notch activation state. We first isolate early neuroepithelial cells and show their broad Notch-dependent developmental and proliferative potential. Neuroepithelial cells further yield successive Notch-dependent functional primary progenitors, from early and midneurogenic radial glia and their derived basal progenitors, to gliogenic radial glia and adult-like neural progenitors, together recapitulating hallmarks of neural stem cell (NSC) ontogeny. Gene expression profiling reveals dynamic stage-specific transcriptional patterns that may link development of distinct progenitor identities through Notch activation. Our observations provide a platform for characterization and manipulation of distinct progenitor cell types amenable for developing streamlined neural lineage specification paradigms for modelling development in health and disease. PMID:25799239

  10. Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000.

    PubMed

    Stoupel, Eliahu G; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

    2005-09-01

    The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth--138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices--sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999--were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected--r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS. PMID:15988607

  11. Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990-2000

    NASA Astrophysics Data System (ADS)

    Stoupel, Eliahu G.; Frimer, Helena; Appelman, Zvi; Ben-Neriah, Ziva; Dar, Hanna; Fejgin, Moshe D.; Gershoni-Baruch, Ruth; Manor, Esther; Barkai, Gad; Shalev, Stavit; Gelman-Kohan, Zully; Reish, Orit; Lev, Dorit; Davidov, Bella; Goldman, Boleslaw; Shohat, Mordechai

    2005-09-01

    The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990-2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth—138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices—sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989-1999—were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected—r=-0.78, P=0.008 for sunspot number and r=-0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.

  12. Social stress, autonomic neural activation, and cardiac activity in rats.

    PubMed

    Sgoifo, A; Koolhaas, J; De Boer, S; Musso, E; Stilli, D; Buwalda, B; Meerlo, P

    1999-11-01

    Animal models of social stress represent a useful experimental tool to investigate the relationship between psychological stress, autonomic neural activity and cardiovascular disease. This paper summarizes the results obtained in a series of experiments performed on rats and aimed at verifying whether social challenges produce specific modifications in the autonomic neural control of heart rate and whether these changes can be detrimental for cardiac electrical stability. Short-term electrocardiographic recordings were performed via radiotelemetry and the autonomic input to the heart evaluated by means of time-domain heart rate variability measures. Compared to other stress contexts, a social defeat experience produces a strong shift of autonomic balance toward sympathetic dominance, poorly antagonized by vagal rebound, and associated with the occurrence of cardiac tachyarrhythmias. These effects were particularly severe when a wild-type strain of rats was studied. The data also suggest that the cardiac autonomic responses produced by different types of social contexts (dominant-subordinate interaction, dominant-dominant confrontation, social defeat) are related to different degrees of emotional activation, which in turn are likely modulated by the social rank of the experimental animal and the opponent, the prior experience with the stressor, and the level of controllability over the stimulus. PMID:10580306

  13. Aberrant Activation of TGF-β in Subchondral Bone at the Onset of Rheumatoid Arthritis Joint Destruction

    PubMed Central

    Xu, Xin; Zheng, Liwei; Bian, Qin; Xie, Liang; Liu, Wenlong; Zhen, Gehua; Crane, Janet L; Zhou, Xuedong; Cao, Xu

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease that often leads to joint destruction. A myriad of drugs targeting the immune abnormalities and downstream inflammatory cascades have been developed, but the joint destruction is not effectively halted. Here we report that aberrant activation of TGF-β in the subchondral bone marrow by immune response increases osteoprogenitors and uncoupled bone resorption and formation in RA mouse/rat models. Importantly, either systemic or local blockade of TGF-β activity in the subchondral bone attenuated articular cartilage degeneration in RA. Moreover, conditional deletion of TGF-β receptor II (Tgfbr2) in nestin-positive cells also effectively halted progression of RA joint destruction. Our data demonstrate that aberrant activation of TGF-β in the subchondral bone is involved at the onset of RA joint cartilage degeneration. Thus, modulation of subchondral bone TGF-β activity could be a potential therapy for RA joint destruction. PMID:25967237

  14. In-flight aberrations corrections for large space telescopes using active optics

    NASA Astrophysics Data System (ADS)

    Laslandes, M.; Ferrari, M.; Hugot, E.; Lemaitre, G.

    2010-07-01

    The need for both high quality images and light structures is a constant concern in the conception of space telescopes. The goal here is to determine how an active optics system could be embarked on a satellite in order to correct the wave front deformations of the optical train. The optical aberrations appearing in a space environment are due to mirrors' deformations, with three main origins: the thermal variations, the weightlessness in space with respect to the Assemblage, Integration and Testing (AIT) conditions on ground and the use of large weightlighted primary mirrors. We are developing a model of deformable mirror as minimalist as possible, especially in term of number of actuators, which is able to correct the first Zernike polynomials in the specified range of amplitude and precision. Flight constraints as weight, volume and power consumption have to be considered. Firstly, such a system is designed according to the equations from the elasticity theory: we determine the geometrical and mechanical characteristics of the mirror, the location of the forces to be applied and the way to apply them. The concept is validated with a Finite Element Analysis (FEA), allowing optimizing the system by taking into account parameters absent from the theory. At the end of the program the mirror will be realized and characterized in a representative optical configuration.

  15. Neural Activity Reveals Preferences Without Choices

    PubMed Central

    Smith, Alec; Bernheim, B. Douglas; Camerer, Colin

    2014-01-01

    We investigate the feasibility of inferring the choices people would make (if given the opportunity) based on their neural responses to the pertinent prospects when they are not engaged in actual decision making. The ability to make such inferences is of potential value when choice data are unavailable, or limited in ways that render standard methods of estimating choice mappings problematic. We formulate prediction models relating choices to “non-choice” neural responses and use them to predict out-of-sample choices for new items and for new groups of individuals. The predictions are sufficiently accurate to establish the feasibility of our approach. PMID:25729468

  16. OCT detection of neural activity in American cockroach nervous system

    NASA Astrophysics Data System (ADS)

    Gorczyńska, Iwona; Wyszkowska, Joanna; Bukowska, Danuta; Ruminski, Daniel; Karnowski, Karol; Stankiewicz, Maria; Wojtkowski, Maciej

    2013-03-01

    We show results of a project which focuses on detection of activity in neural tissue with Optical Coherence Tomography (OCT) methods. Experiments were performed in neural cords dissected from the American cockroach (Periplaneta americana L.). Functional OCT imaging was performed with ultrahigh resolution spectral / Fourier domain OCT system (axial resolution 2.5 μm). Electrical stimulation (voltage pulses) was applied to the sensory cercal nerve of the neural cord. Optical detection of functional activation of the sample was performed in the connective between the terminal abdominal ganglion and the fifth abdominal ganglion. Functional OCT data were collected over time with the OCT beam illuminating selected single point in the connectives (i.e. OCT M-scans were acquired). Phase changes of the OCT signal were analyzed to visualize occurrence of activation in the neural cord. Electrophysiology recordings (microelectrode method) were also performed as a reference method to demonstrate electrical response of the sample to stimulation.

  17. Active Sampling in Evolving Neural Networks.

    ERIC Educational Resources Information Center

    Parisi, Domenico

    1997-01-01

    Comments on Raftopoulos article (PS 528 649) on facilitative effect of cognitive limitation in development and connectionist models. Argues that the use of neural networks within an "Artificial Life" perspective can more effectively contribute to the study of the role of cognitive limitations in development and their genetic basis than can using…

  18. Monitoring Neural Activity with Bioluminescence during Natural Behavior

    PubMed Central

    Naumann, Eva A.; Kampff, Adam R.; Prober, David A.; Schier, Alexander F.; Engert, Florian

    2010-01-01

    Existing techniques for monitoring neural activity in awake, freely behaving vertebrates are invasive and difficult to target to genetically identified neurons. Here we describe the use of bioluminescence to non-invasively monitor the activity of genetically specified neurons in freely behaving zebrafish. Transgenic fish expressing the Ca2+-sensitive photoprotein GFP-apoAequorin (GA) in most neurons generated large and fast bioluminescent signals related to neural activity, neuroluminescence, that could be recorded continuously for many days. To test the limits of this technique, GA was specifically targeted to the hypocretin-positive neurons of the hypothalamus. We found that neuroluminescence generated by this group of ~20 neurons was associated with periods of increased locomotor activity and identified two classes of neural activity corresponding to distinct swim latencies. Thus, our neuroluminescence assay can report, with high temporal resolution and sensitivity, the activity of small subsets of neurons during unrestrained behavior. PMID:20305645

  19. Lag Synchronization of Switched Neural Networks via Neural Activation Function and Applications in Image Encryption.

    PubMed

    Wen, Shiping; Zeng, Zhigang; Huang, Tingwen; Meng, Qinggang; Yao, Wei

    2015-07-01

    This paper investigates the problem of global exponential lag synchronization of a class of switched neural networks with time-varying delays via neural activation function and applications in image encryption. The controller is dependent on the output of the system in the case of packed circuits, since it is hard to measure the inner state of the circuits. Thus, it is critical to design the controller based on the neuron activation function. Comparing the results, in this paper, with the existing ones shows that we improve and generalize the results derived in the previous literature. Several examples are also given to illustrate the effectiveness and potential applications in image encryption. PMID:25594985

  20. Neural net forecasting for geomagnetic activity

    NASA Technical Reports Server (NTRS)

    Hernandez, J. V.; Tajima, T.; Horton, W.

    1993-01-01

    We use neural nets to construct nonlinear models to forecast the AL index given solar wind and interplanetary magnetic field (IMF) data. We follow two approaches: (1) the state space reconstruction approach, which is a nonlinear generalization of autoregressive-moving average models (ARMA) and (2) the nonlinear filter approach, which reduces to a moving average model (MA) in the linear limit. The database used here is that of Bargatze et al. (1985).

  1. Reduced respiratory neural activity elicits phrenic motor facilitation.

    PubMed

    Mahamed, Safraaz; Strey, Kristi A; Mitchell, Gordon S; Baker-Herman, Tracy L

    2011-03-15

    We hypothesized that reduced respiratory neural activity elicits compensatory mechanisms of plasticity that enhance respiratory motor output. In urethane-anesthetized and ventilated rats, we reversibly reduced respiratory neural activity for 25-30 min using: hypocapnia (end tidal CO(2)=30 mmHg), isoflurane (~1%) or high frequency ventilation (HFV; ~100 breaths/min). In all cases, increased phrenic burst amplitude was observed following restoration of respiratory neural activity (hypocapnia: 92±22%; isoflurane: 65±22%; HFV: 54±13% baseline), which was significantly greater than time controls receiving the same surgery, but no interruptions in respiratory neural activity (3±5% baseline, p<0.05). Hypocapnia also elicited transient increases in respiratory burst frequency (9±2 versus 1±1bursts/min, p<0.05). Our results suggest that reduced respiratory neural activity elicits a unique form of plasticity in respiratory motor control which we refer to as inactivity-induced phrenic motor facilitation (iPMF). iPMF may prevent catastrophic decreases in respiratory motor output during ventilatory control disorders associated with abnormal respiratory activity. PMID:21167322

  2. Reduced respiratory neural activity elicits phrenic motor facilitation

    PubMed Central

    Mahamed, Safraaz; Strey, Kristi A.; Mitchell, Gordon S.; Baker-Herman, Tracy L.

    2011-01-01

    We hypothesized that reduced respiratory neural activity elicits compensatory mechanisms of plasticity that enhance respiratory motor output. In urethane-anesthetized and ventilated rats, we reversibly reduced respiratory neural activity for 25–30 min using: hypocapnia (end tidal CO2 = 30 mmHg), isoflurane (~ 1%) or high frequency ventilation (HFV; ~100 breaths/min). In all cases, increased phrenic burst amplitude was observed following restoration of respiratory neural activity (hypocapnia: 92 ± 22%; isoflurane: 65 ± 22%; HFV: 54 ± 13% baseline), which was significantly greater than time controls receiving the same surgery, but no interruptions in respiratory neural activity (3 ± 5% baseline, p<0.05). Hypocapnia also elicited transient increases in respiratory burst frequency (9 ± 2 versus 1 ± 1 bursts/min, p<0.05). Our results suggest that reduced respiratory neural activity elicits a unique form of plasticity in respiratory motor control which we refer to as inactivity-induced phrenic motor facilitation (iPMF). iPMF may prevent catastrophic decreases in respiratory motor output during ventilatory control disorders associated with abnormal respiratory activity. PMID:21167322

  3. Optical imaging of neural and hemodynamic brain activity

    NASA Astrophysics Data System (ADS)

    Schei, Jennifer Lynn

    Optical imaging technologies can be used to record neural and hemodynamic activity. Neural activity elicits physiological changes that alter the optical tissue properties. Specifically, changes in polarized light are concomitant with neural depolarization. We measured polarization changes from an isolated lobster nerve during action potential propagation using both reflected and transmitted light. In transmission mode, polarization changes were largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. To overcome irregular cell orientation found in the brain, we measured polarization changes from a nerve tied in a knot. Our results show that neural activation produces polarization changes that can be imaged even without regular cell orientations. Neural activation expends energy resources and elicits metabolic delivery through blood vessel dilation, increasing blood flow and volume. We used spectroscopic imaging techniques combined with electrophysiological measurements to record evoked neural and hemodynamic responses from the auditory cortex of the rat. By using implantable optics, we measured responses across natural wake and sleep states, as well as responses following different amounts of sleep deprivation. During quiet sleep, evoked metabolic responses were larger compared to wake, perhaps because blood vessels were more compliant. When animals were sleep deprived, evoked hemodynamic responses were smaller following longer periods of deprivation. These results suggest that prolonged neural activity through sleep deprivation may diminish vascular compliance as indicated by the blunted vascular response. Subsequent sleep may allow vessels to relax, restoring their ability to deliver blood. These results also suggest that severe sleep deprivation or chronic

  4. Social status modulates neural activity in the mentalizing network

    PubMed Central

    Muscatell, Keely A.; Morelli, Sylvia A.; Falk, Emily B.; Way, Baldwin M.; Pfeifer, Jennifer H.; Galinsky, Adam D.; Lieberman, Matthew D.; Dapretto, Mirella; Eisenberger, Naomi I.

    2013-01-01

    The current research explored the neural mechanisms linking social status to perceptions of the social world. Two fMRI studies provide converging evidence that individuals lower in social status are more likely to engage neural circuitry often involved in ‘mentalizing’ or thinking about others' thoughts and feelings. Study 1 found that college students' perception of their social status in the university community was related to neural activity in the mentalizing network (e.g., DMPFC, MPFC, precuneus/PCC) while encoding social information, with lower social status predicting greater neural activity in this network. Study 2 demonstrated that socioeconomic status, an objective indicator of global standing, predicted adolescents' neural activity during the processing of threatening faces, with individuals lower in social status displaying greater activity in the DMPFC, previously associated with mentalizing, and the amygdala, previously associated with emotion/salience processing. These studies demonstrate that social status is fundamentally and neurocognitively linked to how people process and navigate their social worlds. PMID:22289808

  5. A neural networks study of quinone compounds with trypanocidal activity.

    PubMed

    de Molfetta, Fábio Alberto; Angelotti, Wagner Fernando Delfino; Romero, Roseli Aparecida Francelin; Montanari, Carlos Alberto; da Silva, Albérico Borges Ferreira

    2008-10-01

    This work investigates neural network models for predicting the trypanocidal activity of 28 quinone compounds. Artificial neural networks (ANN), such as multilayer perceptrons (MLP) and Kohonen models, were employed with the aim of modeling the nonlinear relationship between quantum and molecular descriptors and trypanocidal activity. The calculated descriptors and the principal components were used as input to train neural network models to verify the behavior of the nets. The best model for both network models (MLP and Kohonen) was obtained with four descriptors as input. The descriptors were T5 (torsion angle), QTS1 (sum of absolute values of the atomic charges), VOLS2 (volume of the substituent at region B) and HOMO-1 (energy of the molecular orbital below HOMO). These descriptors provide information on the kind of interaction that occurs between the compounds and the biological receptor. Both neural network models used here can predict the trypanocidal activity of the quinone compounds with good agreement, with low errors in the testing set and a high correctness rate. Thanks to the nonlinear model obtained from the neural network models, we can conclude that electronic and structural properties are important factors in the interaction between quinone compounds that exhibit trypanocidal activity and their biological receptors. The final ANN models should be useful in the design of novel trypanocidal quinones having improved potency. PMID:18629551

  6. Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer

    PubMed Central

    Meng, Erhong; Menezes, Mitchell E.; Bailey, Sarah K.; Metge, Brandon J.; Buchsbaum, Donald J.; Samant, Rajeev S.; Shevde, Lalita A.

    2016-01-01

    The expression of the tumor suppressor Merlin is compromised in nervous system malignancies due to genomic aberrations. We demonstrated for the first time, that in breast cancer, Merlin protein expression is lost due to proteasome-mediated elimination. Immunohistochemical analysis of tumor tissues from patients with metastatic breast cancer revealed characteristically reduced Merlin expression. Importantly, we identified a functional role for Merlin in impeding breast tumor xenograft growth and reducing invasive characteristics. We sought to determine a possible mechanism by which Merlin accomplishes this reduction in malignant activity. We observed that breast and pancreatic cancer cells with loss of Merlin show an aberrant increase in the activity of β-catenin concomitant with nuclear localization of β-catenin. We discovered that Merlin physically interacts with β-catenin, alters the sub-cellular localization of β-catenin, and significantly reduces the protein levels of β-catenin by targeting it for degradation through the upregulation of Axin1. Consequently, restoration of Merlin inhibited β-catenin-mediated transcriptional activity in breast and pancreatic cancer cells. We also present evidence that loss of Merlin sensitizes tumor cells to inhibition by compounds that target β-catenin-mediated activity. Thus, this study provides compelling evidence that Merlin reduces the malignant activity of pancreatic and breast cancer, in part by suppressing the Wnt/β-catenin pathway. Given the potent role of Wnt/β-catenin signaling in breast and pancreatic cancer and the flurry of activity to test β-catenin inhibitors in the clinic, our findings are opportune and provide evidence for Merlin in restraining aberrant activation of Wnt/β-catenin signaling. PMID:26908451

  7. Encapsulating Elastically Stretchable Neural Interfaces: Yield, Resolution, and Recording/Stimulation of Neural Activity

    PubMed Central

    Morrison, Barclay; Goletiani, Cezar; Yu, Zhe; Wagner, Sigurd

    2013-01-01

    A high resolution elastically stretchable microelectrode array (SMEA) to interface with neural tissue is described. The SMEA consists of an elastomeric substrate, such as poly(dimethylsiloxane) (PDMS), elastically stretchable gold conductors, and an electrically insulating encapsulating layer in which contact holes are opened. We demonstrate the feasibility of producing contact holes with 40 µm × 40 µm openings, show why the adhesion of the encapsulation layer to the underlying silicone substrate is weakened during contact hole fabrication, and provide remedies. These improvements result in greatly increased fabrication yield and reproducibility. An SMEA with 28 microelectrodes was fabricated. The contact holes (100 µm × 100 µm) in the encapsulation layer are only ~10% the size of the previous generation, allowing a larger number of microelectrodes per unit area, thus affording the capability to interface with a smaller neural population per electrode. This new SMEA is used to record spontaneous and evoked activity in organotypic hippocampal tissue slices at 0% strain before stretching, at 5 % and 10 % equibiaxial strain, and again at 0% strain after relaxation. The noise of the recordings increases with increasing strain. The frequency of spontaneous neural activity also increases when the SMEA is stretched. Upon relaxation, the noise returns to pre-stretch levels, while the frequency of neural activity remains elevated. Stimulus-response curves at each strain level are measured. The SMEA shows excellent biocompatibility for at least two weeks. PMID:24093006

  8. Aberrant Activation of Notch Signaling Inhibits PROX1 Activity to Enhance the Malignant Behavior of Thyroid Cancer Cells.

    PubMed

    Choi, Dongwon; Ramu, Swapnika; Park, Eunkyung; Jung, Eunson; Yang, Sara; Jung, Wonhyeuk; Choi, Inho; Lee, Sunju; Kim, Kyu Eui; Seong, Young Jin; Hong, Mingu; Daghlian, George; Kim, Daniel; Shin, Eugene; Seo, Jung In; Khatchadourian, Vicken; Zou, Mengchen; Li, Wei; De Filippo, Roger; Kokorowski, Paul; Chang, Andy; Kim, Steve; Bertoni, Ana; Furlanetto, Tania Weber; Shin, Sung; Li, Meng; Chen, Yibu; Wong, Alex; Koh, Chester; Geliebter, Jan; Hong, Young-Kwon

    2016-02-01

    Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies associated with significant morbidity and mortality. Although multiple studies have contributed to a better understanding of the genetic alterations underlying this frequently arising disease, the downstream molecular effectors that impact PTC pathogenesis remain to be further defined. Here, we report that the regulator of cell fate specification, PROX1, becomes inactivated in PTC through mRNA downregulation and cytoplasmic mislocalization. Expression studies in clinical specimens revealed that aberrantly activated NOTCH signaling promoted PROX1 downregulation and that cytoplasmic mislocalization significantly altered PROX1 protein stability. Importantly, restoration of PROX1 activity in thyroid carcinoma cells revealed that PROX1 not only enhanced Wnt/β-catenin signaling but also regulated several genes known to be associated with PTC, including thyroid cancer protein (TC)-1, SERPINA1, and FABP4. Furthermore, PROX1 reexpression suppressed the malignant phenotypes of thyroid carcinoma cells, such as proliferation, motility, adhesion, invasion, anchorage-independent growth, and polyploidy. Moreover, animal xenograft studies demonstrated that restoration of PROX1 severely impeded tumor formation and suppressed the invasiveness and the nuclear/cytoplasmic ratio of PTC cells. Taken together, our findings demonstrate that NOTCH-induced PROX1 inactivation significantly promotes the malignant behavior of thyroid carcinoma and suggest that PROX1 reactivation may represent a potential therapeutic strategy to attenuate disease progression. PMID:26609053

  9. Polarization Aberrations

    NASA Technical Reports Server (NTRS)

    Mcguire, James P., Jr.; Chipman, Russell A.

    1990-01-01

    The analysis of the polarization characteristics displayed by optical systems can be divided into two categories: geometrical and physical. Geometrical analysis calculates the change in polarization of a wavefront between pupils in an optical instrument. Physical analysis propagates the polarized fields wherever the geometrical analysis is not valid, i.e., near the edges of stops, near images, in anisotropic media, etc. Polarization aberration theory provides a starting point for geometrical design and facilitates subsequent optimization. The polarization aberrations described arise from differences in the transmitted (or reflected) amplitudes and phases at interfaces. The polarization aberration matrix (PAM) is calculated for isotropic rotationally symmetric systems through fourth order and includes the interface phase, amplitude, linear diattenuation, and linear retardance aberrations. The exponential form of Jones matrices used are discussed. The PAM in Jones matrix is introduced. The exact calculation of polarization aberrations through polarization ray tracing is described. The report is divided into three sections: I. Rotationally Symmetric Optical Systems; II. Tilted and Decentered Optical Systems; and Polarization Analysis of LIDARs.

  10. Generating Coherent Patterns of Activity from Chaotic Neural Networks

    PubMed Central

    Sussillo, David; Abbott, L. F.

    2009-01-01

    Neural circuits display complex activity patterns both spontaneously and when responding to a stimulus or generating a motor output. How are these two forms of activity related? We develop a procedure called FORCE learning for modifying synaptic strengths either external to or within a model neural network to change chaotic spontaneous activity into a wide variety of desired activity patterns. FORCE learning works even though the networks we train are spontaneously chaotic and we leave feedback loops intact and unclamped during learning. Using this approach, we construct networks that produce a wide variety of complex output patterns, input-output transformations that require memory, multiple outputs that can be switched by control inputs, and motor patterns matching human motion capture data. Our results reproduce data on pre-movement activity in motor and premotor cortex, and suggest that synaptic plasticity may be a more rapid and powerful modulator of network activity than generally appreciated. PMID:19709635

  11. Topographic organization of Hebbian neural connections by synchronous wave activity

    NASA Astrophysics Data System (ADS)

    Mihaliuk, Eugene; Wackerbauer, Renate; Showalter, Kenneth

    2001-03-01

    Experimental studies have revealed that the refinement of early, imprecise connections in the developing visual system involves activity in the retina before the onset of vision. We study the evolution of initially random unidirectional connections between two excitable layers of FitzHugh-Nagumo neurons with simulated spontaneous activity in the input layer. Lateral coupling within the layers yields synchronous neural wave activity that serves as a template for the Hebbian learning process, which establishes topographically precise interlayer connections.

  12. Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway

    PubMed Central

    Jagani, Zainab; Mora-Blanco, E Lorena; Sansam, Courtney G; McKenna, Elizabeth S; Wilson, Boris; Chen, Dongshu; Klekota, Justin; Tamayo, Pablo; Nguyen, Phuong T L; Tolstorukov, Michael; Park, Peter J; Cho, Yoon-Jae; Hsiao, Kathy; Buonamici, Silvia; Pomeroy, Scott L; Mesirov, Jill P; Ruffner, Heinz; Bouwmeester, Tewis; Luchansky, Sarah J; Murtie, Joshua; Kelleher, Joseph F; Warmuth, Markus; Sellers, William R; Roberts, Charles W M; Dorsch, Marion

    2013-01-01

    Aberrant activation of the Hedgehog (Hh) pathway can drive tumorigenesis1. To investigate the mechanism by which glioma-associated oncogene family zinc finger-1 (GLI1), a crucial effector of Hh signaling2, regulates Hh pathway activation, we searched for GLI1-interacting proteins. We report that the chromatin remodeling protein SNF5 (encoded by SMARCB1, hereafter called SNF5), which is inactivated in human malignant rhabdoid tumors (MRTs), interacts with GLI1. We show that Snf5 localizes to Gli1-regulated promoters and that loss of Snf5 leads to activation of the Hh-Gli pathway. Conversely, re-expression of SNF5 in MRT cells represses GLI1. Consistent with this, we show the presence of a Hh-Gli–activated gene expression profile in primary MRTs and show that GLI1 drives the growth of SNF5-deficient MRT cells in vitro and in vivo. Therefore, our studies reveal that SNF5 is a key mediator of Hh signaling and that aberrant activation of GLI1 is a previously undescribed targetable mechanism contributing to the growth of MRT cells. PMID:21076395

  13. Increasing Endocannabinoid Levels in the Ventral Pallidum Restore Aberrant Dopamine Neuron Activity in the Subchronic PCP Rodent Model of Schizophrenia

    PubMed Central

    Chen, Li; Lodge, Daniel J

    2015-01-01

    Background: Schizophrenia is a debilitating disorder that affects 1% of the US population. While the exogenous administration of cannabinoids such as tetrahydrocannabinol is reported to exacerbate psychosis in schizophrenia patients, augmenting the levels of endogenous cannabinoids has gained attention as a possible alternative therapy to schizophrenia due to clinical and preclinical observations. Thus, patients with schizophrenia demonstrate an inverse relationship between psychotic symptoms and levels of the endocannabinoid anandamide. In addition, increasing endocannabinoid levels (by blockade of enzymatic degradation) has been reported to attenuate social withdrawal in a preclinical model of schizophrenia. Here we examine the effects of increasing endogenous cannabinoids on dopamine neuron activity in the sub-chronic phencyclidine (PCP) model. Aberrant dopamine system function is thought to underlie the positive symptoms of schizophrenia. Methods: Using in vivo extracellular recordings in chloral hydrate–anesthetized rats, we now demonstrate an increase in dopamine neuron population activity in PCP-treated rats. Results: Interestingly, endocannabinoid upregulation, induced by URB-597, was able to normalize this aberrant dopamine neuron activity. Furthermore, we provide evidence that the ventral pallidum is the site where URB-597 acts to restore ventral tegmental area activity. Conclusions: Taken together, we provide preclinical evidence that augmenting endogenous cannabinoids may be an effective therapy for schizophrenia, acting in part to restore ventral pallidal activity. PMID:25539511

  14. Controlling neural activity in Caenorhabditis elegans to evoke chemotactic behavior

    NASA Astrophysics Data System (ADS)

    Kocabas, Askin; Shen, Ching-Han; Guo, Zengcai V.; Ramanathan, Sharad

    2013-03-01

    Animals locate and track chemoattractive gradients in the environment to find food. With its simple nervous system, Caenorhabditis elegans is a good model system in which to understand how the dynamics of neural activity control this search behavior. To understand how the activity in its interneurons coordinate different motor programs to lead the animal to food, here we used optogenetics and new optical tools to manipulate neural activity directly in freely moving animals to evoke chemotactic behavior. By deducing the classes of activity patterns triggered during chemotaxis and exciting individual neurons with these patterns, we identified interneurons that control the essential locomotory programs for this behavior. Notably, we discovered that controlling the dynamics of activity in just one interneuron pair was sufficient to force the animal to locate, turn towards and track virtual light gradients.

  15. Neural Activity When People Solve Verbal Problems with Insight

    PubMed Central

    2004-01-01

    People sometimes solve problems with a unique process called insight, accompanied by an “Aha!” experience. It has long been unclear whether different cognitive and neural processes lead to insight versus noninsight solutions, or if solutions differ only in subsequent subjective feeling. Recent behavioral studies indicate distinct patterns of performance and suggest differential hemispheric involvement for insight and noninsight solutions. Subjects solved verbal problems, and after each correct solution indicated whether they solved with or without insight. We observed two objective neural correlates of insight. Functional magnetic resonance imaging (Experiment 1) revealed increased activity in the right hemisphere anterior superior temporal gyrus for insight relative to noninsight solutions. The same region was active during initial solving efforts. Scalp electroencephalogram recordings (Experiment 2) revealed a sudden burst of high-frequency (gamma-band) neural activity in the same area beginning 0.3 s prior to insight solutions. This right anterior temporal area is associated with making connections across distantly related information during comprehension. Although all problem solving relies on a largely shared cortical network, the sudden flash of insight occurs when solvers engage distinct neural and cognitive processes that allow them to see connections that previously eluded them. PMID:15094802

  16. SOX2 primes the epigenetic landscape in neural precursors enabling proper gene activation during hippocampal neurogenesis

    PubMed Central

    Amador-Arjona, Alejandro; Cimadamore, Flavio; Huang, Chun-Teng; Wright, Rebecca; Lewis, Susan; Gage, Fred H.; Terskikh, Alexey V.

    2015-01-01

    Newborn granule neurons generated from neural progenitor cells (NPCs) in the adult hippocampus play a key role in spatial learning and pattern separation. However, the molecular mechanisms that control activation of their neurogenic program remain poorly understood. Here, we report a novel function for the pluripotency factor sex-determining region Y (SRY)-related HMG box 2 (SOX2) in regulating the epigenetic landscape of poised genes activated at the onset of neuronal differentiation. We found that SOX2 binds to bivalently marked promoters of poised proneural genes [neurogenin 2 (Ngn2) and neurogenic differentiation 1 (NeuroD1)] and a subset of neurogenic genes [e.g., SRY-box 21 (Sox21), brain-derived neurotrophic factor (Bdnf), and growth arrest and DNA-damage–inducible, beta (Gadd45b)] where it functions to maintain the bivalent chromatin state by preventing excessive polycomb repressive complex 2 activity. Conditional ablation of SOX2 in adult hippocampal NPCs impaired the activation of proneural and neurogenic genes, resulting in increased neuroblast death and functionally aberrant newborn neurons. We propose that SOX2 sets a permissive epigenetic state in NPCs, thus enabling proper activation of the neuronal differentiation program under neurogenic cue. PMID:25825708

  17. Optical Modeling Activities for NASA's James Webb Space Telescope (JWST). 3; Wavefront Aberrations due to Alignment and Figure Compensation

    NASA Technical Reports Server (NTRS)

    Howard, Joseph

    2007-01-01

    This is part three of a series describing the ongoing optical modeling activities for James Webb Space Telescope (JWST). The first two discussed modeling JWST on-orbit performance using wavefront sensitivities to predict line of sight motion induced blur, and stability during thermal transients. The work here investigates the aberrations resulting from alignment and figure compensation of the controllable degrees of freedom (primary and secondary mirrors), which may be encountered during ground alignment and on-orbit commissioning of the observatory. The optical design of the telescope is a three-mirror anastigmat, with an active fold mirror at the exit pupil for fine guiding. The primary mirror is over 6.5 meters in diameter, and is composed of 18 hexagonal segments that can individually positioned on hexapods, as well as compensated for radius of curvature. This effectively gives both alignment and figure control of the primary mirror. The secondary mirror can be moved in rigid body only, giving alignment control of the telescope. The tertiary mirror is fixed, however, as well as the location of the science instrumentation. Simulations are performed of various combinations of active alignment corrections of component figure errors, and of primary mirror figure corrections of alignment errors. Single field point and moderate field knowledge is assumed in the corrections. Aberrations over the field are reported for the varying cases, and examples presented.

  18. Aberrant nuclear factor-kappa B activity in acute myeloid Leukemia: from molecular pathogenesis to therapeutic target

    PubMed Central

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-01-01

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade®), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  19. Aberrant nuclear factor-kappa B activity in acute myeloid leukemia: from molecular pathogenesis to therapeutic target.

    PubMed

    Zhou, Jianbiao; Ching, Ying Qing; Chng, Wee-Joo

    2015-03-20

    The overall survival of patients with acute myeloid leukemia (AML) has not been improved significantly over the last decade. Molecularly targeted agents hold promise to change the therapeutic landscape in AML. The nuclear factor kappa B (NF-κB) controls a plethora of biological process through switching on and off its long list of target genes. In AML, constitutive NF-κB has been detected in 40% of cases and its aberrant activity enable leukemia cells to evade apoptosis and stimulate proliferation. These facts suggest that NF-κB signaling pathway plays a fundamental role in the development of AML and it represents an attractive target for the intervention of AML. This review summarizes our current knowledge of NF-κB signaling transduction including canonical and non-canonical NF-κB pathways. Then we specifically highlight what factors contribute to the aberrant activation of NF-κB activity in AML, followed by an overview of 8 important clinical trials of the first FDA approved proteasome inhibitor, Bortezomib (Velcade), which is a NF-κB inhibitor too, in combination with other therapeutic agents in patients with AML. Finally, this review discusses the future directions of NF-κB inhibitor in treatment of AML, especially in targeting leukemia stem cells (LSCs). PMID:25823927

  20. Dynamic neural activity during stress signals resilient coping.

    PubMed

    Sinha, Rajita; Lacadie, Cheryl M; Constable, R Todd; Seo, Dongju

    2016-08-01

    Active coping underlies a healthy stress response, but neural processes supporting such resilient coping are not well-known. Using a brief, sustained exposure paradigm contrasting highly stressful, threatening, and violent stimuli versus nonaversive neutral visual stimuli in a functional magnetic resonance imaging (fMRI) study, we show significant subjective, physiologic, and endocrine increases and temporally related dynamically distinct patterns of neural activation in brain circuits underlying the stress response. First, stress-specific sustained increases in the amygdala, striatum, hypothalamus, midbrain, right insula, and right dorsolateral prefrontal cortex (DLPFC) regions supported the stress processing and reactivity circuit. Second, dynamic neural activation during stress versus neutral runs, showing early increases followed by later reduced activation in the ventrolateral prefrontal cortex (VLPFC), dorsal anterior cingulate cortex (dACC), left DLPFC, hippocampus, and left insula, suggested a stress adaptation response network. Finally, dynamic stress-specific mobilization of the ventromedial prefrontal cortex (VmPFC), marked by initial hypoactivity followed by increased VmPFC activation, pointed to the VmPFC as a key locus of the emotional and behavioral control network. Consistent with this finding, greater neural flexibility signals in the VmPFC during stress correlated with active coping ratings whereas lower dynamic activity in the VmPFC also predicted a higher level of maladaptive coping behaviors in real life, including binge alcohol intake, emotional eating, and frequency of arguments and fights. These findings demonstrate acute functional neuroplasticity during stress, with distinct and separable brain networks that underlie critical components of the stress response, and a specific role for VmPFC neuroflexibility in stress-resilient coping. PMID:27432990

  1. Early Interfaced Neural Activity from Chronic Amputated Nerves

    PubMed Central

    Garde, Kshitija; Keefer, Edward; Botterman, Barry; Galvan, Pedro; Romero, Mario I.

    2009-01-01

    Direct interfacing of transected peripheral nerves with advanced robotic prosthetic devices has been proposed as a strategy for achieving natural motor control and sensory perception of such bionic substitutes, thus fully functionally replacing missing limbs in amputees. Multi-electrode arrays placed in the brain and peripheral nerves have been used successfully to convey neural control of prosthetic devices to the user. However, reactive gliosis, micro hemorrhages, axonopathy and excessive inflammation currently limit their long-term use. Here we demonstrate that enticement of peripheral nerve regeneration through a non-obstructive multi-electrode array, after either acute or chronic nerve amputation, offers a viable alternative to obtain early neural recordings and to enhance long-term interfacing of nerve activity. Non-restrictive electrode arrays placed in the path of regenerating nerve fibers allowed the recording of action potentials as early as 8 days post-implantation with high signal-to-noise ratio, as long as 3 months in some animals, and with minimal inflammation at the nerve tissue-metal electrode interface. Our findings suggest that regenerative multi-electrode arrays of open design allow early and stable interfacing of neural activity from amputated peripheral nerves and might contribute towards conveying full neural control and sensory feedback to users of robotic prosthetic devices. PMID:19506704

  2. Application of neural networks to seismic active control

    SciTech Connect

    Tang, Yu

    1995-07-01

    An exploratory study on seismic active control using an artificial neural network (ANN) is presented in which a singledegree-of-freedom (SDF) structural system is controlled by a trained neural network. A feed-forward neural network and the backpropagation training method are used in the study. In backpropagation training, the learning rate is determined by ensuring the decrease of the error function at each training cycle. The training patterns for the neural net are generated randomly. Then, the trained ANN is used to compute the control force according to the control algorithm. The control strategy proposed herein is to apply the control force at every time step to destroy the build-up of the system response. The ground motions considered in the simulations are the N21E and N69W components of the Lake Hughes No. 12 record that occurred in the San Fernando Valley in California on February 9, 1971. Significant reduction of the structural response by one order of magnitude is observed. Also, it is shown that the proposed control strategy has the ability to reduce the peak that occurs during the first few cycles of the time history. These promising results assert the potential of applying ANNs to active structural control under seismic loads.

  3. Systematic fluctuation expansion for neural network activity equations

    PubMed Central

    Buice, Michael A.; Cowan, Jack D.; Chow, Carson C.

    2009-01-01

    Population rate or activity equations are the foundation of a common approach to modeling for neural networks. These equations provide mean field dynamics for the firing rate or activity of neurons within a network given some connectivity. The shortcoming of these equations is that they take into account only the average firing rate while leaving out higher order statistics like correlations between firing. A stochastic theory of neural networks which includes statistics at all orders was recently formulated. We describe how this theory yields a systematic extension to population rate equations by introducing equations for correlations and appropriate coupling terms. Each level of the approximation yields closed equations, i.e. they depend only upon the mean and specific correlations of interest, without an ad hoc criterion for doing so. We show in an example of an all-to-all connected network how our system of generalized activity equations captures phenomena missed by the mean field rate equations alone. PMID:19852585

  4. Dynamical criticality in the collective activity of a neural population

    NASA Astrophysics Data System (ADS)

    Mora, Thierry

    The past decade has seen a wealth of physiological data suggesting that neural networks may behave like critical branching processes. Concurrently, the collective activity of neurons has been studied using explicit mappings to classic statistical mechanics models such as disordered Ising models, allowing for the study of their thermodynamics, but these efforts have ignored the dynamical nature of neural activity. I will show how to reconcile these two approaches by learning effective statistical mechanics models of the full history of the collective activity of a neuron population directly from physiological data, treating time as an additional dimension. Applying this technique to multi-electrode recordings from retinal ganglion cells, and studying the thermodynamics of the inferred model, reveals a peak in specific heat reminiscent of a second-order phase transition.

  5. Optical modeling activities for NASA's James Webb Space Telescope (JWST): III. Wavefront aberrations due to alignment and figure compensation

    NASA Astrophysics Data System (ADS)

    Howard, Joseph M.

    2007-09-01

    This paper is part three of a series describing the ongoing optical modeling activities for the James Webb Space Telescope (JWST). The first two papers discussed modeling JWST on-orbit performance using wavefront sensitivities to predict line of sight motion induced blur, and stability during thermal transients [1-2]. The work here investigates the aberrations resulting from alignment and figure compensation of the controllable degrees of freedom (i.e. the primary and secondary mirrors), which may be encountered during ground alignment and on-orbit commissioning of the observatory. The optical design of the telescope is a three-mirror anastigmat, with an active fold mirror at the exit pupil for fine guiding. The primary mirror is over 6.5 meters in diameter, and is composed of 18 hexagonal segments that can individually positioned on hexapods, as well as compensated for radius of curvature. This architecture effectively gives both alignment and figure control of the primary mirror. The secondary mirror can be moved in rigid body only, and the tertiary mirror is fixed. Simulations are performed of various combinations of alignment and figure errors corrected by the primary and secondary mirrors. Single field point knowledge is assumed in the corrections, and aberrations over the field are reported for the varying cases.

  6. Epstein-Barr virus infection induces aberrant TLR activation pathway and fibroblast-myofibroblast conversion in scleroderma.

    PubMed

    Farina, Antonella; Cirone, Mara; York, Michael; Lenna, Stefania; Padilla, Cristina; McLaughlin, Sarah; Faggioni, Alberto; Lafyatis, Robert; Trojanowska, Maria; Farina, Giuseppina A

    2014-04-01

    Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, and fibrosis that mostly involve the skin and lungs. Epstein-Barr virus (EBV) is a lymphotropic γ-herpesvirus that has co-evolved with human species, infecting >95% of the adult population worldwide, and has been a leading candidate in triggering several autoimmune diseases. Here we show that EBV establishes infection in the majority of fibroblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV noncoding small RNAs (EBERs) and the increased expression of immediate-early lytic and latency mRNAs and proteins. We report that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate immune response in infected cells. EBV-Toll-like receptor (TLR) aberrant activation induces the expression of selected IFN-regulatory factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-β1 (TGFβ1), and several markers of fibroblast activation, such as smooth muscle actin and Endothelin-1, and all of these genes play a key role in determining the profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection occurring in mesenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis, and provide a unified disease mechanism represented by EBV reactivation. PMID:24129067

  7. Role of emergent neural activity in visual map development.

    PubMed

    Ackman, James B; Crair, Michael C

    2014-02-01

    The initial structural and functional development of visual circuits in reptiles, birds, and mammals happens independent of sensory experience. After eye opening, visual experience further refines and elaborates circuits that are critical for normal visual function. Innate genetic programs that code for gradients of molecules provide gross positional information for developing nerve cells, yet much of the cytoarchitectural complexity and synaptogenesis of neurons depends on calcium influx, neurotransmitter release, and neural activity before the onset of vision. In fact, specific spatiotemporal patterns of neural activity, or 'retinal waves', emerge amidst the development of the earliest connections made between excitable cells in the developing eye. These patterns of spontaneous activity, which have been observed in all amniote retinae examined to date, may be an evolved adaptation for species with long gestational periods before the onset of functional vision, imparting an informational robustness and redundancy to guide development of visual maps across the nervous system. Recent experiments indicate that retinal waves play a crucial role in the development of interconnections between different parts of the visual system, suggesting that these spontaneous patterns serve as a template-matching mechanism to prepare higher-order visually associative circuits for the onset of visuomotor learning and behavior. Key questions for future studies include determining the exact sources and nature of spontaneous activity during development, characterizing the interactions between neural activity and transcriptional gene regulation, and understanding the extent of circuit connectivity governed by retinal waves within and between sensory-motor systems. PMID:24492092

  8. Optogenetic feedback control of neural activity

    PubMed Central

    Newman, Jonathan P; Fong, Ming-fai; Millard, Daniel C; Whitmire, Clarissa J; Stanley, Garrett B; Potter, Steve M

    2015-01-01

    Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity. Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control, but no approach yet permits feedback control of neuronal firing. Here we present the ‘optoclamp’, a feedback control technology that provides continuous, real-time adjustments of bidirectional optical stimulation in order to lock spiking activity at specified targets over timescales ranging from seconds to days. We demonstrate how this system can be used to decouple neuronal firing levels from ongoing changes in network excitability due to multi-hour periods of glutamatergic or GABAergic neurotransmission blockade in vitro as well as impinging vibrissal sensory drive in vivo. This technology enables continuous, precise optical control of firing in neuronal populations in order to disentangle causally related variables of circuit activation in a physiologically and ethologically relevant manner. DOI: http://dx.doi.org/10.7554/eLife.07192.001 PMID:26140329

  9. Monitoring activity in neural circuits with genetically encoded indicators

    PubMed Central

    Broussard, Gerard J.; Liang, Ruqiang; Tian, Lin

    2014-01-01

    Recent developments in genetically encoded indicators of neural activity (GINAs) have greatly advanced the field of systems neuroscience. As they are encoded by DNA, GINAs can be targeted to genetically defined cellular populations. Combined with fluorescence microscopy, most notably multi-photon imaging, GINAs allow chronic simultaneous optical recordings from large populations of neurons or glial cells in awake, behaving mammals, particularly rodents. This large-scale recording of neural activity at multiple temporal and spatial scales has greatly advanced our understanding of the dynamics of neural circuitry underlying behavior—a critical first step toward understanding the complexities of brain function, such as sensorimotor integration and learning. Here, we summarize the recent development and applications of the major classes of GINAs. In particular, we take an in-depth look at the design of available GINA families with a particular focus on genetically encoded calcium indicators (GCaMPs), sensors probing synaptic activity, and genetically encoded voltage indicators. Using the family of the GCaMP as an example, we review established sensor optimization pipelines. We also discuss practical considerations for end users of GINAs about experimental methods including approaches for gene delivery, imaging system requirements, and data analysis techniques. With the growing toolbox of GINAs and with new microscopy techniques pushing beyond their current limits, the age of light can finally achieve the goal of broad and dense sampling of neuronal activity across time and brain structures to obtain a dynamic picture of brain function. PMID:25538558

  10. The effects of gratitude expression on neural activity.

    PubMed

    Kini, Prathik; Wong, Joel; McInnis, Sydney; Gabana, Nicole; Brown, Joshua W

    2016-03-01

    Gratitude is a common aspect of social interaction, yet relatively little is known about the neural bases of gratitude expression, nor how gratitude expression may lead to longer-term effects on brain activity. To address these twin issues, we recruited subjects who coincidentally were entering psychotherapy for depression and/or anxiety. One group participated in a gratitude writing intervention, which required them to write letters expressing gratitude. The therapy-as-usual control group did not perform a writing intervention. After three months, subjects performed a "Pay It Forward" task in the fMRI scanner. In the task, subjects were repeatedly endowed with a monetary gift and then asked to pass it on to a charitable cause to the extent they felt grateful for the gift. Operationalizing gratitude as monetary gifts allowed us to engage the subjects and quantify the gratitude expression for subsequent analyses. We measured brain activity and found regions where activity correlated with self-reported gratitude experience during the task, even including related constructs such as guilt motivation and desire to help as statistical controls. These were mostly distinct from brain regions activated by empathy or theory of mind. Also, our between groups cross-sectional study found that a simple gratitude writing intervention was associated with significantly greater and lasting neural sensitivity to gratitude - subjects who participated in gratitude letter writing showed both behavioral increases in gratitude and significantly greater neural modulation by gratitude in the medial prefrontal cortex three months later. PMID:26746580

  11. Persistent Activity in Neural Networks with Dynamic Synapses

    PubMed Central

    Barak, Omri; Tsodyks, Misha

    2007-01-01

    Persistent activity states (attractors), observed in several neocortical areas after the removal of a sensory stimulus, are believed to be the neuronal basis of working memory. One of the possible mechanisms that can underlie persistent activity is recurrent excitation mediated by intracortical synaptic connections. A recent experimental study revealed that connections between pyramidal cells in prefrontal cortex exhibit various degrees of synaptic depression and facilitation. Here we analyze the effect of synaptic dynamics on the emergence and persistence of attractor states in interconnected neural networks. We show that different combinations of synaptic depression and facilitation result in qualitatively different network dynamics with respect to the emergence of the attractor states. This analysis raises the possibility that the framework of attractor neural networks can be extended to represent time-dependent stimuli. PMID:17319739

  12. MAGNETIC LIQUID DEFORMABLE MIRRORS FOR ASTRONOMICAL APPLICATIONS: ACTIVE CORRECTION OF OPTICAL ABERRATIONS FROM LOWER-GRADE OPTICS AND SUPPORT SYSTEM

    SciTech Connect

    Borra, E. F.

    2012-08-01

    Deformable mirrors are increasingly used in astronomy. However, they still are limited in stroke for active correction of high-amplitude optical aberrations. Magnetic liquid deformable mirrors (MLDMs) are a new technology that has the advantages of high-amplitude deformations and low costs. In this paper, we demonstrate extremely high strokes and interactuator strokes achievable by MLDMs which can be used in astronomical instrumentation. In particular, we consider the use of such a mirror to suggest an interesting application for the next generation of large telescopes. We present a prototype 91 actuator deformable mirror made of a magnetic liquid (ferrofluid). This mirror uses a technique that linearizes the response of such mirrors by superimposing a large and uniform magnetic field on the magnetic field produced by an array of small coils. We discuss experimental results that illustrate the performance of MLDMs. A most interesting application of MLDMs comes from the fact they could be used to correct the aberrations of large and lower optical quality primary mirrors held by simple support systems. We estimate basic parameters of the needed MLDMs, obtaining reasonable values.

  13. Curvaceous female bodies activate neural reward centers in men

    PubMed Central

    Spicer, Kristen Rae

    2010-01-01

    Facial symmetry, masculinity and shoulder-to-hip ratios in men convey information to mates about reproductive/genetic quality, the so-called “good genes” hypothesis. On the other hand waist-to-hip ratio conveys important reproductive information about women to men. Here using fMRI, men showed activation in neural reward centers when they viewed and rated the attractiveness of surgically optimally configured female bodies. PMID:20714414

  14. Internal models for interpreting neural population activity during sensorimotor control

    PubMed Central

    Golub, Matthew D; Yu, Byron M; Chase, Steven M

    2015-01-01

    To successfully guide limb movements, the brain takes in sensory information about the limb, internally tracks the state of the limb, and produces appropriate motor commands. It is widely believed that this process uses an internal model, which describes our prior beliefs about how the limb responds to motor commands. Here, we leveraged a brain-machine interface (BMI) paradigm in rhesus monkeys and novel statistical analyses of neural population activity to gain insight into moment-by-moment internal model computations. We discovered that a mismatch between subjects’ internal models and the actual BMI explains roughly 65% of movement errors, as well as long-standing deficiencies in BMI speed control. We then used the internal models to characterize how the neural population activity changes during BMI learning. More broadly, this work provides an approach for interpreting neural population activity in the context of how prior beliefs guide the transformation of sensory input to motor output. DOI: http://dx.doi.org/10.7554/eLife.10015.001 PMID:26646183

  15. Efficient Universal Computing Architectures for Decoding Neural Activity

    PubMed Central

    Rapoport, Benjamin I.; Turicchia, Lorenzo; Wattanapanitch, Woradorn; Davidson, Thomas J.; Sarpeshkar, Rahul

    2012-01-01

    The ability to decode neural activity into meaningful control signals for prosthetic devices is critical to the development of clinically useful brain– machine interfaces (BMIs). Such systems require input from tens to hundreds of brain-implanted recording electrodes in order to deliver robust and accurate performance; in serving that primary function they should also minimize power dissipation in order to avoid damaging neural tissue; and they should transmit data wirelessly in order to minimize the risk of infection associated with chronic, transcutaneous implants. Electronic architectures for brain– machine interfaces must therefore minimize size and power consumption, while maximizing the ability to compress data to be transmitted over limited-bandwidth wireless channels. Here we present a system of extremely low computational complexity, designed for real-time decoding of neural signals, and suited for highly scalable implantable systems. Our programmable architecture is an explicit implementation of a universal computing machine emulating the dynamics of a network of integrate-and-fire neurons; it requires no arithmetic operations except for counting, and decodes neural signals using only computationally inexpensive logic operations. The simplicity of this architecture does not compromise its ability to compress raw neural data by factors greater than . We describe a set of decoding algorithms based on this computational architecture, one designed to operate within an implanted system, minimizing its power consumption and data transmission bandwidth; and a complementary set of algorithms for learning, programming the decoder, and postprocessing the decoded output, designed to operate in an external, nonimplanted unit. The implementation of the implantable portion is estimated to require fewer than 5000 operations per second. A proof-of-concept, 32-channel field-programmable gate array (FPGA) implementation of this portion is consequently energy efficient

  16. Reduced neural activity of the prefrontal cognitive control circuitry during response inhibition to negative words in people with schizophrenia

    PubMed Central

    Vercammen, Ans; Morris, Richard; Green, Melissa J.; Lenroot, Rhoshel; Kulkarni, Jayashri; Carr, Vaughan J.; Weickert, Cynthia Shannon; Weickert, Thomas W.

    2012-01-01

    Background Schizophrenia is characterized by deficits in executive control and impairments in emotion processing. This study assessed the nature and extent of potential alterations in the neural substrates supporting the interaction between cognitive control mechanisms and emotion attribution processes in people with schizophrenia. Methods Functional magnetic resonance imaging was performed during a verbal emotional go/no-go task. People with schizophrenia and healthy controls responded to word stimuli of a prespecified emotional valence (positive, negative or neutral) while inhibiting responses to stimuli of a different valence. Results We enrolled 20 people with schizophrenia and 23 controls in the study. Healthy controls activated an extensive dorsal prefrontal–parietal network while inhibiting responses to negative words compared to neutral words, but showed deactivation of the midcingulate cortex while inhibiting responses to positive words compared to neutral words. People with schizophrenia failed to activate this network during response inhibition to negative words, whereas during response inhibition to positive words they did not deactivate the cingulate, but showed increased responsivity in the frontal cortex. Limitations Sample heterogeneity is characteristic of studies of schizophrenia and may have contributed to more variable neural responses in the patient sample despite the care taken to control for potentially confounding variables. Conclusion Our results showed that schizophrenia is associated with aberrant modulation of neural responses during the interaction between cognitive control and emotion processing. Failure of the frontal circuitry to regulate goal-directed behaviour based on emotion attributions may contribute to deficits in psychosocial functioning in daily life. PMID:22617625

  17. Can Neural Activity Propagate by Endogenous Electrical Field?

    PubMed Central

    Qiu, Chen; Shivacharan, Rajat S.; Zhang, Mingming

    2015-01-01

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2–6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5–5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds. SIGNIFICANCE STATEMENT Neural activity (waves or spikes) can propagate using well documented mechanisms such as synaptic transmission, gap junctions, or diffusion. However, the purpose of this paper is to provide an explanation for experimental data showing that neural signals can propagate by means other than synaptic

  18. The Generation Effect: Activating Broad Neural Circuits During Memory Encoding

    PubMed Central

    Rosner, Zachary A.; Elman, Jeremy A.; Shimamura, Arthur P.

    2012-01-01

    The generation effect is a robust memory phenomenon in which actively producing material during encoding acts to improve later memory performance. In an fMRI analysis, we explored the neural basis of this effect. During encoding, participants generated synonyms from word-fragment cues (e.g. GARBAGE-W_ST_) or read other synonym pairs (e.g. GARBAGE-WASTE). Compared to simply reading target words, generating target words significantly improved later recognition memory performance. During encoding, this benefit was associated with a broad neural network that involved both prefrontal (inferior frontal gyrus, middle frontal gyrus) and posterior cortex (inferior temporal gyrus, lateral occipital cortex, parahippocampal gyrus, ventral posterior parietal cortex). These findings define the prefrontal-posterior cortical dynamics associated with the mnemonic benefits underlying the generation effect. PMID:23079490

  19. Detection of interplanetary activity using artificial neural networks

    NASA Astrophysics Data System (ADS)

    Gothoskar, Pradeep; Khobragade, Shyam

    1995-12-01

    Early detection of interplanetary activity is important when attempting to associate, with better accuracy, interplanetary phenomena with solar activity and geomagnetic disturbances. However, for a large number of interplanetary observations to be done every day, extensive data analysis is required, leading to a delay in the detection of transient interplanetary activity. In particular, the interplanetary scintillation (IPS) observations done with Ooty Radio Telescope (ORT) need extensive human effort to reduce the data and to model, often subjectively, the scintillation power spectra. We have implemented an artificial neural network (ANN) to detect interplanetary activity using the power spectrum scintillation. The ANN was trained to detect the disturbed power spectra, used as an indicator of the interplanetary activity, and to recognize normal and strong scattering spectra from a large data base of IPS spectra. The coincidence efficiency of classification by the network compared with the experts' judgement to detect the normal, disturbed and strong scattering spectra was found to be greater than 80 per cent. The neural network, when applied during the IPS mapping programme to provide early indication of interplanetary activity, would significantly help the ongoing efforts to predict geomagnetic disturbances.

  20. A neural network model for olfactory glomerular activity prediction

    NASA Astrophysics Data System (ADS)

    Soh, Zu; Tsuji, Toshio; Takiguchi, Noboru; Ohtake, Hisao

    2012-12-01

    Recently, the importance of odors and methods for their evaluation have seen increased emphasis, especially in the fragrance and food industries. Although odors can be characterized by their odorant components, their chemical information cannot be directly related to the flavors we perceive. Biological research has revealed that neuronal activity related to glomeruli (which form part of the olfactory system) is closely connected to odor qualities. Here we report on a neural network model of the olfactory system that can predict glomerular activity from odorant molecule structures. We also report on the learning and prediction ability of the proposed model.

  1. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis.

    PubMed

    Kasischke, Karl A; Vishwasrao, Harshad D; Fisher, Patricia J; Zipfel, Warren R; Webb, Watt W

    2004-07-01

    We have found that two-photon fluorescence imaging of nicotinamide adenine dinucleotide (NADH) provides the sensitivity and spatial three-dimensional resolution to resolve metabolic signatures in processes of astrocytes and neurons deep in highly scattering brain tissue slices. This functional imaging reveals spatiotemporal partitioning of glycolytic and oxidative metabolism between astrocytes and neurons during focal neural activity that establishes a unifying hypothesis for neurometabolic coupling in which early oxidative metabolism in neurons is eventually sustained by late activation of the astrocyte-neuron lactate shuttle. Our model integrates existing views of brain energy metabolism and is in accord with known macroscopic physiological changes in vivo. PMID:15232110

  2. Activation of mutant protein kinase C{gamma} leads to aberrant sequestration and impairment of its cellular function

    SciTech Connect

    Doran, Graeme; Davies, Kay E.; Talbot, Kevin

    2008-08-01

    Mutations in protein kinase C{gamma} (PKC{gamma}) cause the neurodegenerative disease spinocerebellar ataxia type 14 (SCA14). In this study, expression of an extensive panel of known SCA14-associated PKC{gamma} mutations as fusion proteins in cell culture led to the consistent formation of cytoplasmic aggregates in response to purinoceptor stimulation. Aggregates co-stained with antibodies to phosphorylated PKC{gamma} and the early endosome marker EEA1 but failed to redistribute to the cell membrane under conditions of oxidative stress. These studies suggest that Purkinje cell damage in SCA14 may result from a reduction of PKC{gamma} activity due its aberrant sequestration in the early endosome compartment.

  3. Aberrant activation of Wnt/β-catenin signaling pathway contributes to the sequential progression of DMBA-induced HBP carcinomas.

    PubMed

    Vidya Priyadarsini, Ramamurthi; Senthil Murugan, Ramalingam; Nagini, Siddavaram

    2012-01-01

    Wnt signaling pathway mediated via interactions between β-catenin and members of the TCF/LEF-1 family of transcription factors plays a central role in the regulation of epithelial cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition, and invasion. Aberrant activation of the Wnt/β-catenin signaling pathway with overexpression of Wnt and Fz, mutations of APC, β-catenin, and axin 1, and cytoplasmic accumulation of β-catenin have been frequently reported in a broad spectrum of human malignancies including oral squamous cell carcinomas (OSCCs). However, changes in the components of the Wnt signaling pathway have not been documented during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis, a paradigm for oral oncogenesis and chemointervention. In this study, we evaluated the role of β-catenin accumulation and Wnt ligands, Wnt signaling members (Fz, Dvl, APC, GSK-3β, axin, and WIF) and the downstream targets of Wnt (cyclin D1, MMP-2, and MMP-9) during the sequential progression of DMBA-induced HBP carcinomas by semi-quantitative RT-PCR and western blot analyses. Our data reveal a correlation between β-catenin accumulation and activation of Wnt signaling, and its downstream effector molecules during the sequential development of HBP carcinomas from hyperplasia to invasive carcinoma through dysplasia. Our data also support a pivotal role for β-catenin in the malignant transition of the HBP. Aberrant Wnt signaling may be a hallmark of progression to malignancy during DMBA-induced HBP carcinogenesis and could be a potential preventive and therapeutic target for suppression of OSCC. PMID:21924667

  4. ERα propelled aberrant global DNA hypermethylation by activating the DNMT1 gene to enhance anticancer drug resistance in human breast cancer cells

    PubMed Central

    Lv, Jinghuan; Ding, Haijian; Zhang, Xin A.; Shao, Lipei; Yang, Nan; Cheng, He; Sun, Luan; Zhu, Dongliang; Yang, Yin; Li, Andi; Han, Xiao; Sun, Yujie

    2016-01-01

    Drug-induced aberrant DNA methylation is the first identified epigenetic marker involved in chemotherapy resistance. Understanding how the aberrant DNA methylation is acquired would impact cancer treatment in theory and practice. In this study we systematically investigated whether and how ERα propelled aberrant global DNA hypermethylation in the context of breast cancer drug resistance. Our data demonstrated that anticancer drug paclitaxel (PTX) augmented ERα binding to the DNMT1 and DNMT3b promoters to activate DNMT1 and DNMT3b genes, enhancing the PTX resistance of breast cancer cells. In support of these observations, estrogen enhanced multi-drug resistance of breast cancer cells by up-regulation of DNMT1 and DNMT3b genes. Nevertheless, the aberrant global DNA hypermethylation was dominantly induced by ERα-activated-DNMT1, since DNMT1 over-expression significantly increased global DNA methylation and DNMT1 knockdown reversed the ERα-induced global DNA methylation. Altering DNMT3b expression had no detectable effect on global DNA methylation. Consistently, the expression level of DNMT1 was positively correlated with ERα in 78 breast cancer tissue samples shown by our immunohistochemistry (IHC) analysis and negatively correlated with relapse-free survival (RFS) and distance metastasis-free survival (DMFS) of ERα-positive breast cancer patients. This study provides a new perspective for understanding the mechanism underlying drug-resistance-facilitating aberrant DNA methylation in breast cancer and other estrogen dependent tumors. PMID:26980709

  5. Inference of other's internal neural models from active observation.

    PubMed

    Kim, Kyung-Joong; Cho, Sung-Bae

    2015-02-01

    Recently, there have been several attempts to replicate theory of mind, which explains how humans infer the mental states of other people using multiple sensory input, with artificial systems. One example of this is a robot that observes the behavior of other artificial systems and infers their internal models, mapping sensory inputs to the actuator's control signals. In this paper, we present the internal model as an artificial neural network, similar to biological systems. During inference, an observer can use an active incremental learning algorithm to guess an actor's internal neural model. This could significantly reduce the effort needed to guess other people's internal models. We apply an algorithm to the actor-observer robot scenarios with/without prior knowledge of the internal models. To validate our approach, we use a physics-based simulator with virtual robots. A series of experiments reveal that the observer robot can construct an "other's self-model", validating the possibility that a neural-based approach can be used as a platform for learning cognitive functions. PMID:25617791

  6. Aberrant glomerular filtration of urokinase-type plasminogen activator in nephrotic syndrome leads to amiloride-sensitive plasminogen activation in urine.

    PubMed

    Stæhr, Mette; Buhl, Kristian B; Andersen, René F; Svenningsen, Per; Nielsen, Flemming; Hinrichs, Gitte Rye; Bistrup, Claus; Jensen, Boye L

    2015-08-01

    In nephrotic syndrome, aberrant glomerular filtration of plasminogen and conversion to active plasmin in preurine are thought to activate proteolytically epithelial sodium channel (ENaC) and contribute to sodium retention and edema. The ENaC blocker amiloride is an off-target inhibitor of urokinase-type plasminogen activator (uPA) in vitro. It was hypothesized that uPA is abnormally filtered to preurine and is inhibited in urine by amiloride in nephrotic syndrome. This was tested by determination of Na(+) balance, uPA protein and activity, and amiloride concentration in urine from rats with puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Urine samples from 6 adult and 18 pediatric patients with nephrotic syndrome were analyzed for uPA activity and protein. PAN treatment induced significant proteinuria in rats which coincided with increased urine uPA protein and activity, increased urine protease activity, and total plasminogen/plasmin concentration and Na(+) retention. Amiloride (2 mg·kg(-1)·24 h(-1)) concentration in urine was in the range 10-20 μmol/l and reduced significantly urine uPA activity, plasminogen activation, protease activity, and sodium retention in PAN rats, while proteinuria was not altered. In paired urine samples, uPA protein was significantly elevated in urine from children with active nephrotic syndrome compared with remission phase. In six adult nephrotic patients, urine uPA protein and activity correlated positively with 24 h urine protein excretion. In conclusion, nephrotic syndrome is associated with aberrant filtration of uPA across the injured glomerular barrier. Amiloride inhibits urine uPA activity which attenuates plasminogen activation and urine protease activity in vivo. Urine uPA is a relevant target for amiloride in vivo. PMID:25972510

  7. Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

    PubMed Central

    Peterson, EJ; Tyler, DJ

    2014-01-01

    Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923

  8. Motor neuron activation in peripheral nerves using infrared neural stimulation

    NASA Astrophysics Data System (ADS)

    Peterson, E. J.; Tyler, D. J.

    2014-02-01

    Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

  9. Infrared neural stimulation fails to evoke neural activity in the deaf guinea pig cochlea.

    PubMed

    Thompson, Alexander C; Fallon, James B; Wise, Andrew K; Wade, Scott A; Shepherd, Robert K; Stoddart, Paul R

    2015-06-01

    At present there is some debate as to the processes by which infrared neural stimulation (INS) activates neurons in the cochlea, as the lasers used for INS can potentially generate a range of secondary stimuli e.g. an acoustic stimulus is produced when the light is absorbed by water. To clarify whether INS in the cochlea requires functioning hair cells and to explore the potential relevance to cochlear implants, experiments using INS were performed in the cochleae of both normal hearing and profoundly deaf guinea pigs. A response to laser stimulation was readily evoked in normal hearing cochlea. However, no response was evoked in any profoundly deaf cochleae, for either acute or chronic deafening, contrary to previous work where a response was observed after acute deafening with ototoxic drugs. A neural response to electrical stimulation was readily evoked in all cochleae after deafening. The absence of a response from optical stimuli in profoundly deaf cochleae suggests that the response from INS in the cochlea is hair cell mediated. PMID:25796297

  10. Increased neural activity during overt and continuous semantic verbal fluency in major depression: mainly a failure to deactivate.

    PubMed

    Backes, Heidelore; Dietsche, Bruno; Nagels, Arne; Stratmann, Mirjam; Konrad, Carsten; Kircher, Tilo; Krug, Axel

    2014-10-01

    Major depression is associated with impairments in semantic verbal fluency (VF). However, the neural correlates underlying dysfunctional cognitive processing in depressed subjects during the production of semantic category members still remain unclear. In the current study, an overt and continuous semantic VF paradigm was used to examine these mechanisms in a representative sample of 33 patients diagnosed with a current episode of unipolar depression and 33 statistically matched healthy controls. Subjects articulated words in response to semantic category cues while brain activity was measured with functional magnetic resonance imaging (fMRI). Compared to controls, patients showed poorer task performance. On the neural level, a group by condition interaction analysis, corrected for task performance, revealed a reduced task-related deactivation in patients in the right parahippocampal gyrus, the right fusiform gyrus, and the right supplementary motor area. An additional and an increased task-related activation in patients were observed in the right precentral gyrus and the left cerebellum, respectively. These results indicate that a failure to suppress potentially interfering activity from inferior temporal regions involved in default-mode network functions and visual imagery, accompanied by an enhanced recruitment of areas implicated in speech initiation and higher-order language processes, may underlie dysfunctional cognitive processing during semantic VF in depression. The finding that patients with depression demonstrated both decreased performance and aberrant brain activation during the current semantic VF task demonstrates that this paradigm is a sensitive tool for assessing brain dysfunctions in clinical populations. PMID:24557502

  11. Supervised learning for neural manifold using spatiotemporal brain activity

    NASA Astrophysics Data System (ADS)

    Kuo, Po-Chih; Chen, Yong-Sheng; Chen, Li-Fen

    2015-12-01

    Objective. Determining the means by which perceived stimuli are compactly represented in the human brain is a difficult task. This study aimed to develop techniques for the construction of the neural manifold as a representation of visual stimuli. Approach. We propose a supervised locally linear embedding method to construct the embedded manifold from brain activity, taking into account similarities between corresponding stimuli. In our experiments, photographic portraits were used as visual stimuli and brain activity was calculated from magnetoencephalographic data using a source localization method. Main results. The results of 10 × 10-fold cross-validation revealed a strong correlation between manifolds of brain activity and the orientation of faces in the presented images, suggesting that high-level information related to image content can be revealed in the brain responses represented in the manifold. Significance. Our experiments demonstrate that the proposed method is applicable to investigation into the inherent patterns of brain activity.

  12. Tools for Resolving Functional Activity and Connectivity within Intact Neural Circuits

    PubMed Central

    Jennings, Joshua H.; Stuber, Garret D.

    2014-01-01

    Mammalian neural circuits are sophisticated biological systems that choreograph behavioral processes vital for survival. While the inherent complexity of discrete neural circuits has proven difficult to decipher, many parallel methodological developments promise to help delineate the function and connectivity of molecularly defined neural circuits. Here, we review recent technological advances designed to precisely monitor and manipulate neural circuit activity. We propose a holistic, multifaceted approach for unraveling how behavioral states are manifested through the cooperative interactions between discrete neurocircuit elements. PMID:24405680

  13. Neural activities during affective processing in people with Alzheimer's disease.

    PubMed

    Lee, Tatia M C; Sun, Delin; Leung, Mei-Kei; Chu, Leung-Wing; Keysers, Christian

    2013-03-01

    This study examined brain activities in people with Alzheimer's disease when viewing happy, sad, and fearful facial expressions of others. A functional magnetic resonance imaging and a voxel-based morphometry methodology together with a passive viewing of emotional faces paradigm were employed to compare the affective processing in 12 people with mild Alzheimer's disease and 12 matched controls. The main finding was that the clinical participants showed reduced activations in regions associated with the motor simulation system (the ventral premotor cortex) and in regions associated with emotional simulation-empathy (the anterior insula and adjacent frontal operculum). This regional decline in blood oxygen level-dependent signals appeared to be lateralized in the left hemisphere and was not related to any structural degeneration in the clinical participants. Furthermore, the regions that showed changes in neural activity differed for the 3 emotional facial expressions studied. Findings of our study indicate that neural changes in regions associated with the motor and emotional simulation systems might play an important role in the development of Alzheimer's disease. PMID:22840336

  14. Multifractal detrended fluctuation analysis of optogenetic modulation of neural activity

    NASA Astrophysics Data System (ADS)

    Kumar, S.; Gu, L.; Ghosh, N.; Mohanty, S. K.

    2013-02-01

    Here, we introduce a computational procedure to examine whether optogenetically activated neuronal firing recordings could be characterized as multifractal series. Optogenetics is emerging as a valuable experimental tool and a promising approach for studying a variety of neurological disorders in animal models. The spiking patterns from cortical region of the brain of optogenetically-stimulated transgenic mice were analyzed using a sophisticated fluctuation analysis method known as multifractal detrended fluctuation analysis (MFDFA). We observed that the optogenetically-stimulated neural firings are consistent with a multifractal process. Further, we used MFDFA to monitor the effect of chemically induced pain (formalin injection) and optogenetic treatment used to relieve the pain. In this case, dramatic changes in parameters characterizing a multifractal series were observed. Both the generalized Hurst exponent and width of singularity spectrum effectively differentiates the neural activities during control and pain induction phases. The quantitative nature of the analysis equips us with better measures to quantify pain. Further, it provided a measure for effectiveness of the optogenetic stimulation in inhibiting pain. MFDFA-analysis of spiking data from other deep regions of the brain also turned out to be multifractal in nature, with subtle differences in the parameters during pain-induction by formalin injection and inhibition by optogenetic stimulation. Characterization of neuronal firing patterns using MFDFA will lead to better understanding of neuronal response to optogenetic activation and overall circuitry involved in the process.

  15. Classification of the extracellular fields produced by activated neural structures

    PubMed Central

    Richerson, Samantha; Ingram, Mark; Perry, Danielle; Stecker, Mark M

    2005-01-01

    Background Classifying the types of extracellular potentials recorded when neural structures are activated is an important component in understanding nerve pathophysiology. Varying definitions and approaches to understanding the factors that influence the potentials recorded during neural activity have made this issue complex. Methods In this article, many of the factors which influence the distribution of electric potential produced by a traveling action potential are discussed from a theoretical standpoint with illustrative simulations. Results For an axon of arbitrary shape, it is shown that a quadrupolar potential is generated by action potentials traveling along a straight axon. However, a dipole moment is generated at any point where an axon bends or its diameter changes. Next, it is shown how asymmetric disturbances in the conductivity of the medium surrounding an axon produce dipolar potentials, even during propagation along a straight axon. Next, by studying the electric fields generated by a dipole source in an insulating cylinder, it is shown that in finite volume conductors, the extracellular potentials can be very different from those in infinite volume conductors. Finally, the effects of impulses propagating along axons with inhomogeneous cable properties are analyzed. Conclusion Because of the well-defined factors affecting extracellular potentials, the vague terms far-field and near-field potentials should be abandoned in favor of more accurate descriptions of the potentials. PMID:16146569

  16. Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome.

    PubMed

    Tan, Hong Yien; Yong, Yean Kong; Shankar, Esaki M; Paukovics, Geza; Ellegård, Rada; Larsson, Marie; Kamarulzaman, Adeeba; French, Martyn A; Crowe, Suzanne M

    2016-05-15

    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS. PMID:27076678

  17. Temperature systematically modifies neural activity for sweet taste

    PubMed Central

    Wilson, David M.

    2014-01-01

    Temperature can modify neural and behavioral responses to taste stimuli that elicit “sweetness,” a perception linked to intake of calorie-laden foods. However, the role of temperature in the neural representation of sweet taste is poorly understood. Here we made electrophysiological recordings from gustatory neurons in the medulla of inbred mice to study how adjustments in taste solution temperature to cool (18°C), ambient (22°C), and warm (30°C and 37°C) values changed the magnitude and latency of gustatory activity to sucrose (0, 0.05, 0.1, 0.17, 0.31, and 0.56 M). Analysis of 22 sucrose-best neurons revealed that temperature markedly influenced responses to sucrose, which, across concentrations, were largest when solutions were warmed to 30°C. However, reducing solution temperature from warm to ambient to cool progressively steepened the slope of the sucrose concentration-response function computed across cells (P < 0.05), indicating that mean activity to sucrose increased more rapidly with concentration steps under cooling than with warming. Thus the slope of the sucrose concentration-response function shows an inverse relation with temperature. Temperature also influenced latency to the first spike of the sucrose response. Across neurons, latencies were shorter when sucrose solutions were warmed and longer, by hundreds of milliseconds, when solutions were cooled (P < 0.05), indicating that temperature is also a temporal parameter of sucrose activity. Our findings reveal that temperature systematically modifies the timing of gustatory activity to sucrose in the mammalian brain and how this activity changes with concentration. Results further highlight how oral somatosensory cues function as physiological modulators of gustatory processing. PMID:24966301

  18. Fast calcium sensor proteins for monitoring neural activity

    PubMed Central

    Badura, Aleksandra; Sun, Xiaonan Richard; Giovannucci, Andrea; Lynch, Laura A.; Wang, Samuel S.-H.

    2014-01-01

    Abstract. A major goal of the BRAIN Initiative is the development of technologies to monitor neuronal network activity during active information processing. Toward this goal, genetically encoded calcium indicator proteins have become widely used for reporting activity in preparations ranging from invertebrates to awake mammals. However, slow response times, the narrow sensitivity range of Ca2+ and in some cases, poor signal-to-noise ratio still limit their usefulness. Here, we review recent improvements in the field of neural activity-sensitive probe design with a focus on the GCaMP family of calcium indicator proteins. In this context, we present our newly developed Fast-GCaMPs, which have up to 4-fold accelerated off-responses compared with the next-fastest GCaMP, GCaMP6f. Fast-GCaMPs were designed by destabilizing the association of the hydrophobic pocket of calcium-bound calmodulin with the RS20 binding domain, an intramolecular interaction that protects the green fluorescent protein chromophore. Fast-GCaMP6f-RS06 and Fast-GCaMP6f-RS09 have rapid off-responses in stopped-flow fluorimetry, in neocortical brain slices, and in the intact cerebellum in vivo. Fast-GCaMP6f variants should be useful for tracking action potentials closely spaced in time, and for following neural activity in fast-changing compartments, such as axons and dendrites. Finally, we discuss strategies that may allow tracking of a wider range of neuronal firing rates and improve spike detection. PMID:25558464

  19. Visualization and Manipulation of Neural Activity in the Developing Vertebrate Nervous System

    PubMed Central

    Zhang, Jiayi; Ackman, James B.; Dhande, Onkar S.; Crair, Michael C.

    2011-01-01

    Neural activity during vertebrate development has been unambiguously shown to play a critical role in sculpting circuit formation and function. Patterned neural activity in various parts of the developing nervous system is thought to modulate neurite outgrowth, axon targeting, and synapse refinement. The nature and role of patterned neural activity during development has been classically studied with in vitro preparations using pharmacological manipulations. In this review we discuss newly available and developing molecular–genetic tools for the visualization and manipulation of neural activity patterns specifically during development. PMID:22121343

  20. Conditions of activity bubble uniqueness in dynamic neural fields.

    PubMed

    Mikhailova, Inna; Goerick, Christian

    2005-02-01

    Dynamic neural fields (DNFs) offer a rich spectrum of dynamic properties like hysteresis, spatiotemporal information integration, and coexistence of multiple attractors. These properties make DNFs more and more popular in implementations of sensorimotor loops for autonomous systems. Applications often imply that DNFs should have only one compact region of firing neurons (activity bubble), whereas the rest of the field should not fire (e.g., if the field represents motor commands). In this article we prove the conditions of activity bubble uniqueness in the case of locally symmetric input bubbles. The qualitative condition on inhomogeneous inputs used in earlier work on DNFs is transfered to a quantitative condition of a balance between the internal dynamics and the input. The mathematical analysis is carried out for the two-dimensional case with methods that can be extended to more than two dimensions. The article concludes with an example of how our theoretical results facilitate the practical use of DNFs. PMID:15685393

  1. Prediction of Visual Acuity from Wavefront Aberrations

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B. (Inventor); Ahumada, Albert J. (Inventor)

    2013-01-01

    A method for generating a visual acuity metric, based on wavefront aberrations (WFAs), associated with a test subject and representing classes of imperfections, such as defocus, astigmatism, coma and spherical aberrations, of the subject's visual system. The metric allows choices of different image template, can predict acuity for different target probabilities, can incorporate different and possibly subject-specific neural transfer functions, can predict acuity for different subject templates, and incorporates a model of the optotype identification task.

  2. Independent Components of Neural Activity Carry Information on Individual Populations

    PubMed Central

    Głąbska, Helena; Potworowski, Jan; Łęski, Szymon; Wójcik, Daniel K.

    2014-01-01

    Local field potential (LFP), the low-frequency part of the potential recorded extracellularly in the brain, reflects neural activity at the population level. The interpretation of LFP is complicated because it can mix activity from remote cells, on the order of millimeters from the electrode. To understand better the relation between the recordings and the local activity of cells we used a large-scale network thalamocortical model to compute simultaneous LFP, transmembrane currents, and spiking activity. We used this model to study the information contained in independent components obtained from the reconstructed Current Source Density (CSD), which smooths transmembrane currents, decomposed further with Independent Component Analysis (ICA). We found that the three most robust components matched well the activity of two dominating cell populations: superior pyramidal cells in layer 2/3 (rhythmic spiking) and tufted pyramids from layer 5 (intrinsically bursting). The pyramidal population from layer 2/3 could not be well described as a product of spatial profile and temporal activation, but by a sum of two such products which we recovered in two of the ICA components in our analysis, which correspond to the two first principal components of PCA decomposition of layer 2/3 population activity. At low noise one more cell population could be discerned but it is unlikely that it could be recovered in experiment given typical noise ranges. PMID:25153730

  3. Aberrant O-GlcNAcylation disrupts GNE enzyme activity in GNE myopathy.

    PubMed

    Bennmann, Dorit; Weidemann, Wenke; Thate, Annett; Kreuzmann, Denise; Horstkorte, Rüdiger

    2016-06-01

    UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is the key enzyme for the biosynthesis of sialic acids. Sialic acids are terminal monosaccharides of glycoconjugates and gangliosides, which have an essential influence on various cell interactions. The sialylation of proteins varies during development, aging, and pathogenesis of degenerative diseases such as Morbus Alzheimer, diabetes mellitus type II, or myopathies. Mutation of methionine 743 in the GNE leads to a 30% reduction of the enzyme activity and is responsible for an aggressive form of GNE myopathy. GNE myopathy or hereditary inclusion body myopathy (HIBM) is an age-dependent muscular dystrophy. Here, we analyzed the impact of the exchange of methionine to threonine at position 743 which introduces an additional potential phosphorylation/O-GlcNAcylation site. We found increased O-GlcNAcylation of the M743T variant compared to the wild-type GNE. In addition, removal of the O-GlcNAc of the M743T variant resulted in an increased activity comparable to activity of the wild-type GNE. Furthermore, the half-life of the M743T variant is two times longer than for the wild-type GNE protein. This study provides that the balance of phosphorylation and O-GlcNAcylation is decisive involved in efficiency and regulation of GNE. PMID:27037841

  4. Aberrant activation-induced cytidine deaminase expression in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia.

    PubMed

    Shi, Yang; Zhao, Xiaoxian; Durkin, Lisa; Rogers, Heesun Joyce; Hsi, Eric D

    2016-06-01

    Activation-induced cytidine deaminase (AID) is expressed in germinal center B cells and plays a critical role in somatic hypermutation and class-switch recombination of immunoglobulin genes. Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) carries a poor prognosis and is specifically treated with tyrosine kinase inhibitors. Interestingly, AID has been shown to be aberrantly expressed and functional in Ph+ ALL and is thought to contribute to genetic instability. We hypothesized that AID might be detectable in routinely processed bone marrow biopsies by immunohistochemistry (IHC) and assist in identifying Ph+ ALL. We found that AID was expressed in 26 (70%) of 37 cases of Ph+ ALL but only 1 (2.9%) of 38 cases of Ph- ALL cases. There was a significant difference in AID expression between these 2 ALL groups (P < .001, Fisher exact test). The expression of AID was confirmed by RT-PCR (reverse-transcriptase polymerase chain reaction) and correlated with IHC scoring. AID protein is expressed in a large proportion of Ph+ ALL cases at levels detectable by IHC in clinical samples and might be useful to rapidly identify cases likely to have a BCR/ABL1 fusion. PMID:26980048

  5. Changes in spontaneous neural activity immediately after an acoustic trauma: implications for neural correlates of tinnitus.

    PubMed

    Noreña, A J; Eggermont, J J

    2003-09-01

    Changes in spontaneous activity, recorded over 15-min periods before, immediately after and within hours after an acute acoustic trauma, were studied in primary auditory cortex of ketamine-anesthetized cats. We focused on the spontaneous firing rate (SFR), the peak cross-correlation coefficient (rho) and burst-firing activity. Multi-units (MUs) were grouped according to characteristic frequency (CF): MUs with a CF below the trauma-tone frequency (TF) were labeled as Be, those with a CF within 1 octave above the TF were labeled as Ab1 and those with a CF more than 1 octave above the TF were labeled as Ab2. Immediately after the trauma, the SFR was not significantly changed. The percentage of time that neurons were bursting, the mean burst duration, the number of spikes per burst and the mean inter-spike interval in a burst were enhanced. rho was locally increased in the Ab1-Ab2 and Ab2-Ab2 groups. A few hours post trauma, the SFR was increased in the Be and Ab2 groups, whereas burst-firing returned to pre-exposure levels. Moreover, rho was elevated in the Be-Ab2, Ab1-Ab2 and Ab2-Ab2 groups; this increase was significantly correlated to the changes in SFR. The results are discussed in the context of a neural correlate of tinnitus. PMID:13679145

  6. Premature lethality, hyperactivity, and aberrant phosphorylation in transgenic mice expressing a constitutively active form of Fyn

    PubMed Central

    Xia, Di; Götz, Jürgen

    2014-01-01

    The kinase Fyn, the microtubule-associated protein tau and the peptide amyloid-β (Aβ) constitute a toxic triad in Alzheimer's disease (AD). Tau's subcellular localization is mainly regulated by phosphorylation whereas Fyn's localization is dictated by palmitoylation targeting it to the plasma membrane in a reversible manner. We have previously shown that tau is required for Fyn to be targeted to the dendritic spine. We had also shown that a truncated form of tau (Δtau) that accumulates in the cell soma is capable of trapping Fyn and preventing it from entering the spine. Here we determined that palmitoylation is required for Fyn's membrane and spine localization. We further evaluated the functional consequences of neuronal over-expression of the constitutively active Y531F mutant form of Fyn (FynCA) in transgenic mice. We found that the FynCA transgenic mice displayed a reduced weight, a massively reduced lifespan and a high level of hyperactivity. The lifespan of the FynCA mice was only slightly extended by crossing them with Δtau transgenic mice, possibly reflecting differences in expression patterns of the transgenes and high levels of transgenic FynCA compared to endogenous Fyn. Analysis of synaptosomes revealed that FynCA accumulated at high levels in the spine, resulting in increased levels of the NMDA receptor subunit NR2b phosphorylated at residue Y1472. Tau was strongly phosphorylated at the AT8 epitope S202/T205 as shown by Western blot and immunohistochemistry indicating that an increased tyrosine kinase activity of Fyn has down-stream consequences for serine/threonine-directed phosphorylation. PMID:24860422

  7. Interpreting collective neural activity underlying spatial navigation in virtual reality

    NASA Astrophysics Data System (ADS)

    Meshulam, Leenoy; Gauthier, Jeff; Tank, David; Bialek, William

    2015-03-01

    Traditionally, cognitive- demanding processes like spatial navigation were studied by recording the activity of single neurons. However, recent technological progress allows imaging the simultaneous activity of large neuronal populations in awake behaving animals. This progress in experimental work calls for a similar adjustments of the modeling frameworks. To achieve a description of the ``real thermodynamics'' of the neural system, we construct maximum entropy models for optical imaging data taken in vivo, from the hippocampus of mice navigating in a virtual reality environment. This provides a natural extension of statistical mechanics applicable to brain activity, by focusing on the interactions between cells rather than on single cell's activity. We aim to determine how the topology of the energy landscape predicted by the model corresponds to the location of the animal in the environment. Since large subpopulations of the neurons in this area are spatially modulated, we expect the landscape to exhibit a large ``valley'' structure of local minima, corresponding to the animal's position along the environment. Such a finding is especially of interest because the location information emerges solely from the activity patterns that are accessible to the brain.

  8. Tcf7l1 protects the anterior neural fold from adopting the neural crest fate.

    PubMed

    Mašek, Jan; Machoň, Ondřej; Kořínek, Vladimír; Taketo, M Mark; Kozmik, Zbyněk

    2016-06-15

    The neural crest (NC) is crucial for the evolutionary diversification of vertebrates. NC cells are induced at the neural plate border by the coordinated action of several signaling pathways, including Wnt/β-catenin. NC cells are normally generated in the posterior neural plate border, whereas the anterior neural fold is devoid of NC cells. Using the mouse model, we show here that active repression of Wnt/β-catenin signaling is required for maintenance of neuroepithelial identity in the anterior neural fold and for inhibition of NC induction. Conditional inactivation of Tcf7l1, a transcriptional repressor of Wnt target genes, leads to aberrant activation of Wnt/β-catenin signaling in the anterior neuroectoderm and its conversion into NC. This reduces the developing prosencephalon without affecting the anterior-posterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/β-catenin signaling gradient. PMID:27302397

  9. Activation of endogenous neural stem cells for multiple sclerosis therapy.

    PubMed

    Michailidou, Iliana; de Vries, Helga E; Hol, Elly M; van Strien, Miriam E

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  10. Natural lecithin promotes neural network complexity and activity.

    PubMed

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-01-01

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called "essential" fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications. PMID:27228907

  11. Natural lecithin promotes neural network complexity and activity

    PubMed Central

    Latifi, Shahrzad; Tamayol, Ali; Habibey, Rouhollah; Sabzevari, Reza; Kahn, Cyril; Geny, David; Eftekharpour, Eftekhar; Annabi, Nasim; Blau, Axel; Linder, Michel; Arab-Tehrany, Elmira

    2016-01-01

    Phospholipids in the brain cell membranes contain different polyunsaturated fatty acids (PUFAs), which are critical to nervous system function and structure. In particular, brain function critically depends on the uptake of the so-called “essential” fatty acids such as omega-3 (n-3) and omega-6 (n-6) PUFAs that cannot be readily synthesized by the human body. We extracted natural lecithin rich in various PUFAs from a marine source and transformed it into nanoliposomes. These nanoliposomes increased neurite outgrowth, network complexity and neural activity of cortical rat neurons in vitro. We also observed an upregulation of synapsin I (SYN1), which supports the positive role of lecithin in synaptogenesis, synaptic development and maturation. These findings suggest that lecithin nanoliposomes enhance neuronal development, which may have an impact on devising new lecithin delivery strategies for therapeutic applications. PMID:27228907

  12. Activation of endogenous neural stem cells for multiple sclerosis therapy

    PubMed Central

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability. A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs). Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions. PMID:25653584

  13. Effects of Near-Infrared Laser on Neural Cell Activity

    NASA Astrophysics Data System (ADS)

    Mochizuki-Oda, Noriko; Kataoka, Yosky; Yamada, Hisao; Awazu, Kunio

    2004-08-01

    Near-infrared laser has been used to relieve patients from various kinds of pain caused by postherpetic neuralgesia, myofascial dysfunction, surgical and traumatic wound, cancer, and rheumatoid arthritis. Clinically, He-Ne (λ=632.8 nm, 780 nm) and Ga-Al-As (805 ± 25 nm) lasers are used to irradiate trigger points or nerve ganglion. However the precise mechanisms of such biological actions of the laser have not yet been resolved. Since laser therapy is often effective to suppress the pain caused by hyperactive excitation of sensory neurons, interactions with laser light and neural cells are suggested. As neural excitation requires large amount of energy liberated from adenosine triphosphate (ATP), we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat central nervous system and isolated mitochondria from brain. The diode laser was applied for 15 min with irradiance of 4.8 W/cm2 on a 2 mm-diameter spot at the brain surface. Tissue ATP content of the irradiated area in the cerebral cortex was 19 % higher than that of the non-treated area (opposite side of the cortex), whereas the ADP content showed no significant difference. Irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the brain tissue was increased 4.5 - 5.0 °C during the irradiation of both 830-nm and 652-nm laser light. Direct irradiation of the mitochondrial suspension did not show any wavelength-dependent acceleration of respiration rate nor ATP synthesis. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from specific effect of the laser operated at 830 nm. Electrophysiological studies showed the hyperpolarization of membrane potential of isolated neurons and decrease in membrane resistance with irradiation of the laser, suggesting an activation of potassium channels. Intracellular ATP is reported to regulate some kinds of potassium channels. Possible mechanisms

  14. Can simple interactions capture complex features of neural activity underlying behavior in a virtual reality environment?

    NASA Astrophysics Data System (ADS)

    Meshulam, Leenoy; Gauthier, Jeffrey; Brody, Carlos; Tank, David; Bialek, William

    The complex neural interactions which are abundant in most recordings of neural activity are relatively poorly understood. A prime example of such interactions can be found in the in vivo neural activity which underlies complex behaviors of mice, imaged in brain regions such as hippocampus and parietal cortex. Experimental techniques now allow us to accurately follow these neural interactions in the simultaneous activity of large neuronal populations of awake behaving animals. Here, we demonstrate that pairwise maximum entropy models can predict a surprising number of properties of the neural activity. The models, that are constrained with activity rates and interactions between pairs of neurons, are well fit to the activity `states' in the hippocampus and cortex of mice performing cognitive tasks while navigating in a virtual reality environment.

  15. Aberrant Activation of the RANK Signaling Receptor Induces Murine Salivary Gland Tumors

    PubMed Central

    Jacob, Allison P.; Dougall, William C.; Ittmann, Michael M.; Lydon, John P.

    2015-01-01

    Unlike cancers of related exocrine tissues such as the mammary and prostate gland, diagnosis and treatment of aggressive salivary gland malignancies have not markedly advanced in decades. Effective clinical management of malignant salivary gland cancers is undercut by our limited knowledge concerning the key molecular signals that underpin the etiopathogenesis of this rare and heterogeneous head and neck cancer. Without knowledge of the critical signals that drive salivary gland tumorigenesis, tumor vulnerabilities cannot be exploited that allow for targeted molecular therapies. This knowledge insufficiency is further exacerbated by a paucity of preclinical mouse models (as compared to other cancer fields) with which to both study salivary gland pathobiology and test novel intervention strategies. Using a mouse transgenic approach, we demonstrate that deregulation of the Receptor Activator of NFkB Ligand (RANKL)/RANK signaling axis results in rapid tumor development in all three major salivary glands. In line with its established role in other exocrine gland cancers (i.e., breast cancer), the RANKL/RANK signaling axis elicits an aggressive salivary gland tumor phenotype both at the histologic and molecular level. Despite the ability of this cytokine signaling axis to drive advanced stage disease within a short latency period, early blockade of RANKL/RANK signaling markedly attenuates the development of malignant salivary gland neoplasms. Together, our findings have uncovered a tumorigenic role for RANKL/RANK in the salivary gland and suggest that targeting this pathway may represent a novel therapeutic intervention approach in the prevention and/or treatment of this understudied head and neck cancer. PMID:26061636

  16. Decorrelation of Neural-Network Activity by Inhibitory Feedback

    PubMed Central

    Einevoll, Gaute T.; Diesmann, Markus

    2012-01-01

    Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between

  17. Evidence-Based Systematic Review: Effects of Neuromuscular Electrical Stimulation on Swallowing and Neural Activation

    ERIC Educational Resources Information Center

    Clark, Heather; Lazarus, Cathy; Arvedson, Joan; Schooling, Tracy; Frymark, Tobi

    2009-01-01

    Purpose: To systematically review the literature examining the effects of neuromuscular electrical stimulation (NMES) on swallowing and neural activation. The review was conducted as part of a series examining the effects of oral motor exercises (OMEs) on speech, swallowing, and neural activation. Method: A systematic search was conducted to…

  18. Volitional control of neural activity: implications for brain–computer interfaces

    PubMed Central

    Fetz, Eberhard E

    2007-01-01

    Successful operation of brain–computer interfaces (BCI) and brain–machine interfaces (BMI) depends significantly on the degree to which neural activity can be volitionally controlled. This paper reviews evidence for such volitional control in a variety of neural signals, with particular emphasis on the activity of cortical neurons. Some evidence comes from conventional experiments that reveal volitional modulation in neural activity related to behaviours, including real and imagined movements, cognitive imagery and shifts of attention. More direct evidence comes from studies on operant conditioning of neural activity using biofeedback, and from BCI/BMI studies in which neural activity controls cursors or peripheral devices. Limits in the degree of accuracy of control in the latter studies can be attributed to several possible factors. Some of these factors, particularly limited practice time, can be addressed with long-term implanted BCIs. Preliminary observations with implanted circuits implementing recurrent BCIs are summarized. PMID:17234689

  19. Integration of active devices on smart polymers for neural interfaces

    NASA Astrophysics Data System (ADS)

    Avendano-Bolivar, Adrian Emmanuel

    The increasing ability to ever more precisely identify and measure neural interactions and other phenomena in the central and peripheral nervous systems is revolutionizing our understanding of the human body and brain. To facilitate further understanding, more sophisticated neural devices, perhaps using microelectronics processing, must be fabricated. Materials often used in these neural interfaces, while compatible with these fabrication processes, are not optimized for long-term use in the body and are often orders of magnitude stiffer than the tissue with which they interact. Using the smart polymer substrates described in this work, suitability for processing as well as chronic implantation is demonstrated. We explore how to integrate reliable circuitry onto these flexible, biocompatible substrates that can withstand the aggressive environment of the body. To increase the capabilities of these devices beyond individual channel sensing and stimulation, active electronics must also be included onto our systems. In order to add this functionality to these substrates and explore the limits of these devices, we developed a process to fabricate single organic thin film transistors with mobilities up to 0.4 cm2/Vs and threshold voltages close to 0V. A process for fabricating organic light emitting diodes on flexible substrates is also addressed. We have set a foundation and demonstrated initial feasibility for integrating multiple transistors onto thin-film flexible devices to create new applications, such as matrix addressable functionalized electrodes and organic light emitting diodes. A brief description on how to integrate waveguides for their use in optogenetics is addressed. We have built understanding about device constraints on mechanical, electrical and in vivo reliability and how various conditions affect the electronics' lifetime. We use a bi-layer gate dielectric using an inorganic material such as HfO 2 combined with organic Parylene-c. A study of

  20. Chromosome aberrations in peripheral lymphocytes and radiation dose to active bone marrow in patients treated for cancer of the cervix

    SciTech Connect

    Kleinerman, R.A.; Littlefield, L.G.; Tarone, R.E.; Machado, S.G.; Blettner, M.; Peters, L.J.; Boice, J.D. Jr. )

    1989-07-01

    An international study of cervical cancer patients reported a doubling of the risk for leukemia following radiotherapy. To evaluate the extent of residual chromosome damage in circulating T-cell lymphocytes in this population, approximately 200 metaphases were examined from each of 96 irradiated and 26 nonirradiated cervical cancer patients treated more than 17 years ago (average 23 years). Radiation dose averaged over the total red bone marrow was estimated to be 8.1 Gy. The type and frequency of stable and unstable chromosome aberrations were quantified in 24,117 metaphases. Unstable aberrations did not differ significantly between irradiated and nonirradiated patients (P greater than 0.5). Stable aberrations (i.e., translocations, inversions, or chromosomes with deleted segments), however, were significantly higher among irradiated (2.8 per 100 cells) compared to nonirradiated (0.7 per 100 cells) women (P less than 10(4)). The frequency of these stable aberrations was found to increase significantly with increasing dose to the bone marrow. These data indicate that a direct relationship between radiation dose and extent of damage to somatic cells persists in populations and can be detected many years after partial-body radiation exposure. The stable aberration rate in irradiated cervical cancer patients was 50 to 75% lower than those observed 25 years or more after radiation exposure in atomic bomb survivors and in ankylosing spondylitis patients treated with radiotherapy. The average marrow dose was only 1 Gy in the examined atomic bomb survivors and 3.5 Gy in the ankylosing spondylitis patients. It appears, then, that a very high dose delivered to the pelvic cavity in fractionated doses resulted in far fewer persistent stable aberrations than lower doses delivered either in acute whole-body exposure or in fractionated doses to the spinal column and sacroiliac joints.

  1. Neural activity associated with distinguishing concurrent auditory objects

    NASA Astrophysics Data System (ADS)

    Alain, Claude; Schuler, Benjamin M.; McDonald, Kelly L.

    2002-02-01

    The neural processes underlying concurrent sound segregation were examined by using event-related brain potentials. Participants were presented with complex sounds comprised of multiple harmonics, one of which could be mistuned so that it was no longer an integer multiple of the fundamental. In separate blocks of trials, short-, middle-, and long-duration sounds were presented and participants indicated whether they heard one sound (i.e., buzz) or two sounds (i.e., buzz plus another sound with a pure-tone quality). The auditory stimuli were also presented while participants watched a silent movie in order to evaluate the extent to which the mistuned harmonic could be automatically detected. The perception of the mistuned harmonic as a separate sound was associated with a biphasic negative-positive potential that peaked at about 150 and 350 ms after sound onset, respectively. Long duration sounds also elicited a sustained potential that was greater in amplitude when the mistuned harmonic was perceptually segregated from the complex sound. The early negative wave, referred to as the object-related negativity (ORN), was present during both active and passive listening, whereas the positive wave and the mistuning-related changes in sustained potentials were present only when participants attended to the stimuli. These results are consistent with a two-stage model of auditory scene analysis in which the acoustic wave is automatically decomposed into perceptual groups that can be identified by higher executive functions. The ORN and the positive waves were little affected by sound duration, indicating that concurrent sound segregation depends on transient neural responses elicited by the discrepancy between the mistuned harmonic and the harmonic frequency expected based on the fundamental frequency of the incoming stimulus.

  2. Can Neural Activity Propagate by Endogenous Electrical Field?

    PubMed

    Qiu, Chen; Shivacharan, Rajat S; Zhang, Mingming; Durand, Dominique M

    2015-12-01

    It is widely accepted that synaptic transmissions and gap junctions are the major governing mechanisms for signal traveling in the neural system. Yet, a group of neural waves, either physiological or pathological, share the same speed of ∼0.1 m/s without synaptic transmission or gap junctions, and this speed is not consistent with axonal conduction or ionic diffusion. The only explanation left is an electrical field effect. We tested the hypothesis that endogenous electric fields are sufficient to explain the propagation with in silico and in vitro experiments. Simulation results show that field effects alone can indeed mediate propagation across layers of neurons with speeds of 0.12 ± 0.09 m/s with pathological kinetics, and 0.11 ± 0.03 m/s with physiologic kinetics, both generating weak field amplitudes of ∼2-6 mV/mm. Further, the model predicted that propagation speed values are inversely proportional to the cell-to-cell distances, but do not significantly change with extracellular resistivity, membrane capacitance, or membrane resistance. In vitro recordings in mice hippocampi produced similar speeds (0.10 ± 0.03 m/s) and field amplitudes (2.5-5 mV/mm), and by applying a blocking field, the propagation speed was greatly reduced. Finally, osmolarity experiments confirmed the model's prediction that cell-to-cell distance inversely affects propagation speed. Together, these results show that despite their weak amplitude, electric fields can be solely responsible for spike propagation at ∼0.1 m/s. This phenomenon could be important to explain the slow propagation of epileptic activity and other normal propagations at similar speeds. PMID:26631463

  3. Activity-Dependent Modulation of Neural Circuit Synaptic Connectivity

    PubMed Central

    Tessier, Charles R.; Broadie, Kendal

    2009-01-01

    In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; (1) early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and (2) subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circuits are “hard-wired” in a purely activity-independent manner. This conclusion has been challenged recently through the use of new transgenic tools employed in the powerful Drosophila system, which have allowed unprecedented temporal control and single neuron imaging resolution. These recent studies reveal that activity-dependent mechanisms are indeed required to refine circuit maps in Drosophila during precise, restricted windows of late-phase development. Such mechanisms of circuit refinement may be key to understanding a number of human neurological diseases, including developmental disorders such as Fragile X syndrome (FXS) and autism, which are hypothesized to result from defects in synaptic connectivity and activity-dependent circuit function. This review focuses on our current understanding of activity-dependent synaptic connectivity in Drosophila, primarily through analyzing the role of the fragile X mental retardation protein (FMRP) in the Drosophila FXS disease model. The particular emphasis of this review is on the expanding array of new genetically-encoded tools that are allowing cellular events and molecular players to be dissected with ever greater precision and detail. PMID:19668708

  4. Preferential hydrolysis of aberrant intermediates by the type II thioesterase in Escherichia coli nonribosomal enterobactin synthesis: substrate specificities and mutagenic studies on the active-site residues.

    PubMed

    Guo, Zu-Feng; Sun, Yueru; Zheng, Suilan; Guo, Zhihong

    2009-03-01

    The type II thioesterase EntH is a hotdog fold protein required for optimal nonribosomal biosynthesis of enterobactin in Escherichia coli. Its proposed proofreading activity in the biosynthesis is confirmed by its efficient restoration of enterobactin synthesis blocked in vitro by analogs of the cognate precursor 2,3-dihydroxybenzoate. Steady-state kinetic studies show that EntH recognizes the phosphopantetheine group and the pattern of hydroxylation in the aryl moiety of its thioester substrates. Remarkably, it is able to distinguish aberrant intermediates from the normal one in the enterobactin assembly line by demonstrating at least 10-fold higher catalytic efficiency toward thioesters derived from aberrant aryl precursors without a para-hydroxyl group, such as salicylate. By structural comparison and site-directed mutagenesis, the thioesterase is found to possess an active site closely resembling that of the 4-hydroxybenzoyl-CoA thioesterase from Arthrobacter sp. strain SU and to involve an acidic residue (glutamate-63) as the catalytic base or nucleophile like all other hotdog thioesterases. In addition, the EntH specificities toward the substrate hydroxylation pattern are found to depend on the active-site histidine-54, threonine-64, serine-67, and methionine-68 with the selectivity significantly reduced or even reversed when they are individually replaced by alanine. These residues are likely responsible for differential interaction of the enzyme with the substrates which leads to distinction between the normal and aberrant precursors in the enterobactin assembly line. These results show that the type II thioesterase evolves its distinctive ability to recognize the aberrant intermediates from the versatile catalytic platform of hotdog proteins and suggests an active search mechanism for type II thioesterases in nonribosomal peptide synthesis. PMID:19193103

  5. Light-Activated Ion Channels for Remote Control of Neural Activity

    PubMed Central

    Chambers, James J.; Kramer, Richard H.

    2009-01-01

    Light-activated ion channels provide a new opportunity to precisely and remotely control neuronal activity for experimental applications in neurobiology. In the past few years, several strategies have arisen that allow light to control ion channels and therefore neuronal function. Light-based triggers for ion channel control include caged compounds, which release active neurotransmitters when photolyzed with light, and natural photoreceptive proteins, which can be expressed exogenously in neurons. More recently, a third type of light trigger has been introduced: a photoisomerizable tethered ligand that directly controls ion channel activity in a light-dependent manner. Beyond the experimental applications for light-gated ion channels, there may be clinical applications in which these light-sensitive ion channels could prove advantageous over traditional methods. Electrodes for neural stimulation to control disease symptoms are invasive and often difficult to reposition between cells in tissue. Stimulation by chemical agents is difficult to constrain to individual cells and has limited temporal accuracy in tissue due to diffusional limitations. In contrast, ion channels that can be directly activated with light allow control with unparalleled spatial and temporal precision. The goal of this chapter is to describe light-regulated ion channels and how they have been tailored to control different aspects of neural activity, and how to use these channels to manipulate and better understand development, function, and plasticity of neurons and neural circuits. PMID:19195553

  6. Sensitive red protein calcium indicators for imaging neural activity

    PubMed Central

    Dana, Hod; Mohar, Boaz; Sun, Yi; Narayan, Sujatha; Gordus, Andrew; Hasseman, Jeremy P; Tsegaye, Getahun; Holt, Graham T; Hu, Amy; Walpita, Deepika; Patel, Ronak; Macklin, John J; Bargmann, Cornelia I; Ahrens, Misha B; Schreiter, Eric R; Jayaraman, Vivek; Looger, Loren L; Svoboda, Karel; Kim, Douglas S

    2016-01-01

    Genetically encoded calcium indicators (GECIs) allow measurement of activity in large populations of neurons and in small neuronal compartments, over times of milliseconds to months. Although GFP-based GECIs are widely used for in vivo neurophysiology, GECIs with red-shifted excitation and emission spectra have advantages for in vivo imaging because of reduced scattering and absorption in tissue, and a consequent reduction in phototoxicity. However, current red GECIs are inferior to the state-of-the-art GFP-based GCaMP6 indicators for detecting and quantifying neural activity. Here we present improved red GECIs based on mRuby (jRCaMP1a, b) and mApple (jRGECO1a), with sensitivity comparable to GCaMP6. We characterized the performance of the new red GECIs in cultured neurons and in mouse, Drosophila, zebrafish and C. elegans in vivo. Red GECIs facilitate deep-tissue imaging, dual-color imaging together with GFP-based reporters, and the use of optogenetics in combination with calcium imaging. DOI: http://dx.doi.org/10.7554/eLife.12727.001 PMID:27011354

  7. Emotion disrupts neural activity during selective attention in psychopathy.

    PubMed

    Sadeh, Naomi; Spielberg, Jeffrey M; Heller, Wendy; Herrington, John D; Engels, Anna S; Warren, Stacie L; Crocker, Laura D; Sutton, Bradley P; Miller, Gregory A

    2013-03-01

    Dimensions of psychopathy are theorized to be associated with distinct cognitive and emotional abnormalities that may represent unique neurobiological risk factors for the disorder. This hypothesis was investigated by examining whether the psychopathic personality dimensions of fearless-dominance and impulsive-antisociality moderated neural activity and behavioral responses associated with selective attention and emotional processing during an emotion-word Stroop task in 49 adults. As predicted, the dimensions evidenced divergent selective-attention deficits and sensitivity to emotional distraction. Fearless-dominance was associated with disrupted attentional control to positive words, and activation in right superior frontal gyrus mediated the relationship between fearless-dominance and errors to positive words. In contrast, impulsive-antisociality evidenced increased behavioral interference to both positive and negative words and correlated positively with recruitment of regions associated with motivational salience (amygdala, orbitofrontal cortex, insula), emotion regulation (temporal cortex, superior frontal gyrus) and attentional control (dorsal anterior cingulate cortex). Individuals high on both dimensions had increased recruitment of regions related to attentional control (temporal cortex, rostral anterior cingulate cortex), response preparation (pre-/post-central gyri) and motivational value (orbitofrontal cortex) in response to negative words. These findings provide evidence that the psychopathy dimensions represent dual sets of risk factors characterized by divergent dysfunction in cognitive and affective processes. PMID:22210673

  8. Sensitive red protein calcium indicators for imaging neural activity.

    PubMed

    Dana, Hod; Mohar, Boaz; Sun, Yi; Narayan, Sujatha; Gordus, Andrew; Hasseman, Jeremy P; Tsegaye, Getahun; Holt, Graham T; Hu, Amy; Walpita, Deepika; Patel, Ronak; Macklin, John J; Bargmann, Cornelia I; Ahrens, Misha B; Schreiter, Eric R; Jayaraman, Vivek; Looger, Loren L; Svoboda, Karel; Kim, Douglas S

    2016-01-01

    Genetically encoded calcium indicators (GECIs) allow measurement of activity in large populations of neurons and in small neuronal compartments, over times of milliseconds to months. Although GFP-based GECIs are widely used for in vivo neurophysiology, GECIs with red-shifted excitation and emission spectra have advantages for in vivo imaging because of reduced scattering and absorption in tissue, and a consequent reduction in phototoxicity. However, current red GECIs are inferior to the state-of-the-art GFP-based GCaMP6 indicators for detecting and quantifying neural activity. Here we present improved red GECIs based on mRuby (jRCaMP1a, b) and mApple (jRGECO1a), with sensitivity comparable to GCaMP6. We characterized the performance of the new red GECIs in cultured neurons and in mouse, Drosophila, zebrafish and C. elegans in vivo. Red GECIs facilitate deep-tissue imaging, dual-color imaging together with GFP-based reporters, and the use of optogenetics in combination with calcium imaging. PMID:27011354

  9. Compassionate attitude towards others' suffering activates the mesolimbic neural system.

    PubMed

    Kim, Ji-Woong; Kim, Sung-Eun; Kim, Jae-Jin; Jeong, Bumseok; Park, Chang-Hyun; Son, Ae Ree; Song, Ji Eun; Ki, Seon Wan

    2009-08-01

    Compassion is one of the essential components which enable individuals to enter into and maintain relationships of caring. Compassion tends to motivate us to help people who are emotionally suffering. It is also known that a feeling of intrinsic reward may occur as a result of experiencing compassion for others. We conducted this study to understand the neural nature of compassion for other people's emotional state. Twenty-one healthy normal volunteers participated in this study. We used a 2 x 2 factorial design in which each subject was asked to assume a compassionate attitude or passive attitude while viewing the sad or neutral facial affective pictures during functional magnetic imaging. The main effect of a compassionate attitude was observed in the medial frontal cortex, the subgenual frontal cortex, the inferior frontal cortex and the midbrain regions. A test of the interaction between a compassionate attitude and sad facial affect revealed significant activations in the midbrain-ventral striatum/septal network region. The results of this study suggest that taking a compassionate attitude towards other people's sad expressions modulate the activities of the midbrain-ventral striatum/septal region network, which is known to play a role in the prosocial/social approach motivation and its accompanied rewarding feeling. PMID:19428038

  10. Patterns of Neural Activity in Networks with Complex Connectivity

    NASA Astrophysics Data System (ADS)

    Solla, Sara A.

    2008-03-01

    An understanding of emergent dynamics on complex networks requires investigating the interplay between the intrinsic dynamics of the node elements and the connectivity of the network in which they are embedded. In order to address some of these questions in a specific scenario of relevance to the dynamical states of neural ensembles, we have studied the collective behavior of excitable model neurons in a network with small-world topology. The small-world network has local lattice order, but includes a number of randomly placed connections that may provide connectivity shortcuts. This topology bears a schematic resemblance to the connectivity of the cerebral cortex, in which neurons are most strongly coupled to nearby cells within fifty to a hundred micrometers, but also make projections to cells millimeters away. We find that the dynamics of this small-world network of excitable neurons depend mostly on both the density of shortcuts and the delay associated with neuronal projections. In the regime of low shortcut density, the system exhibits persistent activity in the form of propagating waves, which annihilate upon collision and are spawned anew via the re-injection of activity through shortcut connections. As the density of shortcuts reaches a critical value, the system undergoes a transition to failure. The critical shortcut density results from matching the time associated with a recurrent path through the network to an intrinsic recovery time of the individual neurons. Furthermore, if the delay associated with neuronal interactions is sufficiently long, activity reemerges above the critical density of shortcuts. The activity in this regime exhibits long, chaotic transients composed of noisy, large-amplitude population bursts.

  11. TLR2 Activation Inhibits Embryonic Neural Progenitor Cell Proliferation

    PubMed Central

    Okun, Eitan; Griffioen, Kathleen J.; Gen-Son, Tae; Lee, Jong-Hwan; Roberts, Nicholas J.; Mughal, Mohamed R.; Hutchison, Emmette; Cheng, Aiwu; Arumugam, Thiruma V.; Lathia, Justin D.; van Praag, Henriette; Mattson, Mark P.

    2010-01-01

    Toll-like receptors (TLRs) play essential roles in innate immunity, and increasing evidence indicates that these receptors are expressed in neurons, astrocytes and microglia in the brain, where they mediate responses to infection, stress and injury. To address the possibility that TLR2 heterodimer activation could affect progenitor cells in the developing brain, we analyzed the expression of TLR2 throughout the mouse cortical development, and assessed the role of TLR2 heterodimer activation in neural progenitor cell (NPC) proliferation. TLR2 mRNA and protein was expressed in the cortex in embryonic and early postnatal stages of development, and in cultured cortical NPC. While NPC from TLR2-deficient and wild type embryos had the same proliferative capacity, TLR2 activation by the synthetic bacterial lipopeptides Pam3CSK4 and FSL1, or low molecular weight hyaluronan, an endogenous ligand for TLR2, inhibited neurosphere formation in vitro. Intracerebral in utero administration of TLR2 ligands resulted in ventricular dysgenesis characterized by increased ventricle size, reduced proliferative area around the ventricles, increased cell density, an increase in PH3+ cells and a decrease in BrdU+ cells in the sub-ventricular zone. Our findings indicate that loss of TLR2 does not result in defects in cerebral development. However, TLR2 is expressed and functional in the developing telencephalon from early embryonic stages and infectious agent-related activation of TLR2 inhibits NPC proliferation. TLR2–mediated inhibition of NPC proliferation may therefore be a mechanism by which infection, ischemia and inflammation adversely affect brain development. PMID:20456021

  12. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation

    PubMed Central

    Sameiro-Barbosa, Catia M.; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID:27559306

  13. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation.

    PubMed

    Sameiro-Barbosa, Catia M; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID:27559306

  14. Vinca alkaloids cause aberrant ROS-mediated JNK activation, Mcl-1 downregulation, DNA damage, mitochondrial dysfunction, and apoptosis in lung adenocarcinoma cells.

    PubMed

    Chiu, Wei-Hsin; Luo, Sheng-Jei; Chen, Chia-Ling; Cheng, Jai-Hong; Hsieh, Chia-Yuan; Wang, Chi-Yun; Huang, Wei-Ching; Su, Wu-Chou; Lin, Chiou-Feng

    2012-05-01

    Vinca alkaloids are clinically used to inhibit the growth of malignancy by interfering with microtubule polymerization. The purpose of this study was to identify the molecular mechanisms underlying growth inhibition as well as apoptosis in vinca alkaloid-treated lung adenocarcinoma cells. Consistent with nocodazole, treatment with vinorelbine (VNR) caused mitotic prometaphase arrest in a time-dependent manner, accompanied by cell apoptosis, dependent on both dose and time. VNR sequentially induced mitochondrial transmembrane potential (MTP) loss and caspase-dependent apoptosis following myeloid cell leukemia (Mcl) 1 downregulation. Prolonged activation of c-Jun N-terminal kinase (JNK) was required for vinca alkaloid- and nocodazole-induced apoptosis but not cell cycle arrest. Vinca alkaloids and nocodazole caused glutathione/reactive oxygen species (ROS) imbalance, and inhibiting ROS prevented prolonged JNK activation, decreased Mcl-1 levels, MTP loss, and apoptosis. Notably, cell size and granularity were enlarged in stimulated cells; unexpectedly, many ROS-producing mitochondria were accumulated followed by aberrant JNK-mediated mitochondrial dysfunction. Unlike cisplatin, which causes DNA damage in each phase of the cell cycle, VNR and nocodazole induced aberrant JNK-regulated DNA damage in prometaphase; however, inhibiting ATM (ataxia telangiectasia, mutated) and ATR (ATM and Rad3-related) did not reverse mitotic arrest or apoptosis. These results demonstrate an essential role of ROS in vinca alkaloid-induced aberrant JNK-mediated Mcl-1 downregulation and DNA damage followed by mitochondrial dysfunction-related apoptosis but not mitotic arrest. PMID:22285910

  15. Aberrant amino acid signaling promotes growth and metastasis of hepatocellular carcinomas through Rab1A-dependent activation of mTORC1 by Rab1A

    PubMed Central

    Yang, Yang; Zhang, Mei-Yin; Rao, Hui-Lan; Wang, Hui-Yun; Zheng, X.F. Steven

    2015-01-01

    mTORC1 is a master regulator of cell growth and proliferation, and an established anticancer drug target. Aberrant mTORC1 signaling is common in hepatocellular carcinoma (HCC), but the underlying mechanism remains elusive. Rab1A is a newly identified mTORC1 activator that mediates an alternative amino acid (AA) signaling branch to Rag GTPases. Because liver is a physiological hub for nutrient sensing and metabolic homeostasis, we investigated the possible role of Rab1A in HCC. We found that Rab1A is frequently overexpressed in HCC, which enhances hyperactive AA-mTORC1 signaling, promoting malignant growth and metastasis of HCC in vitro and in vivo. Moreover, aberrant Rab1A expression is closely associated with poor prognosis. Strikingly, aberrant Rab1A overexpression leads to increased rapamycin sensitivity, indicating that inappropriate activation of AA signaling is a cancer-driving event in HCC. Our findings further suggest that Rab1A is a valuable biomarker for prognosis and personalized mTORC1-targeted therapy in liver cancer. PMID:26308575

  16. Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis

    PubMed Central

    Shih, Tsung-Chieh; Hsieh, Sen-Yung; Hsieh, Yi-Yueh; Chen, Tse-Chin; Yeh, Chien-Yu; Lin, Chun-Jung; Lin, Deng-Yn; Chiu, Cheng-Tang

    2008-01-01

    AIM: To investigate the role of nuclear factor of activated T cell 2 (NFAT2), the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis (UC). METHODS: We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn’s disease (CD), non-specific colitis, and 5 healthy individuals, respectively. RESULTS: Up-regulation with profound nucleo-translocation/activation of NFAT2 of lamina propria mononuclear cells (LPMC) of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC, as compared to CD or NC (P < 0.001, Kruskal-Wallis test). Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T, but was less prominent in CD4+ T cells or CD20+B cells. It was strongly associated with the disease activity, including endoscopic stage (τ = 0.2145, P = 0.0281) and histologic grade (τ = 0.4167, P < 0.001). CONCLUSION: We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis. PMID:18350607

  17. Neural activation in arousal and reward areas of the brain in day-active and night-active grass rats.

    PubMed

    Castillo-Ruiz, A; Nixon, J P; Smale, L; Nunez, A A

    2010-01-20

    In the diurnal unstriped Nile grass rat (Arvicanthis niloticus) access to a running wheel can trigger a shift in active phase preference, with some individuals becoming night-active (NA), while others continue to be day-active (DA). To investigate the contributions of different neural systems to the support of this shift in locomotor activity, we investigated the association between chronotype and Fos expression during the day and night in three major nuclei in the basal forebrain (BF) cholinergic (ACh) arousal system - medial septum (MS), vertical and horizontal diagonal band of Broca (VDB and HDB respectively) -, and whether neural activation in these areas was related to neural activity in the orexinergic system. We also measured Fos expression in dopaminergic and non-dopaminergic cells of two components of the reward system that also participate in arousal - the ventral tegmental area (VTA) and supramammillary nucleus (SUM). NAs and DAs were compared to animals with no wheels. NAs had elevated Fos expression at night in ACh cells, but only in the HDB. In the non-cholinergic cells of the BF of NAs, enhanced nocturnal Fos expression was almost universally seen, but only associated with activation of the orexinergic system for the MS/VDB region. For some of the areas and cell types of the BF, the patterns of Fos expression of DAs appeared similar to those of NAs, but were never associated with activation of the orexinergic system. Also common to DAs and NAs was a general increase in Fos expression in non-dopaminergic cells of the SUM and anterior VTA. Thus, in this diurnal species, voluntary exercise and a shift to a nocturnal chronotype changes neural activity in arousal and reward areas of the brain known to regulate a broad range of neural functions and behaviors, which may be also affected in human shift workers. PMID:19837140

  18. SNW1 is a critical regulator of spatial BMP activity, neural plate border formation, and neural crest specification in vertebrate embryos.

    PubMed

    Wu, Mary Y; Ramel, Marie-Christine; Howell, Michael; Hill, Caroline S

    2011-01-01

    Bone morphogenetic protein (BMP) gradients provide positional information to direct cell fate specification, such as patterning of the vertebrate ectoderm into neural, neural crest, and epidermal tissues, with precise borders segregating these domains. However, little is known about how BMP activity is regulated spatially and temporally during vertebrate development to contribute to embryonic patterning, and more specifically to neural crest formation. Through a large-scale in vivo functional screen in Xenopus for neural crest fate, we identified an essential regulator of BMP activity, SNW1. SNW1 is a nuclear protein known to regulate gene expression. Using antisense morpholinos to deplete SNW1 protein in both Xenopus and zebrafish embryos, we demonstrate that dorsally expressed SNW1 is required for neural crest specification, and this is independent of mesoderm formation and gastrulation morphogenetic movements. By exploiting a combination of immunostaining for phosphorylated Smad1 in Xenopus embryos and a BMP-dependent reporter transgenic zebrafish line, we show that SNW1 regulates a specific domain of BMP activity in the dorsal ectoderm at the neural plate border at post-gastrula stages. We use double in situ hybridizations and immunofluorescence to show how this domain of BMP activity is spatially positioned relative to the neural crest domain and that of SNW1 expression. Further in vivo and in vitro assays using cell culture and tissue explants allow us to conclude that SNW1 acts upstream of the BMP receptors. Finally, we show that the requirement of SNW1 for neural crest specification is through its ability to regulate BMP activity, as we demonstrate that targeted overexpression of BMP to the neural plate border is sufficient to restore neural crest formation in Xenopus SNW1 morphants. We conclude that through its ability to regulate a specific domain of BMP activity in the vertebrate embryo, SNW1 is a critical regulator of neural plate border formation and

  19. Neural activity during interoceptive awareness and its associations with alexithymia—An fMRI study in major depressive disorder and non-psychiatric controls

    PubMed Central

    Wiebking, Christine; Northoff, Georg

    2015-01-01

    Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in

  20. Phyllanthus emblica Fruit Extract Activates Spindle Assembly Checkpoint, Prevents Mitotic Aberrations and Genomic Instability in Human Colon Epithelial NCM460 Cells.

    PubMed

    Guo, Xihan; Wang, Xu

    2016-01-01

    The fruit of Phyllanthus emblica Linn. (PE) has been widely consumed as a functional food and folk medicine in Southeast Asia due to its remarkable nutritional and pharmacological effects. Previous research showed PE delays mitotic progress and increases genomic instability (GIN) in human colorectal cancer cells. This study aimed to investigate the similar effects of PE by the biomarkers related to spindle assembly checkpoint (SAC), mitotic aberrations and GIN in human NCM460 normal colon epithelial cells. Cells were treated with PE and harvested differently according to the biomarkers observed. Frequencies of micronuclei (MN), nucleoplasmic bridge (NPB) and nuclear bud (NB) in cytokinesis-block micronucleus assay were used as indicators of GIN. Mitotic aberrations were assessed by the biomarkers of chromosome misalignment, multipolar division, chromosome lagging and chromatin bridge. SAC activity was determined by anaphase-to- metaphase ratio (AMR) and the expression of core SAC gene budding uninhibited by benzimidazoles related 1 (BubR1). Compared with the control, PE-treated cells showed (1) decreased incidences of MN, NPB and NB (p < 0.01); (2) decreased frequencies of all mitotic aberration biomarkers (p < 0.01); and (3) decreased AMR (p < 0.01) and increased BubR1 expression (p < 0.001). The results revealed PE has the potential to protect human normal colon epithelial cells from mitotic and genomic damages partially by enhancing the function of SAC. PMID:27598149

  1. Physical methods for generating and decoding neural activity in Hirudo verbana

    NASA Astrophysics Data System (ADS)

    Migliori, Benjamin John

    The interface between living nervous systems and hardware is an excellent proving ground for precision experimental methods and information classification systems. Nervous systems are complex (104 -- 10 15(!) connections), fragile, and highly active in intricate, constantly evolving patterns. However, despite the conveniently electrical nature of neural transmission, the interface between nervous systems and hardware poses significant experimental difficulties. As the desire for direct interfaces with neural signals continues to expand, the need for methods of generating and measuring neural activity with high spatiotemporal precision has become increasingly critical. In this thesis, I describe advances I have made in the ability to modify, generate, measure, and understand neural signals both in- and ex-vivo. I focus on methods developed for transmitting and extracting signals in the intact nervous system of Hirudo verbana (the medicinal leech), an animal with a minimally complex nervous system (10000 neurons distributed in packets along a nerve cord) that exhibits a diverse array of behaviors. To introduce artificial activity patterns, I developed a photothermal activation system in which a highly focused laser is used to irradiate carbon microparticles in contact with target neurons. The resulting local temperature increase generates an electrical current that forces the target neuron to fire neural signals, thereby providing a unique neural input mechanism. These neural signals can potentially be used to alter behavioral choice or generate specific behavioral output, and can be used endogenously in many animal models. I also describe new tools developed to expand the application of this method. In complement to this input system, I describe a new method of analyzing neural output signals involved in long-range coordination of behaviors. Leech behavioral signals are propagated between neural packets as electrical pulses in the nerve connective, a bundle of

  2. Neural Encoding of Odors during Active Sampling and in Turbulent Plumes.

    PubMed

    Huston, Stephen J; Stopfer, Mark; Cassenaer, Stijn; Aldworth, Zane N; Laurent, Gilles

    2015-10-21

    Sensory inputs are often fluctuating and intermittent, yet animals reliably utilize them to direct behavior. Here we ask how natural stimulus fluctuations influence the dynamic neural encoding of odors. Using the locust olfactory system, we isolated two main causes of odor intermittency: chaotic odor plumes and active sampling behaviors. Despite their irregularity, chaotic odor plumes still drove dynamic neural response features including the synchronization, temporal patterning, and short-term plasticity of spiking in projection neurons, enabling classifier-based stimulus identification and activating downstream decoders (Kenyon cells). Locusts can also impose odor intermittency through active sampling movements with their unrestrained antennae. Odors triggered immediate, spatially targeted antennal scanning that, paradoxically, weakened individual neural responses. However, these frequent but weaker responses were highly informative about stimulus location. Thus, not only are odor-elicited dynamic neural responses compatible with natural stimulus fluctuations and important for stimulus identification, but locusts actively increase intermittency, possibly to improve stimulus localization. PMID:26456047

  3. The optimization of force inputs for active structural acoustic control using a neural network

    NASA Technical Reports Server (NTRS)

    Cabell, R. H.; Lester, H. C.; Silcox, R. J.

    1992-01-01

    This paper investigates the use of a neural network to determine which force actuators, of a multi-actuator array, are best activated in order to achieve structural-acoustic control. The concept is demonstrated using a cylinder/cavity model on which the control forces, produced by piezoelectric actuators, are applied with the objective of reducing the interior noise. A two-layer neural network is employed and the back propagation solution is compared with the results calculated by a conventional, least-squares optimization analysis. The ability of the neural network to accurately and efficiently control actuator activation for interior noise reduction is demonstrated.

  4. The fiber-optic imaging and manipulation of neural activity during animal behavior.

    PubMed

    Miyamoto, Daisuke; Murayama, Masanori

    2016-02-01

    Recent progress with optogenetic probes for imaging and manipulating neural activity has further increased the relevance of fiber-optic systems for neural circuitry research. Optical fibers, which bi-directionally transmit light between separate sites (even at a distance of several meters), can be used for either optical imaging or manipulating neural activity relevant to behavioral circuitry mechanisms. The method's flexibility and the specifications of the light structure are well suited for following the behavior of freely moving animals. Furthermore, thin optical fibers allow researchers to monitor neural activity from not only the cortical surface but also deep brain regions, including the hippocampus and amygdala. Such regions are difficult to target with two-photon microscopes. Optogenetic manipulation of neural activity with an optical fiber has the advantage of being selective for both cell-types and projections as compared to conventional electrophysiological brain tissue stimulation. It is difficult to extract any data regarding changes in neural activity solely from a fiber-optic manipulation device; however, the readout of data is made possible by combining manipulation with electrophysiological recording, or the simultaneous application of optical imaging and manipulation using a bundle-fiber. The present review introduces recent progress in fiber-optic imaging and manipulation methods, while also discussing fiber-optic system designs that are suitable for a given experimental protocol. PMID:26427958

  5. Neural Activity during Encoding Predicts False Memories Created by Misinformation

    ERIC Educational Resources Information Center

    Okado, Yoko; Stark, Craig E. L.

    2005-01-01

    False memories are often demonstrated using the misinformation paradigm, in which a person's recollection of a witnessed event is altered after exposure to misinformation about the event. The neural basis of this phenomenon, however, remains unknown. The authors used fMRI to investigate encoding processes during the viewing of an event and…

  6. Neural correlates of aberrant emotional salience predict psychotic symptoms and global functioning in high-risk and first-episode psychosis.

    PubMed

    Modinos, Gemma; Tseng, Huai-Hsuan; Falkenberg, Irina; Samson, Carly; McGuire, Philip; Allen, Paul

    2015-10-01

    Neurobiological and behavioral findings suggest that psychosis is associated with corticolimbic hyperactivity during the processing of emotional salience. This has not been widely studied in the early stages of psychosis, and the impact of these abnormalities on psychotic symptoms and global functioning is unknown. We sought to address this issue in 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs). Corticolimbic response and subjective ratings to emotional and neutral scenes were measured using functional magnetic resonance imaging. The clinical and functional impact of corticolimbic abnormalities was assessed with regression analyses. The FEP and UHR groups reported increased subjective emotional arousal to neutral scenes compared with HCs. Across groups, emotional vs neutral scenes elicited activation in the dorsomedial prefrontal cortex, inferior frontal gyrus/anterior insula and amygdala. Although FEP and UHR participants showed reduced activation in these regions when viewing emotional scenes compared with controls, this was driven by increased activation to neutral scenes. Corticolimbic hyperactivity to neutral scenes predicted higher levels of positive symptoms and poorer levels of functioning. These results indicate that disruption of emotional brain systems may represent an important biological substrate for the pathophysiology of early psychosis and UHR states. PMID:25809400

  7. An ATF/CREB binding motif is required for aberrant constitutive expression of the MHC class II DR alpha promoter and activation by SV40 T-antigen.

    PubMed Central

    Cox, P M; Goding, C R

    1992-01-01

    Constitutive expression of major histocompatibility complex class II (MHC II) antigens normally occurs in B-lymphocytes and antigen presenting cells of the monocyte/macrophage lineage. However, many malignant tumours and transformed cells express these proteins aberrantly. We demonstrate here that the MHC II DR alpha promoter is constitutively active both in the SV40 large T antigen transformed cell line, COS, and in CV1 cells from which they are derived. As an approach to understanding the molecular mechanisms underlying aberrant DR alpha expression we have examined the cis- and trans-acting requirements for DR alpha transcription in these cell types. Electrophoretic mobility shift assays showed that the region immediately 3' to the X-box was bound by a member of the ATF/CREB family of transcription factors. Using deletions and point mutations in the DR alpha promoter we demonstrate that, in contrast to B-cells, the octamer motif and conserved X- and Y-boxes make only a minor contribution to promoter function while single point mutations in the ATF/CREB motif reduced transcription up to 20-fold. In addition, we show that the DR alpha promoter is activated by SV40 large T-antigen and that activation requires an intact ATF/CREB motif. Similar data were obtained using B16 melanoma cells. These results suggest that the ATF/CREB motif may be a target for transcription deregulation in several transformed cell types. Images PMID:1329030

  8. High baseline activity in inferior temporal cortex improves neural and behavioral discriminability during visual categorization

    PubMed Central

    Emadi, Nazli; Rajimehr, Reza; Esteky, Hossein

    2014-01-01

    Spontaneous firing is a ubiquitous property of neural activity in the brain. Recent literature suggests that this baseline activity plays a key role in perception. However, it is not known how the baseline activity contributes to neural coding and behavior. Here, by recording from the single neurons in the inferior temporal cortex of monkeys performing a visual categorization task, we thoroughly explored the relationship between baseline activity, the evoked response, and behavior. Specifically we found that a low-frequency (<8 Hz) oscillation in the spike train, prior and phase-locked to the stimulus onset, was correlated with increased gamma power and neuronal baseline activity. This enhancement of the baseline activity was then followed by an increase in the neural selectivity and the response reliability and eventually a higher behavioral performance. PMID:25404900

  9. Interpreting Chromosome Aberration Spectra

    NASA Technical Reports Server (NTRS)

    Levy, Dan; Reeder, Christopher; Loucas, Bradford; Hlatky, Lynn; Chen, Allen; Cornforth, Michael; Sachs, Rainer

    2007-01-01

    Ionizing radiation can damage cells by breaking both strands of DNA in multiple locations, essentially cutting chromosomes into pieces. The cell has enzymatic mechanisms to repair such breaks; however, these mechanisms are imperfect and, in an exchange process, may produce a large-scale rearrangement of the genome, called a chromosome aberration. Chromosome aberrations are important in killing cells, during carcinogenesis, in characterizing repair/misrepair pathways, in retrospective radiation biodosimetry, and in a number of other ways. DNA staining techniques such as mFISH ( multicolor fluorescent in situ hybridization) provide a means for analyzing aberration spectra by examining observed final patterns. Unfortunately, an mFISH observed final pattern often does not uniquely determine the underlying exchange process. Further, resolution limitations in the painting protocol sometimes lead to apparently incomplete final patterns. We here describe an algorithm for systematically finding exchange processes consistent with any observed final pattern. This algorithm uses aberration multigraphs, a mathematical formalism that links the various aspects of aberration formation. By applying a measure to the space of consistent multigraphs, we will show how to generate model-specific distributions of aberration processes from mFISH experimental data. The approach is implemented by software freely available over the internet. As a sample application, we apply these algorithms to an aberration data set, obtaining a distribution of exchange cycle sizes, which serves to measure aberration complexity. Estimating complexity, in turn, helps indicate how damaging the aberrations are and may facilitate identification of radiation type in retrospective biodosimetry.

  10. A point process framework for relating neural spiking activity to spiking history, neural ensemble, and extrinsic covariate effects.

    PubMed

    Truccolo, Wilson; Eden, Uri T; Fellows, Matthew R; Donoghue, John P; Brown, Emery N

    2005-02-01

    Multiple factors simultaneously affect the spiking activity of individual neurons. Determining the effects and relative importance of these factors is a challenging problem in neurophysiology. We propose a statistical framework based on the point process likelihood function to relate a neuron's spiking probability to three typical covariates: the neuron's own spiking history, concurrent ensemble activity, and extrinsic covariates such as stimuli or behavior. The framework uses parametric models of the conditional intensity function to define a neuron's spiking probability in terms of the covariates. The discrete time likelihood function for point processes is used to carry out model fitting and model analysis. We show that, by modeling the logarithm of the conditional intensity function as a linear combination of functions of the covariates, the discrete time point process likelihood function is readily analyzed in the generalized linear model (GLM) framework. We illustrate our approach for both GLM and non-GLM likelihood functions using simulated data and multivariate single-unit activity data simultaneously recorded from the motor cortex of a monkey performing a visuomotor pursuit-tracking task. The point process framework provides a flexible, computationally efficient approach for maximum likelihood estimation, goodness-of-fit assessment, residual analysis, model selection, and neural decoding. The framework thus allows for the formulation and analysis of point process models of neural spiking activity that readily capture the simultaneous effects of multiple covariates and enables the assessment of their relative importance. PMID:15356183

  11. Explorative data analysis for changes in neural activity

    NASA Astrophysics Data System (ADS)

    Blythe, Duncan A. J.; Meinecke, Frank C.; von Bünau, Paul; Müller, Klaus-Robert

    2013-04-01

    Neural recordings are non-stationary time series, i.e. their properties typically change over time. Identifying specific changes, e.g., those induced by a learning task, can shed light on the underlying neural processes. However, such changes of interest are often masked by strong unrelated changes, which can be of physiological origin or due to measurement artifacts. We propose a novel algorithm for disentangling such different causes of non-stationarity and in this manner enable better neurophysiological interpretation for a wider set of experimental paradigms. A key ingredient is the repeated application of Stationary Subspace Analysis (SSA) using different temporal scales. The usefulness of our explorative approach is demonstrated in simulations, theory and EEG experiments with 80 brain-computer interfacing subjects.

  12. A role for correlated spontaneous activity in the assembly of neural circuits

    PubMed Central

    Kirkby, Lowry; Sack, Georgeann; Firl, Alana; Feller, Marla B.

    2015-01-01

    Before the onset of sensory transduction, developing neural circuits spontaneously generate correlated activity in distinct spatial and temporal patterns. During this period of patterned activity, sensory maps develop and initial coarse connections are refined, which are critical steps in the establishment of adult neural circuits. Over the last decade there has been substantial evidence that altering the pattern of spontaneous activity disrupts refinement, but the mechanistic understanding of this process remains incomplete. In this review, we discuss recent experimental and theoretical progress towards the process of activity-dependent refinement, focusing on circuits in the visual, auditory and motor systems. While many outstanding questions remain, the combination of several novel approaches have brought us closer to a comprehensive understanding of how complex neural circuits are established by patterned spontaneous activity during development. PMID:24314725

  13. The MEG topography and the source model of abnormal neural activities associated with brain lesions

    SciTech Connect

    Ueno, S.; Iramina, K.; Ozaki, H.; Harada, K.

    1986-09-01

    A source model is proposed to simulate spatial distributions of abnormal MEG and EEG activities generated by abnormal neural activities such as the delta activity associated with brain tumors. Brain tumor itself is electrically silent and the spherical shell around the tumor might generate abnormal neural activities. The sources of these neural activities are represented by combinations of multiple current dipoles. The head is assumed to be a spherical volume conductor. Electrical potentials and magnetic fields over the surface of the spheres are calculated. The computer simulation shows that the MEG topography and EEG topography vary variously with combinations of location and orientation of the dipoles. In a special case, however, that the dipoles orient in the same direction or orient radially, the spatial patterns of the MEGs and EEGs generated by numerous dipoles are analogous to those generated by single dipoles.

  14. Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex.

    PubMed

    Devor, Anna; Dunn, Andrew K; Andermann, Mark L; Ulbert, Istvan; Boas, David A; Dale, Anders M

    2003-07-17

    Recent advances in brain imaging techniques, including functional magnetic resonance imaging (fMRI), offer great promise for noninvasive mapping of brain function. However, the indirect nature of the imaging signals to the underlying neural activity limits the interpretation of the resulting maps. The present report represents the first systematic study with sufficient statistical power to quantitatively characterize the relationship between changes in blood oxygen content and the neural spiking and synaptic activity. Using two-dimensional optical measurements of hemodynamic signals, simultaneous recordings of neural activity, and an event-related stimulus paradigm, we demonstrate that (1) there is a strongly nonlinear relationship between electrophysiological measures of neuronal activity and the hemodynamic response, (2) the hemodynamic response continues to grow beyond the saturation of electrical activity, and (3) the initial increase in deoxyhemoglobin that precedes an increase in blood volume is counterbalanced by an equal initial decrease in oxyhemoglobin. PMID:12873390

  15. Early neural activation during facial affect processing in adolescents with Autism Spectrum Disorder☆

    PubMed Central

    Leung, Rachel C.; Pang, Elizabeth W.; Cassel, Daniel; Brian, Jessica A.; Smith, Mary Lou; Taylor, Margot J.

    2014-01-01

    Impaired social interaction is one of the hallmarks of Autism Spectrum Disorder (ASD). Emotional faces are arguably the most critical visual social stimuli and the ability to perceive, recognize, and interpret emotions is central to social interaction and communication, and subsequently healthy social development. However, our understanding of the neural and cognitive mechanisms underlying emotional face processing in adolescents with ASD is limited. We recruited 48 adolescents, 24 with high functioning ASD and 24 typically developing controls. Participants completed an implicit emotional face processing task in the MEG. We examined spatiotemporal differences in neural activation between the groups during implicit angry and happy face processing. While there were no differences in response latencies between groups across emotions, adolescents with ASD had lower accuracy on the implicit emotional face processing task when the trials included angry faces. MEG data showed atypical neural activity in adolescents with ASD during angry and happy face processing, which included atypical activity in the insula, anterior and posterior cingulate and temporal and orbitofrontal regions. Our findings demonstrate differences in neural activity during happy and angry face processing between adolescents with and without ASD. These differences in activation in social cognitive regions may index the difficulties in face processing and in comprehension of social reward and punishment in the ASD group. Thus, our results suggest that atypical neural activation contributes to impaired affect processing, and thus social cognition, in adolescents with ASD. PMID:25610782

  16. Fractal Patterns of Neural Activity Exist within the Suprachiasmatic Nucleus and Require Extrinsic Network Interactions

    PubMed Central

    Hu, Kun; Meijer, Johanna H.; Shea, Steven A.; vanderLeest, Henk Tjebbe; Pittman-Polletta, Benjamin; Houben, Thijs; van Oosterhout, Floor; Deboer, Tom; Scheer, Frank A. J. L.

    2012-01-01

    The mammalian central circadian pacemaker (the suprachiasmatic nucleus, SCN) contains thousands of neurons that are coupled through a complex network of interactions. In addition to the established role of the SCN in generating rhythms of ∼24 hours in many physiological functions, the SCN was recently shown to be necessary for normal self-similar/fractal organization of motor activity and heart rate over a wide range of time scales—from minutes to 24 hours. To test whether the neural network within the SCN is sufficient to generate such fractal patterns, we studied multi-unit neural activity of in vivo and in vitro SCNs in rodents. In vivo SCN-neural activity exhibited fractal patterns that are virtually identical in mice and rats and are similar to those in motor activity at time scales from minutes up to 10 hours. In addition, these patterns remained unchanged when the main afferent signal to the SCN, namely light, was removed. However, the fractal patterns of SCN-neural activity are not autonomous within the SCN as these patterns completely broke down in the isolated in vitro SCN despite persistence of circadian rhythmicity. Thus, SCN-neural activity is fractal in the intact organism and these fractal patterns require network interactions between the SCN and extra-SCN nodes. Such a fractal control network could underlie the fractal regulation observed in many physiological functions that involve the SCN, including motor control and heart rate regulation. PMID:23185285

  17. An aberrant precision account of autism

    PubMed Central

    Lawson, Rebecca P.; Rees, Geraint; Friston, Karl J.

    2014-01-01

    Autism is a neurodevelopmental disorder characterized by problems with social-communication, restricted interests and repetitive behavior. A recent and thought-provoking article presented a normative explanation for the perceptual symptoms of autism in terms of a failure of Bayesian inference (Pellicano and Burr, 2012). In response, we suggested that when Bayesian inference is grounded in its neural instantiation—namely, predictive coding—many features of autistic perception can be attributed to aberrant precision (or beliefs about precision) within the context of hierarchical message passing in the brain (Friston et al., 2013). Here, we unpack the aberrant precision account of autism. Specifically, we consider how empirical findings—that speak directly or indirectly to neurobiological mechanisms—are consistent with the aberrant encoding of precision in autism; in particular, an imbalance of the precision ascribed to sensory evidence relative to prior beliefs. PMID:24860482

  18. Real-time Neural Network predictions of geomagnetic activity indices

    NASA Astrophysics Data System (ADS)

    Bala, R.; Reiff, P. H.

    2009-12-01

    The Boyle potential or the Boyle Index (BI), Φ (kV)=10-4 (V/(km/s))2 + 11.7 (B/nT) sin3(θ/2), is an empirically-derived formula that can characterize the Earth's polar cap potential, which is readily derivable in real time using the solar wind data from ACE (Advanced Composition Explorer). The BI has a simplistic form that utilizes a non-magnetic "viscous" and a magnetic "merging" component to characterize the magnetospheric behavior in response to the solar wind. We have investigated its correlation with two of conventional geomagnetic activity indices in Kp and the AE index. We have shown that the logarithms of both 3-hr and 1-hr averages of the BI correlate well with the subsequent Kp: Kp = 8.93 log10(BI) - 12.55 along with 1-hr BI correlating with the subsequent log10(AE): log10(AE) = 1.78 log10(BI) - 3.6. We have developed a new set of algorithms based on Artificial Neural Networks (ANNs) suitable for short term space weather forecasts with an enhanced lead-time and better accuracy in predicting Kp and AE over some leading models; the algorithms omit the time history of its targets to utilize only the solar wind data. Inputs to our ANN models benefit from the BI and its proven record as a forecasting parameter since its initiation in October, 2003. We have also performed time-sensitivity tests using cross-correlation analysis to demonstrate that our models are as efficient as those that incorporates the time history of the target indices in their inputs. Our algorithms can predict the upcoming full 3-hr Kp, purely from the solar wind data and achieve a linear correlation coefficient of 0.840, which means that it predicts the upcoming Kp value on average to within 1.3 step, which is approximately the resolution of the real-time Kp estimate. Our success in predicting Kp during a recent unexpected event (22 July ’09) is shown in the figure. Also, when predicting an equivalent "one hour Kp'', the correlation coefficient is 0.86, meaning on average a prediction

  19. Perceptual similarity of visual patterns predicts dynamic neural activation patterns measured with MEG.

    PubMed

    Wardle, Susan G; Kriegeskorte, Nikolaus; Grootswagers, Tijl; Khaligh-Razavi, Seyed-Mahdi; Carlson, Thomas A

    2016-05-15

    Perceptual similarity is a cognitive judgment that represents the end-stage of a complex cascade of hierarchical processing throughout visual cortex. Previous studies have shown a correspondence between the similarity of coarse-scale fMRI activation patterns and the perceived similarity of visual stimuli, suggesting that visual objects that appear similar also share similar underlying patterns of neural activation. Here we explore the temporal relationship between the human brain's time-varying representation of visual patterns and behavioral judgments of perceptual similarity. The visual stimuli were abstract patterns constructed from identical perceptual units (oriented Gabor patches) so that each pattern had a unique global form or perceptual 'Gestalt'. The visual stimuli were decodable from evoked neural activation patterns measured with magnetoencephalography (MEG), however, stimuli differed in the similarity of their neural representation as estimated by differences in decodability. Early after stimulus onset (from 50ms), a model based on retinotopic organization predicted the representational similarity of the visual stimuli. Following the peak correlation between the retinotopic model and neural data at 80ms, the neural representations quickly evolved so that retinotopy no longer provided a sufficient account of the brain's time-varying representation of the stimuli. Overall the strongest predictor of the brain's representation was a model based on human judgments of perceptual similarity, which reached the limits of the maximum correlation with the neural data defined by the 'noise ceiling'. Our results show that large-scale brain activation patterns contain a neural signature for the perceptual Gestalt of composite visual features, and demonstrate a strong correspondence between perception and complex patterns of brain activity. PMID:26899210

  20. Altered Neural Activity Associated with Mindfulness during Nociception: A Systematic Review of Functional MRI

    PubMed Central

    Bilevicius, Elena; Kolesar, Tiffany A.; Kornelsen, Jennifer

    2016-01-01

    Objective: To assess the neural activity associated with mindfulness-based alterations of pain perception. Methods: The Cochrane Central, EMBASE, Ovid Medline, PsycINFO, Scopus, and Web of Science databases were searched on 2 February 2016. Titles, abstracts, and full-text articles were independently screened by two reviewers. Data were independently extracted from records that included topics of functional neuroimaging, pain, and mindfulness interventions. Results: The literature search produced 946 total records, of which five met the inclusion criteria. Records reported pain in terms of anticipation (n = 2), unpleasantness (n = 5), and intensity (n = 5), and how mindfulness conditions altered the neural activity during noxious stimulation accordingly. Conclusions: Although the studies were inconsistent in relating pain components to neural activity, in general, mindfulness was able to reduce pain anticipation and unpleasantness ratings, as well as alter the corresponding neural activity. The major neural underpinnings of mindfulness-based pain reduction consisted of altered activity in the anterior cingulate cortex, insula, and dorsolateral prefrontal cortex. PMID:27104572

  1. An event-related examination of neural activity during social interactions

    PubMed Central

    Khatcherian, Stephanie M.; Ball, Aaron B.; Rosen, Peter J.

    2013-01-01

    Social exclusion is known to cause alterations in neural activity and perceptions of social distress. However, previous research is largely limited to examining social interactions as a unitary phenomenon without investigating adjustments in neural and attentional processes that occur during social interactions. To address this limitation, we examined neural activity on a trial-by-trial basis during different social interactions. Our results show conflict monitoring neural alarm activation, indexed by the N2, in response to specific exclusionary events; even during interactions that are inclusionary overall and in the absence of self-reported feelings of social pain. Furthermore, we show enhanced attentional activation to exclusionary events, indexed by the P3b, during exclusionary, compared with inclusionary, interactions, and this P3b activation was associated with self-reported social distress following prolonged social exclusion. Finally, both the N2 and P3b showed larger amplitudes in the earlier stages of exclusion compared with later stages, suggesting heightened early sensitivity for both components. Together, these findings provide novel insights into the dynamic neural and perceptual processes of exclusion that exist during social interactions and the relationship between discrete events within interactions and the more general contexts of the social interactions. PMID:22577169

  2. Two-stage neural algorithm for defect detection and characterization uses an active thermography

    NASA Astrophysics Data System (ADS)

    Dudzik, Sebastian

    2015-07-01

    In the paper a two-stage neural algorithm for defect detection and characterization is presented. In order to estimate the defect depth two neural networks trained on data obtained using an active thermography were employed. The first stage of the algorithm is developed to detect the defect by a classification neural network. Then the defects depth is estimated using a regressive neural network. In this work the results of experimental investigations and simulations are shown. Further, the sensitivity analysis of the presented algorithm was conducted and the impacts of emissivity error and the ambient temperature error on the depth estimation errors were studied. The results were obtained using a test sample made of material with a low thermal diffusivity.

  3. Epigenetic activation of Sox2 gene in the developing vertebrate neural plate

    PubMed Central

    Bouzas, Santiago O.; Marini, Melisa S.; Torres Zelada, Eliana; Buzzi, Ailín L.; Morales Vicente, David A.; Strobl-Mazzulla, Pablo H.

    2016-01-01

    One of the earliest manifestations of neural induction is onset of expression of the neural marker Sox2, mediated by the activation of the enhancers N1 and N2. By using loss and gain of function, we find that Sox2 expression requires the activity of JmjD2A and the Msk1 kinase, which can respectively demethylate the repressive H3K9me3 mark and phosphorylate the activating H3S10 (H3S10ph) mark. Bimolecular fluorescence complementation reveals that the adaptor protein 14-3-3, known to bind to H3S10ph, interacts with JMJD2A and may be involved in its recruitment to regulatory regions of the Sox2 gene. Chromatin immunoprecipitation reveals dynamic binding of JMJD2A to the Sox2 promoter and N-1 enhancer at the time of neural plate induction. Finally, we show a clear temporal antagonism on the occupancy of H3K9me3 and H3S10ph modifications at the promoter of the Sox2 locus before and after the neural plate induction. Taken together, our results propose a series of epigenetic events necessary for the early activation of the Sox2 gene in neural progenitor cells. PMID:27099369

  4. Epigenetic activation of Sox2 gene in the developing vertebrate neural plate.

    PubMed

    Bouzas, Santiago O; Marini, Melisa S; Torres Zelada, Eliana; Buzzi, Ailín L; Morales Vicente, David A; Strobl-Mazzulla, Pablo H

    2016-06-15

    One of the earliest manifestations of neural induction is onset of expression of the neural marker Sox2, mediated by the activation of the enhancers N1 and N2. By using loss and gain of function, we find that Sox2 expression requires the activity of JmjD2A and the Msk1 kinase, which can respectively demethylate the repressive H3K9me3 mark and phosphorylate the activating H3S10 (H3S10ph) mark. Bimolecular fluorescence complementation reveals that the adaptor protein 14-3-3, known to bind to H3S10ph, interacts with JMJD2A and may be involved in its recruitment to regulatory regions of the Sox2 gene. Chromatin immunoprecipitation reveals dynamic binding of JMJD2A to the Sox2 promoter and N-1 enhancer at the time of neural plate induction. Finally, we show a clear temporal antagonism on the occupancy of H3K9me3 and H3S10ph modifications at the promoter of the Sox2 locus before and after the neural plate induction. Taken together, our results propose a series of epigenetic events necessary for the early activation of the Sox2 gene in neural progenitor cells. PMID:27099369

  5. Feasibility of Neural Stimulation With Floating-Light-Activated Microelectrical Stimulators

    PubMed Central

    Abdo, Ammar; Sahin, Mesut

    2011-01-01

    Neural microstimulation is becoming a powerful tool for the restoration of impaired functions in the central nervous system. Microelectrode arrays with fine wire interconnects have traditionally been used in the development of these neural prosthetic devices. However, these interconnects are usually the most vulnerable part of the neuroprosthetic implant that can eventually cause the device to fail. In this paper, we investigate the feasibility of floating-light-activated microelectrical stimulators (FLAMES) for wireless neural stimulation. A computer model was developed to simulate the micro stimulators for typical requirements of neural activation in the human white and gray matters. First, the photon densities due to a circular laser beam were simulated in the neural tissue at near-infrared (NIR) wavelengths. Temperature elevation in the tissue was calculated and the laser power was retrospectively adjusted to 325 and 250 mW/cm2 in the gray and white matters, respectively, to limit ΔT to 0.5 °C. Total device area of the FLAMES increased with all parameters considered but decreased with the output voltage. We conclude that the number of series photodiodes in the device can be used as a free parameter to minimize the device size. The results suggest that floating, optically activated stimulators are feasible at submillimeter sizes for the activation of the brain cortex or the spinal cord. PMID:21552457

  6. Neural Activation Underlying Cognitive Control in the Context of Neutral and Affectively Charged Pictures in Children

    ERIC Educational Resources Information Center

    Lamm, Connie; White, Lauren K.; McDermott, Jennifer Martin; Fox, Nathan A.

    2012-01-01

    The neural correlates of cognitive control for typically developing 9-year-old children were examined using dense-array ERPs and estimates of cortical activation (LORETA) during a go/no-go task with two conditions: a neutral picture condition and an affectively charged picture condition. Activation was estimated for the entire cortex after which…

  7. Transform-invariant feature based functional MR image registration and neural activity modelling.

    PubMed

    Gong, Jiaqi; Hao, Qi; Hu, Fei

    2013-01-01

    In this paper, a set of non-rigid image registration and neural activity modelling methods using functional MR Images (fMRI) are proposed based on transform-invariant feature representations. Our work made two contributions. First, we propose to use a transform-invariant feature to improve image registration performance of Iterative Closest Point (ICP) based methods. The proposed feature utilises Gaussian Mixture Models (GMM) to describe the local topological structure of fMRI data. Second, we propose to use a 3-dimensional Scale-Invariant Feature Transform (SIFT) based descriptor to represent neural activities related to drinking behaviour. As a result, neural activities patterns of different subjects drinking water or intaking glucose can be recognised, with strong robustness against various artefacts. PMID:23900434

  8. Sensorimotor Encoding by Synchronous Neural Ensemble Activity at Multiple Levels of the Somatosensory System

    NASA Astrophysics Data System (ADS)

    Nocolelis, Miguel A. L.; Baccala, Luiz A.; Lin, Rick C. S.; Chapin, John K.

    1995-06-01

    Neural ensemble processing of sensorimotor information during behavior was investigated by simultaneously recording up to 48 single neurons at multiple relays of the rat trigeminal somatosensory system. Cortical, thalamic, and brainstem neurons exhibited widespread 7- to 12-hertz synchronous oscillations, which began during attentive immobility and reliably predicted the imminent onset of rhythmic whisker twitching. Each oscillatory cycle began as a traveling wave of neural activity in the cortex that then spread to the thalamus. Just before the onset of rhythmic whisker twitching, the oscillations spread to the spinal trigeminal brainstem complex. Thereafter, the oscillations at all levels were synchronous with whisker protraction. Neural structures manifesting these rhythms also exhibited distributed spatiotemporal patterns of neuronal ensemble activity in response to tactile stimulation. Thus, multilevel synchronous activity in this system may encode not only sensory information but also the onset and temporal domain of tactile exploratory movements.

  9. Increased Neural Activation during Picture Encoding and Retrieval in 60-Year-Olds Compared to 20-Year-Olds

    ERIC Educational Resources Information Center

    Burgmans, S.; van Boxtel, M. P. J.; Vuurman, E. F. P. M.; Evers, E. A. T.; Jolles, J.

    2010-01-01

    Brain aging has been associated with both reduced and increased neural activity during task execution. The purpose of the present study was to investigate whether increased neural activation during memory encoding and retrieval is already present at the age of 60 as well as to obtain more insight into the mechanism behind increased activity.…

  10. Antitumor activity of the β-glucan paramylon from Euglena against preneoplastic colonic aberrant crypt foci in mice.

    PubMed

    Watanabe, Toshiaki; Shimada, Ryoko; Matsuyama, Ai; Yuasa, Masahiro; Sawamura, Hiromi; Yoshida, Eriko; Suzuki, Kengo

    2013-11-01

    In the present study, the effects of β-glucans isolated from Euglena on the formation of preneoplastic aberrant crypt foci (ACF) in the colon were examined in mice. Mice were fed a semi-purified AIN-93M diet containing cellulose or the same diet but with the cellulose replaced with β-glucans in the form of Euglena, paramylon, or amorphous paramylon, for 11 weeks. After consuming these dietary supplements for 8 days, half of the mice were intraperitoneally administered 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) body weight every week for 6 weeks. Among the DMH-treated groups, the paramylon- and amorphous paramylon-fed mice displayed a significantly lower number of ACF than the control group. Also, the liver weight of the paramylon group was markedly decreased compared with those of the control and Euglena groups, whereas the cecal content weight and fecal volume of the paramylon group were significantly increased. As for the levels of organic acids in the cecal contents, the paramylon group displayed significantly increased lactic acid levels compared with the control and Euglena groups. From these findings, although the mechanism of the ACF-inhibiting effects of paramylon remains unclear, it is considered that β-glucans, such as paramylon and its isomer amorphous paramylon, have preventive effects against colon cancer and are more effective against the condition than Euglena. PMID:24104447

  11. Aberrant hepatic processing causes removal of activation peptide and primary polymerisation site from fibrinogen Canterbury (A alpha 20 Val --> Asp).

    PubMed Central

    Brennan, S O; Hammonds, B; George, P M

    1995-01-01

    A novel mechanism of molecular disease was uncovered in a patient with prolonged thrombin time and a mild bleeding tendency. DNA sequencing of the fibrinogen A alpha chain indicated heterozygosity for a mutation of 20 Val --> Asp. The molar ratio of fibrinopeptide A to B released by thrombin was substantially reduced at 0.64 suggesting either impaired cleavage or that the majority of the variant alpha chains lacked the A peptide. The latter novel proposal arises from the observation that the mutation changes the normal 16R G P R V20 sequence to R G P R D creating a potential furin cleavage site at Arg 19. Synthetic peptides incorporating both sequences were tested as substrates for both thrombin and furin. There was no substantial difference in the thrombin catalyzed cleavage. However, the variant peptide, but not the normal, was rapidly cleaved at Arg 19 by furin. Predictably intracellular cleavage of the Aalpha-chain at Arg 19 would remove fibrinopeptide A together with the G P R polymerisation site. This was confirmed by sequence analysis of fibrinogen Aalpha chains after isolation by SDS-PAGE. The expected normal sequence was detected together with a new sequence (D V E R H Q S A-) commencing at residue 20. Truncation was further verified by nonreducing SDS-PAGE of the NH2-terminal disulfide knot which indicated the presence of aberrant homo- and heterodimers. Images PMID:8675656

  12. Effects of a genome-wide supported psychosis risk variant on neural activation during a theory-of-mind task.

    PubMed

    Walter, H; Schnell, K; Erk, S; Arnold, C; Kirsch, P; Esslinger, C; Mier, D; Schmitgen, M M; Rietschel, M; Witt, S H; Nöthen, M M; Cichon, S; Meyer-Lindenberg, A

    2011-04-01

    Schizophrenia is associated with marked deficits in theory of mind (ToM), a higher-order form of social cognition representing the thoughts, emotions and intentions of others. Altered brain activation in the medial prefrontal cortex and temporo-parietal cortex during ToM tasks has been found in patients with schizophrenia, but the relevance of these neuroimaging findings for the heritable risk for schizophrenia is unclear. We tested the hypothesis that activation of the ToM network is altered in healthy risk allele carriers of the single-nucleotide polymorphism rs1344706 in the gene ZNF804A, a recently discovered risk variant for psychosis with genome-wide support. In all, 109 healthy volunteers of both sexes in Hardy-Weinberg equilibrium for rs1344706 were investigated with functional magnetic resonance imaging during a ToM task. As hypothesised, risk carriers exhibited a significant (P<0.05 false discovery rate, corrected for multiple comparisons) risk allele dose effect on neural activity in the medial prefrontal cortex and left temporo-parietal cortex. Moreover, the same effect was found in the left inferior parietal cortex and left inferior frontal cortex, which are part of the human analogue of the mirror neuron system. In addition, in an exploratory analysis (P<0.001 uncorrected), we found evidence for aberrant functional connectivity between the frontal and temporo-parietal regions in risk allele carriers. To conclude, we show that a dysfunction of the ToM network is associated with a genome-wide supported genetic risk variant for schizophrenia and has promise as an intermediate phenotype that can be mined for the development of biological interventions targeted to social dysfunction in psychiatry. PMID:20231838

  13. GABAergic neural activity involved in salicylate-induced auditory cortex gain enhancement.

    PubMed

    Lu, J; Lobarinas, E; Deng, A; Goodey, R; Stolzberg, D; Salvi, R J; Sun, W

    2011-08-25

    Although high doses of sodium salicylate impair cochlear function, it paradoxically enhances sound-evoked activity in the auditory cortex (AC) and augments acoustic startle reflex responses, neural and behavioral metrics associated with hyperexcitability and hyperacusis. To explore the neural mechanisms underlying salicylate (SS)-induced hyperexcitability and "increased central gain," we examined the effects of GABA receptor agonists and antagonists on SS-induced hyperexcitability in the AC and startle reflex responses. Consistent with our previous findings, local or systemic application of SS significantly increased the amplitude of sound-evoked AC neural activity, but generally reduced spontaneous activity in the AC. Systemic injection of SS also significantly increased the acoustic startle reflex. S-baclofen or R-baclofen, GABA-B agonists, which suppressed sound-evoked AC neural firing rate and local field potentials, also suppressed the SS-induced enhancement of the AC field potential and the acoustic startle reflex. Local application of vigabatrin, which enhances GABA concentration in the brain, suppressed the SS-induced enhancement of AC firing rate. Systemic injection of vigabatrin also reduced the SS-induced enhancement of acoustic startle reflex. Collectively, these results suggest that the sound-evoked behavioral and neural hyperactivity induced by SS may arise from a SS-induced suppression of GABAergic inhibition in the AC. PMID:21664433

  14. Neural Activation During Submaximal Contractions Seems More Reflective of Neuromuscular Ageing than Maximal Voluntary Activation

    PubMed Central

    Scaglioni, Gil; Narici, Marco V.; Martin, Alain

    2016-01-01

    This study aimed at testing the hypothesis that differences in neural activation strategy during submaximal but not maximal plantarflexions exist between young and older men. Eleven young men (YM, 26 ± 4 years) and thirteen old men (OM, 76 ± 3 years) volunteered for the investigation. Maximal voluntary torque (MVT) was 38.2%, lower (p < 0.001) in OM than in YM, while voluntary activation was equivalent (~97%). The relationship between the interpolated twitch-torque and the voluntary torque (IT-VT relationship) was composite (curvilinear + exponential) for both age-groups. However, the OM showed accentuated concavity, as attested by the occurrence of the deviation from linearity at a lower contraction intensity (OM: 54.9 vs. YM: 71.9% MVT). In conclusion, ageing does not affect the capacity to fully activate the plantar flexors during maximal performances, but it alters the activation pattern for submaximal levels of effort. The greater age-related concavity of the IT-VT relationship suggests that, during submaximal contractions, OM need to reach a level of activation higher than YM to develop an equivalent relative torque. PMID:26941638

  15. Information content of neural networks with self-control and variable activity

    NASA Astrophysics Data System (ADS)

    Bollé, D.; Amari, S. I.; Dominguez Carreta, D. R. C.; Massolo, G.

    2001-02-01

    A self-control mechanism for the dynamics of neural networks with variable activity is discussed using a recursive scheme for the time evolution of the local field. It is based upon the introduction of a self-adapting time-dependent threshold as a function of both the neural and pattern activity in the network. This mechanism leads to an improvement of the information content of the network as well as an increase of the storage capacity and the basins of attraction. Different architectures are considered and the results are compared with numerical simulations.

  16. Modeling neural circuits in Parkinson's disease.

    PubMed

    Psiha, Maria; Vlamos, Panayiotis

    2015-01-01

    Parkinson's disease (PD) is caused by abnormal neural activity of the basal ganglia which are connected to the cerebral cortex in the brain surface through complex neural circuits. For a better understanding of the pathophysiological mechanisms of PD, it is important to identify the underlying PD neural circuits, and to pinpoint the precise nature of the crucial aberrations in these circuits. In this paper, the general architecture of a hybrid Multilayer Perceptron (MLP) network for modeling the neural circuits in PD is presented. The main idea of the proposed approach is to divide the parkinsonian neural circuitry system into three discrete subsystems: the external stimuli subsystem, the life-threatening events subsystem, and the basal ganglia subsystem. The proposed model, which includes the key roles of brain neural circuit in PD, is based on both feed-back and feed-forward neural networks. Specifically, a three-layer MLP neural network with feedback in the second layer was designed. The feedback in the second layer of this model simulates the dopamine modulatory effect of compacta on striatum. PMID:25416983

  17. The Aberration Corrected SEM

    SciTech Connect

    Joy, David C.

    2005-09-09

    The performance of the conventional low-energy CD-SEM is limited by the aberrations inherent in the probe forming lens. Multi-pole correctors are now available which can reduce or eliminate these aberrations. An SEM equipped with such a corrector offers higher spatial resolution and more probe current from a given electron source, and other aspects of the optical performance are also improved, but the much higher numerical aperture associated with an aberration corrected lens results in a reduction in imaging depth of field.

  18. 12-Deoxyphorbols Promote Adult Neurogenesis by Inducing Neural Progenitor Cell Proliferation via PKC Activation

    PubMed Central

    Geribaldi-Doldán, Noelia; Flores-Giubi, Eugenia; Murillo-Carretero, Maribel; García-Bernal, Francisco; Carrasco, Manuel; Macías-Sánchez, Antonio J.; Domínguez-Riscart, Jesús; Verástegui, Cristina; Hernández-Galán, Rosario

    2016-01-01

    Background: Neuropsychiatric and neurological disorders frequently occur after brain insults associated with neuronal loss. Strategies aimed to facilitate neuronal renewal by promoting neurogenesis constitute a promising therapeutic option to treat neuronal death-associated disorders. In the adult brain, generation of new neurons occurs physiologically throughout the entire life controlled by extracellular molecules coupled to intracellular signaling cascades. Proteins participating in these cascades within neurogenic regions constitute potential pharmacological targets to promote neuronal regeneration of injured areas of the central nervous system. Methodology: We have performed in vitro and in vivo approaches to determine neural progenitor cell proliferation to understand whether activation of kinases of the protein kinase C family facilitates neurogenesis in the adult brain. Results: We have demonstrated that protein kinase C activation by phorbol-12-myristate-13-acetate induces neural progenitor cell proliferation in vitro. We also show that the nontumorogenic protein kinase C activator prostratin exerts a proliferative effect on neural progenitor cells in vitro. This effect can be reverted by addition of the protein kinase C inhibitor G06850, demonstrating that the effect of prostratin is mediated by protein kinase C activation. Additionally, we show that prostratin treatment in vivo induces proliferation of neural progenitor cells within the dentate gyrus of the hippocampus and the subventricular zone. Finally, we describe a library of diterpenes with a 12-deoxyphorbol structure similar to that of prostratin that induces a stronger effect than prostratin on neural progenitor cell proliferation both in vitro and in vivo. Conclusions: This work suggests that protein kinase C activation is a promising strategy to expand the endogenous neural progenitor cell population to promote neurogenesis and highlights the potential of 12-deoxyphorbols as pharmaceutical

  19. Mapping neural circuits with activity-dependent nuclear import of a transcription factor.

    PubMed

    Masuyama, Kaoru; Zhang, Yi; Rao, Yi; Wang, Jing W

    2012-03-01

    Abstract: Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method-CaLexA (calcium-dependent nuclear import of LexA)-for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals. PMID:22236090

  20. Immune Challenge Activates Neural Inputs to the Ventrolateral Bed Nucleus of the Stria Terminalis

    PubMed Central

    Bienkowski, Michael S.; Rinaman, Linda

    2011-01-01

    Hypothalamo-pituitary-adrenal (HPA) axis activation in response to infection is an important mechanism by which the nervous system can suppress inflammation. HPA output is controlled by the hypothalamic paraventricular nucleus (PVN). Previously, we determined that noradrenergic inputs to the PVN contribute to, but do not entirely account for, the ability of bacterial endotoxin (i.e., lipopolysacharide, LPS) to activate the HPA axis. The present study investigated LPS-induced recruitment of neural inputs to the ventrolateral bed nucleus of the stria terminalis (vlBNST). GABAergic projections from the vlBNST inhibit PVN neurons at the apex of the HPA axis; thus, we hypothesize that LPS treatment activates inhibitory inputs to the vlBNST to thereby “disinhibit” the PVN and increase HPA output. To test this hypothesis, retrograde neural tracer was iontophoretically delivered into the vlBNST of adult male rats to retrogradely label central sources of axonal input. After one week, rats were injected i.p. with either LPS (200 µg/kg BW) or saline vehicle, and then perfused with fixative 2.5 hours later. Brains were processed for immunohistochemical localization of retrograde tracer and the immediate-early gene product, Fos (a marker of neural activation). Brain regions that provide inhibitory input to the vlBNST (e.g., caudal nucleus of the solitary tract, central amygdala, dorsolateral BNST) were preferentially activated by LPS, whereas sources of excitatory input (e.g., paraventricular thalamus, medial prefrontal cortex) were not activated or were activated less robustly. These results suggest that LPS treatment recruits central neural systems that actively suppress vlBNST neural activity, thereby removing a potent source of inhibitory control over the HPA axis. PMID:21402087

  1. Improved training of neural networks for the nonlinear active control of sound and vibration.

    PubMed

    Bouchard, M; Paillard, B; Le Dinh, C T

    1999-01-01

    Active control of sound and vibration has been the subject of a lot of research in recent years, and examples of applications are now numerous. However, few practical implementations of nonlinear active controllers have been realized. Nonlinear active controllers may be required in cases where the actuators used in active control systems exhibit nonlinear characteristics, or in cases when the structure to be controlled exhibits a nonlinear behavior. A multilayer perceptron neural-network based control structure was previously introduced as a nonlinear active controller, with a training algorithm based on an extended backpropagation scheme. This paper introduces new heuristical training algorithms for the same neural-network control structure. The objective is to develop new algorithms with faster convergence speed (by using nonlinear recursive-least-squares algorithms) and/or lower computational loads (by using an alternative approach to compute the instantaneous gradient of the cost function). Experimental results of active sound control using a nonlinear actuator with linear and nonlinear controllers are presented. The results show that some of the new algorithms can greatly improve the learning rate of the neural-network control structure, and that for the considered experimental setup a neural-network controller can outperform linear controllers. PMID:18252535

  2. Aberrant hippocampal Atp8a1 levels are associated with altered synaptic strength, electrical activity, and autistic-like behavior.

    PubMed

    Kerr, Daniel J; Marsillo, Alexandra; Guariglia, Sara R; Budylin, Tatyana; Sadek, Rodina; Menkes, Silvia; Chauhan, Abha; Wen, Guang Y; McCloskey, Daniel P; Wieraszko, Andrzej; Banerjee, Probal

    2016-09-01

    Type IV ATPases are putative aminophospholipid translocases (APLTs), more commonly known as flippases. A pronounced induction of the flippase Atp8a1 was observed in post-mortem tissue homogenates from the hippocampus and temporal lobe of juvenile autistic subjects compared to age-matched controls. In order to simulate the human data, C57BL/6 mice were allowed to develop after intra-hippocampal injection of recombinant lentivirus expressing Atp8a1 at the early developmental stage of postnatal day 6 (P6). Transmission electron microscopy (TEM) analysis of the lentivirus-Atp8a1 treated (Atp8a1+) mice in adulthood revealed fewer and weaker excitatory synapses in the hippocampal CA1 region compared to mice injected with empty virus. Significant inhibition of the Schaffer collateral pathway was observed in the Atp8a1+ mice in paired-pulse recording (PPR) at 20-ms inter-stimulus interval. In the three-chambered sociability test, the Atp8a1+ mice displayed no preference for an encaged stranger mouse over a novel object, which is a characteristic autistic-like behavior. In sharp contrast, Atp8a1 (-/-) mice displayed a preference for a stranger mouse over the novel object, which is characteristic of neurotypical mouse behavior. However, similar to the Atp8a1+ mice, the Atp8a1 (-/-) mice harbored fewer and weaker excitatory synapses in CA1 compared to wild-type controls, and displayed inhibition at 20-ms inter-stimulus interval in PPR. These findings suggest that both elevated and diminished levels of Atp8a1 during early development are detrimental to brain connectivity, but only elevated Atp8a1 is associated with aberrant social behavior. Mice with augmented levels of Atp8a1 may therefore serve as a potential model in autism research. PMID:27287255

  3. Application of neural networks with orthogonal activation functions in control of dynamical systems

    NASA Astrophysics Data System (ADS)

    Nikolić, Saša S.; Antić, Dragan S.; Milojković, Marko T.; Milovanović, Miroslav B.; Perić, Staniša Lj.; Mitić, Darko B.

    2016-04-01

    In this article, we present a new method for the synthesis of almost and quasi-orthogonal polynomials of arbitrary order. Filters designed on the bases of these functions are generators of generalised quasi-orthogonal signals for which we derived and presented necessary mathematical background. Based on theoretical results, we designed and practically implemented generalised first-order (k = 1) quasi-orthogonal filter and proved its quasi-orthogonality via performed experiments. Designed filters can be applied in many scientific areas. In this article, generated functions were successfully implemented in Nonlinear Auto Regressive eXogenous (NARX) neural network as activation functions. One practical application of the designed orthogonal neural network is demonstrated through the example of control of the complex technical non-linear system - laboratory magnetic levitation system. Obtained results were compared with neural networks with standard activation functions and orthogonal functions of trigonometric shape. The proposed network demonstrated superiority over existing solutions in the sense of system performances.

  4. Optogenetic Perturbation of Neural Activity with Laser Illumination in Semi-intact Drosophila Larvae in Motion

    PubMed Central

    Matsunaga, Teruyuki; Fushiki, Akira; Nose, Akinao; Kohsaka, Hiroshi

    2013-01-01

    Drosophila larval locomotion is a splendid model system in developmental and physiological neuroscience, by virtue of the genetic accessibility of the underlying neuronal components in the circuits1-6. Application of optogenetics7,8 in the larval neural circuit allows us to manipulate neuronal activity in spatially and temporally patterned ways9-13. Typically, specimens are broadly illuminated with a mercury lamp or LED, so specificity of the target neurons is controlled by binary gene expression systems such as the Gal4-UAS system14,15. In this work, to improve the spatial resolution to "sub-genetic resolution", we locally illuminated a subset of neurons in the ventral nerve cord using lasers implemented in a conventional confocal microscope. While monitoring the motion of the body wall of the semi-intact larvae, we interactively activated or inhibited neural activity with channelrhodopsin16,17 or halorhodopsin18-20, respectively. By spatially and temporally restricted illumination of the neural tissue, we can manipulate the activity of specific neurons in the circuit at a specific phase of behavior. This method is useful for studying the relationship between the activities of a local neural assembly in the ventral nerve cord and the spatiotemporal pattern of motor output. PMID:23851598

  5. Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol.

    PubMed

    Patel, Reesha R; Barbosa, Cindy; Brustovetsky, Tatiana; Brustovetsky, Nickolay; Cummins, Theodore R

    2016-08-01

    Mutations in brain isoforms of voltage-gated sodium channels have been identified in patients with distinct epileptic phenotypes. Clinically, these patients often do not respond well to classic anti-epileptics and many remain refractory to treatment. Exogenous as well as endogenous cannabinoids have been shown to target voltage-gated sodium channels and cannabidiol has recently received attention for its potential efficacy in the treatment of childhood epilepsies. In this study, we further investigated the ability of cannabinoids to modulate sodium currents from wild-type and epilepsy-associated mutant voltage-gated sodium channels. We first determined the biophysical consequences of epilepsy-associated missense mutations in both Nav1.1 (arginine 1648 to histidine and asparagine 1788 to lysine) and Nav1.6 (asparagine 1768 to aspartic acid and leucine 1331 to valine) by obtaining whole-cell patch clamp recordings in human embryonic kidney 293T cells with 200 μM Navβ4 peptide in the pipette solution to induce resurgent sodium currents. Resurgent sodium current is an atypical near threshold current predicted to increase neuronal excitability and has been implicated in multiple disorders of excitability. We found that both mutations in Nav1.6 dramatically increased resurgent currents while mutations in Nav1.1 did not. We then examined the effects of anandamide and cannabidiol on peak transient and resurgent currents from wild-type and mutant channels. Interestingly, we found that cannabidiol can preferentially target resurgent sodium currents over peak transient currents generated by wild-type Nav1.6 as well as the aberrant resurgent and persistent current generated by Nav1.6 mutant channels. To further validate our findings, we examined the effects of cannabidiol on endogenous sodium currents from striatal neurons, and similarly we found an inhibition of resurgent and persistent current by cannabidiol. Moreover, current clamp recordings show that cannabidiol reduces

  6. Using near-infrared spectroscopy to assess neural activation during object processing in infants.

    PubMed

    Wilcox, Teresa; Bortfeld, Heather; Woods, Rebecca; Wruck, Eric; Boas, David A

    2005-01-01

    The capacity to represent the world in terms of numerically distinct objects (i.e., object individuation) is a milestone in early cognitive development and forms the foundation for more complex thought and behavior. Over the past 10 to 15 yr, infant researchers have expended a great deal of effort to identify the origins and development of this capacity. In contrast, relatively little is known about the neural mechanisms that underlie the ability to individuate objects, in large part because there are a limited number of noninvasive techniques available to measure brain functioning in human infants. Recent research suggests that near-IR spectroscopy (NIRS), an optical imaging technique that uses relative changes in total hemoglobin concentration and oxygenation as an indicator of neural activation, may be a viable procedure for assessing the relation between object processing and brain function in human infants. We examine the extent to which increased neural activation, as measured by NIRS, could be observed in two neural areas known to be involved in object processing, the primary visual cortex and the inferior temporal cortex, during an object processing task. Infants aged 6.5 months are presented with a visual event in which two featurally distinct objects emerge successively to opposite sides of an occluder and neuroimaging data are collected. As predicted, increased neural activation is observed in both the primary visual and inferior cortex during the visual event, suggesting that these neural areas support object processing in the young infant. The outcome has important implications for research in cognitive development, developmental neuroscience, and optical imaging. PMID:15847576

  7. Electrical and Optical Activation of Mesoscale Neural Circuits with Implications for Coding

    PubMed Central

    Millard, Daniel C.; Whitmire, Clarissa J.; Gollnick, Clare A.; Rozell, Christopher J.

    2015-01-01

    Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery of circuit function and for engineered approaches to alleviate various disorders of the nervous system. However, evidence suggests that neural activity generated by artificial stimuli differs dramatically from normal circuit function, in terms of both the local neuronal population activity at the site of activation and the propagation to downstream brain structures. The precise nature of these differences and the implications for information processing remain unknown. Here, we used voltage-sensitive dye imaging of primary somatosensory cortex in the anesthetized rat in response to deflections of the facial vibrissae and electrical or optogenetic stimulation of thalamic neurons that project directly to the somatosensory cortex. Although the different inputs produced responses that were similar in terms of the average cortical activation, the variability of the cortical response was strikingly different for artificial versus sensory inputs. Furthermore, electrical microstimulation resulted in highly unnatural spatial activation of cortex, whereas optical input resulted in spatial cortical activation that was similar to that induced by sensory inputs. A thalamocortical network model suggested that observed differences could be explained by differences in the way in which artificial and natural inputs modulate the magnitude and synchrony of population activity. Finally, the variability structure in the response for each case strongly influenced the optimal inputs for driving the pathway from the perspective of an ideal observer of cortical activation when considered in the context of information transmission. SIGNIFICANCE STATEMENT Artificial activation of neural circuitry through electrical microstimulation and optogenetic techniques is important for both scientific discovery and clinical translation. However, neural

  8. Aggression- and sex-induced neural activity across vasotocin populations in the brown anole.

    PubMed

    Kabelik, David; Alix, Veronica C; Burford, Emily R; Singh, Leah J

    2013-03-01

    Activity within the social behavior neural network is modulated by the neuropeptide arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP). However, central AVT/AVP release causes different behavioral effects across species and social environments. These differences may be due to the activation of different neuronal AVT/AVP populations or to similar activity patterns causing different behavioral outputs. We examined neural activity (assessed as Fos induction) within AVT neurons in male brown anole lizards (Anolis sagrei) participating in aggressive or sexual encounters. Lizards possess simple amniote nervous systems, and their examination provides a comparative framework to complement avian and mammalian studies. In accordance with findings in other species, AVT neurons in the anole paraventricular nucleus (PVN) were activated during aggressive encounters; but unlike in other species, a positive correlation was found between aggression levels and activation. Activation of AVT neurons within the supraoptic nucleus (SON) occurred nonspecifically with participation in either aggressive or sexual encounters. Activation of AVT neurons in the preoptic area (POA) and bed nucleus of the stria terminalis (BNST) was associated with engagement in sexual behaviors. The above findings are congruent with neural activation patterns observed in other species, even when the behavioral outputs (i.e., aggression level) differed. However, aggressive encounters also increased activation of AVT neurons in the BNST, which is incongruous with findings in other species. Thus, some species differences involve the encoding of social stimuli as different neural activation patterns within the AVT/AVP network, whereas other behavioral differences arise downstream of this system. PMID:23201179

  9. Using Perfusion fMRI to Measure Continuous Changes in Neural Activity with Learning

    ERIC Educational Resources Information Center

    Olson, Ingrid R.; Rao, Hengyi; Moore, Katherine Sledge; Wang, Jiongjiong; Detre, John A.; Aguirre, Geoffrey K.

    2006-01-01

    In this study, we examine the suitability of a relatively new imaging technique, "arterial spin labeled perfusion imaging," for the study of continuous, gradual changes in neural activity. Unlike BOLD imaging, the perfusion signal is stable over long time-scales, allowing for accurate assessment of continuous performance. In addition, perfusion…

  10. Differences in Feedback- and Inhibition-Related Neural Activity in Adult ADHD

    ERIC Educational Resources Information Center

    Dibbets, Pauline; Evers, Lisbeth; Hurks, Petra; Marchetta, Natalie; Jolles, Jelle

    2009-01-01

    The objective of this study was to examine response inhibition- and feedback-related neural activity in adults with attention deficit hyperactivity disorder (ADHD) using event-related functional MRI. Sixteen male adults with ADHD and 13 healthy/normal controls participated in this study and performed a modified Go/NoGo task. Behaviourally,…

  11. Specific and Nonspecific Neural Activity during Selective Processing of Visual Representations in Working Memory

    ERIC Educational Resources Information Center

    Oh, Hwamee; Leung, Hoi-Chung

    2010-01-01

    In this fMRI study, we investigated prefrontal cortex (PFC) and visual association regions during selective information processing. We recorded behavioral responses and neural activity during a delayed recognition task with a cue presented during the delay period. A specific cue ("Face" or "Scene") was used to indicate which one of the two…

  12. Differential neural activity patterns for spatial relations in humans: a MEG study.

    PubMed

    Scott, Nicole M; Leuthold, Arthur; Sera, Maria D; Georgopoulos, Apostolos P

    2016-02-01

    Children learn the words for above-below relations earlier than for left-right relations, despite treating these equally well in a simple visual categorization task. Even as adults--conflicts in congruency, such as when a stimulus is depicted in a spatially incongruent manner with respect to salient global cues--can be challenging. Here we investigated the neural correlates of encoding and maintaining in working memory above-below and left-right relational planes in 12 adults using magnetoencephalography in order to discover whether above-below relations are represented by the brain differently than left-right relations. Adults performed perfectly on the task behaviorally, so any differences in neural activity were attributed to the stimuli's cognitive attributes. In comparing above-below to left-right relations during stimulus encoding, we found the greatest differences in neural activity in areas associated with space and movement. In comparing congruent to incongruent trials, we found the greatest differential activity in premotor areas. For both contrasts, brain areas involved in the encoding phase were also involved in the maintenance phase, which provides evidence that those brain areas are particularly important in representing the relational planes or congruency types throughout the trial. When comparing neural activity associated with the relational planes during working memory, additional right posterior areas were implicated, whereas the congruent-incongruent contrast implicated additional bilateral frontal and temporal areas. These findings are consistent with the hypothesis left-right relations are represented differently than above-below relations. PMID:26514809

  13. Global robust dissipativity of interval recurrent neural networks with time-varying delay and discontinuous activations.

    PubMed

    Duan, Lian; Huang, Lihong; Guo, Zhenyuan

    2016-07-01

    In this paper, the problems of robust dissipativity and robust exponential dissipativity are discussed for a class of recurrent neural networks with time-varying delay and discontinuous activations. We extend an invariance principle for the study of the dissipativity problem of delay systems to the discontinuous case. Based on the developed theory, some novel criteria for checking the global robust dissipativity and global robust exponential dissipativity of the addressed neural network model are established by constructing appropriate Lyapunov functionals and employing the theory of Filippov systems and matrix inequality techniques. The effectiveness of the theoretical results is shown by two examples with numerical simulations. PMID:27475061

  14. Global robust dissipativity of interval recurrent neural networks with time-varying delay and discontinuous activations

    NASA Astrophysics Data System (ADS)

    Duan, Lian; Huang, Lihong; Guo, Zhenyuan

    2016-07-01

    In this paper, the problems of robust dissipativity and robust exponential dissipativity are discussed for a class of recurrent neural networks with time-varying delay and discontinuous activations. We extend an invariance principle for the study of the dissipativity problem of delay systems to the discontinuous case. Based on the developed theory, some novel criteria for checking the global robust dissipativity and global robust exponential dissipativity of the addressed neural network model are established by constructing appropriate Lyapunov functionals and employing the theory of Filippov systems and matrix inequality techniques. The effectiveness of the theoretical results is shown by two examples with numerical simulations.

  15. Techniques for extracting single-trial activity patterns from large-scale neural recordings.

    PubMed

    Churchland, Mark M; Yu, Byron M; Sahani, Maneesh; Shenoy, Krishna V

    2007-10-01

    Large, chronically implanted arrays of microelectrodes are an increasingly common tool for recording from primate cortex and can provide extracellular recordings from many (order of 100) neurons. While the desire for cortically based motor prostheses has helped drive their development, such arrays also offer great potential to advance basic neuroscience research. Here we discuss the utility of array recording for the study of neural dynamics. Neural activity often has dynamics beyond that driven directly by the stimulus. While governed by those dynamics, neural responses may nevertheless unfold differently for nominally identical trials, rendering many traditional analysis methods ineffective. We review recent studies - some employing simultaneous recording, some not - indicating that such variability is indeed present both during movement generation and during the preceding premotor computations. In such cases, large-scale simultaneous recordings have the potential to provide an unprecedented view of neural dynamics at the level of single trials. However, this enterprise will depend not only on techniques for simultaneous recording but also on the use and further development of analysis techniques that can appropriately reduce the dimensionality of the data, and allow visualization of single-trial neural behavior. PMID:18093826

  16. Chromatin Remodeling Inactivates Activity Genes and Regulates Neural Coding

    PubMed Central

    Hill, Kelly K.; Hemberg, Martin; Reddy, Naveen C.; Cho, Ha Y.; Guthrie, Arden N.; Oldenborg, Anna; Heiney, Shane A.; Ohmae, Shogo; Medina, Javier F.; Holy, Timothy E.; Bonni, Azad

    2016-01-01

    Activity-dependent transcription influences neuronal connectivity, but the roles and mechanisms of inactivation of activity-dependent genes have remained poorly understood. Genome-wide analyses in the mouse cerebellum revealed that the nucleosome remodeling and deacetylase (NuRD) complex deposits the histone variant H2A.z at promoters of activity-dependent genes, thereby triggering their inactivation. Purification of translating mRNAs from synchronously developing granule neurons (Sync-TRAP) showed that conditional knockout of the core NuRD subunit Chd4 impairs inactivation of activity-dependent genes when neurons undergo dendrite pruning. Chd4 knockout or expression of NuRD-regulated activity genes impairs dendrite pruning. Imaging of behaving mice revealed hyperresponsivity of granule neurons to sensorimotor stimuli upon Chd4 knockout. Our findings define an epigenetic mechanism that inactivates activity-dependent transcription and regulates dendrite patterning and sensorimotor encoding in the brain. PMID:27418512

  17. Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches.

    PubMed

    Ma, Ying; Shaik, Mohammed A; Kim, Sharon H; Kozberg, Mariel G; Thibodeaux, David N; Zhao, Hanzhi T; Yu, Hang; Hillman, Elizabeth M C

    2016-10-01

    Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574312

  18. Hierarchical Interaction Structure of Neural Activities in Cortical Slice Cultures

    PubMed Central

    Santos, Gustavo S.; Gireesh, Elakkat D.; Plenz, Dietmar; Nakahara, Hiroyuki

    2010-01-01

    Recent advances in the analysis of neuronal activities suggest that the instantaneous activity patterns can be mostly explained by considering only first-order and pairwise interactions between recorded elements, i.e., action potentials or local field potentials (LFP), and do not require higher-than-pairwise-order interactions. If generally applicable, this pairwise approach greatly simplifies the description of network interactions. However, an important question remains: are the recorded elements the units of interaction that best describe neuronal activity patterns? To explore this, we recorded spontaneous LFP peak activities in cortical organotypic cultures using planar, integrated 60-microelectrode arrays. We compared predictions obtained using a pairwise approach with those using a hierarchical approach that uses two different spatial units for describing the activity interactions: single electrodes and electrode clusters. In this hierarchical model, short-range interactions within each cluster were modeled by pairwise interactions of electrode activities and long-range interactions were modeled by pairwise interactions of cluster activities. Despite the relatively low number of parameters used, the hierarchical model provided a more accurate description of the activity patterns than the pairwise model when applied to ensembles of 10 electrodes. Furthermore, the hierarchical model was successfully applied to a larger-scale data of ~60 electrodes. Electrode activities within clusters were highly correlated and spatially contiguous. In contrast, long-range interactions were diffuse, suggesting the presence of higher-than-pairwise-order interactions involved in the LFP peak activities. Thus, the identification of appropriate units of interaction may allow for the successful characterization of neuronal activities in large-scale networks. PMID:20592194

  19. Neural activity promotes long-distance, target-specific regeneration of adult retinal axons.

    PubMed

    Lim, Jung-Hwan A; Stafford, Benjamin K; Nguyen, Phong L; Lien, Brian V; Wang, Chen; Zukor, Katherine; He, Zhigang; Huberman, Andrew D

    2016-08-01

    Axons in the mammalian CNS fail to regenerate after injury. Here we show that if the activity of mouse retinal ganglion cells (RGCs) is increased by visual stimulation or using chemogenetics, their axons regenerate. We also show that if enhancement of neural activity is combined with elevation of the cell-growth-promoting pathway involving mammalian target of rapamycin (mTOR), RGC axons regenerate long distances and re-innervate the brain. Analysis of genetically labeled RGCs revealed that this regrowth can be target specific: RGC axons navigated back to their correct visual targets and avoided targets incorrect for their function. Moreover, these regenerated connections were successful in partially rescuing a subset of visual behaviors. Our findings indicate that combining neural activity with activation of mTOR can serve as powerful tool for enhancing axon regeneration, and they highlight the remarkable capacity of CNS neurons to re-establish accurate circuit connections in adulthood. PMID:27399843

  20. Correlates of reward-predictive value in learning-related hippocampal neural activity

    PubMed Central

    Okatan, Murat

    2009-01-01

    Temporal difference learning (TD) is a popular algorithm in machine learning. Two learning signals that are derived from this algorithm, the predictive value and the prediction error, have been shown to explain changes in neural activity and behavior during learning across species. Here, the predictive value signal is used to explain the time course of learning-related changes in the activity of hippocampal neurons in monkeys performing an associative learning task. The TD algorithm serves as the centerpiece of a joint probability model for the learning-related neural activity and the behavioral responses recorded during the task. The neural component of the model consists of spiking neurons that compete and learn the reward-predictive value of task-relevant input signals. The predictive-value signaled by these neurons influences the behavioral response generated by a stochastic decision stage, which constitutes the behavioral component of the model. It is shown that the time course of the changes in neural activity and behavioral performance generated by the model exhibits key features of the experimental data. The results suggest that information about correct associations may be expressed in the hippocampus before it is detected in the behavior of a subject. In this way, the hippocampus may be among the earliest brain areas to express learning and drive the behavioral changes associated with learning. Correlates of reward-predictive value may be expressed in the hippocampus through rate remapping within spatial memory representations, they may represent reward-related aspects of a declarative or explicit relational memory representation of task contingencies, or they may correspond to reward-related components of episodic memory representations. These potential functions are discussed in connection with hippocampal cell assembly sequences and their reverse reactivation during the awake state. The results provide further support for the proposal that neural

  1. Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.

    PubMed

    Huang, Zirui; Wang, Zhiyao; Zhang, Jianfeng; Dai, Rui; Wu, Jinsong; Li, Yuan; Liang, Weimin; Mao, Ying; Yang, Zhong; Holland, Giles; Zhang, Jun; Northoff, Georg

    2014-11-01

    Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. PMID:24867379

  2. Early capillary flux homogenization in response to neural activation.

    PubMed

    Lee, Jonghwan; Wu, Weicheng; Boas, David A

    2016-02-01

    This Brief Communication reports early homogenization of capillary network flow during somatosensory activation in the rat cerebral cortex. We used optical coherence tomography and statistical intensity variation analysis for tracing changes in the red blood cell flux over hundreds of capillaries nearly at the same time with 1-s resolution. We observed that while the mean capillary flux exhibited a typical increase during activation, the standard deviation of the capillary flux exhibited an early decrease that happened before the mean flux increase. This network-level data is consistent with the theoretical hypothesis that capillary flow homogenizes during activation to improve oxygen delivery. PMID:26661145

  3. TLR9 signalling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus.

    PubMed

    Matsuda, Taito; Murao, Naoya; Katano, Yuki; Juliandi, Berry; Kohyama, Jun; Akira, Shizuo; Kawai, Taro; Nakashima, Kinichi

    2015-01-01

    Pathological conditions such as epilepsy cause misregulation of adult neural stem/progenitor populations in the adult hippocampus in mice, and the resulting abnormal neurogenesis leads to impairment in learning and memory. However, how animals cope with abnormal neurogenesis remains unknown. Here we show that microglia in the mouse hippocampus attenuate convulsive seizure-mediated aberrant neurogenesis through the activation of Toll-like receptor 9 (TLR9), an innate immune sensor known to recognize microbial DNA and trigger inflammatory responses. We found that microglia sense self-DNA from degenerating neurons following seizure, and secrete tumour necrosis factor-α, resulting in attenuation of aberrant neurogenesis. Furthermore, TLR9 deficiency exacerbated seizure-induced cognitive decline and recurrent seizure severity. Our findings thus suggest the existence of bidirectional communication between the innate immune and nervous systems for the maintenance of adult brain integrity. PMID:25751136

  4. Ligand-Independent Canonical Wnt Activity in Canine Mammary Tumor Cell Lines Associated with Aberrant LEF1 Expression

    PubMed Central

    van Wolferen, Monique E.; Rao, Nagesha A. S.; Grizelj, Juraj; Vince, Silvijo; Hellmen, Eva; Mol, Jan A.

    2014-01-01

    Pet dogs very frequently develop spontaneous mammary tumors and have been suggested as a good model organism for breast cancer research. In order to obtain an insight into underlying signaling mechanisms during canine mammary tumorigenesis, in this study we assessed the incidence and the mechanism of canonical Wnt activation in a panel of 12 canine mammary tumor cell lines. We show that a subset of canine mammary cell lines exhibit a moderate canonical Wnt activity that is dependent on Wnt ligands, similar to what has been described in human breast cancer cell lines. In addition, three of the tested canine mammary cell lines have a high canonical Wnt activity that is not responsive to inhibitors of Wnt ligand secretion. Tumor cell lines with highly active canonical Wnt signaling often carry mutations in key members of the Wnt signaling cascade. These cell lines, however, carry no mutations in the coding regions of intracellular Wnt pathway components (APC, β-catenin, GSK3β, CK1α and Axin1) and have a functional β-catenin destruction complex. Interestingly, however, the cell lines with high canonical Wnt activity specifically overexpress LEF1 mRNA and the knock-down of LEF1 significantly inhibits TCF-reporter activity. In addition, LEF1 is overexpressed in a subset of canine mammary carcinomas, implicating LEF1 in ligand-independent activation of canonical Wnt signaling in canine mammary tumors. We conclude that canonical Wnt activation may be a frequent event in canine mammary tumors both through Wnt ligand-dependent and novel ligand–independent mechanisms. PMID:24887235

  5. Neural portraits of perception: reconstructing face images from evoked brain activity.

    PubMed

    Cowen, Alan S; Chun, Marvin M; Kuhl, Brice A

    2014-07-01

    Recent neuroimaging advances have allowed visual experience to be reconstructed from patterns of brain activity. While neural reconstructions have ranged in complexity, they have relied almost exclusively on retinotopic mappings between visual input and activity in early visual cortex. However, subjective perceptual information is tied more closely to higher-level cortical regions that have not yet been used as the primary basis for neural reconstructions. Furthermore, no reconstruction studies to date have reported reconstructions of face images, which activate a highly distributed cortical network. Thus, we investigated (a) whether individual face images could be accurately reconstructed from distributed patterns of neural activity, and (b) whether this could be achieved even when excluding activity within occipital cortex. Our approach involved four steps. (1) Principal component analysis (PCA) was used to identify components that efficiently represented a set of training faces. (2) The identified components were then mapped, using a machine learning algorithm, to fMRI activity collected during viewing of the training faces. (3) Based on activity elicited by a new set of test faces, the algorithm predicted associated component scores. (4) Finally, these scores were transformed into reconstructed images. Using both objective and subjective validation measures, we show that our methods yield strikingly accurate neural reconstructions of faces even when excluding occipital cortex. This methodology not only represents a novel and promising approach for investigating face perception, but also suggests avenues for reconstructing 'offline' visual experiences-including dreams, memories, and imagination-which are chiefly represented in higher-level cortical areas. PMID:24650597

  6. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

    PubMed Central

    Hermans, Erno J.; Keysers, Christian; van Honk, Jack

    2015-01-01

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have repeatedly been shown to improve cognitive empathy (e.g. mind reading and emotion recognition). However, OXT has not yet been shown to increase neural empathic responses to pain in others, a core aspect of affective empathy. Effects of OXT on empathy for pain are difficult to predict, because OXT evidently has pain-reducing properties. Accordingly, OXT might paradoxically decrease empathy for pain. Here, using functional neuroimaging we show robust activation in the neural circuitry of pain (insula and sensorimotor regions) when subjects observe pain in others. Crucially, this empathy-related activation in the neural circuitry of pain is strongly reduced after intranasal OXT, specifically in the left insula. OXT on the basis of our neuroimaging data thus remarkably decreases empathy for pain, but further research including behavioral measures are necessary to draw definite conclusions. PMID:25818690

  7. Oxytocin reduces neural activity in the pain circuitry when seeing pain in others.

    PubMed

    Bos, Peter A; Montoya, Estrella R; Hermans, Erno J; Keysers, Christian; van Honk, Jack

    2015-06-01

    Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have repeatedly been shown to improve cognitive empathy (e.g. mind reading and emotion recognition). However, OXT has not yet been shown to increase neural empathic responses to pain in others, a core aspect of affective empathy. Effects of OXT on empathy for pain are difficult to predict, because OXT evidently has pain-reducing properties. Accordingly, OXT might paradoxically decrease empathy for pain. Here, using functional neuroimaging we show robust activation in the neural circuitry of pain (insula and sensorimotor regions) when subjects observe pain in others. Crucially, this empathy-related activation in the neural circuitry of pain is strongly reduced after intranasal OXT, specifically in the left insula. OXT on the basis of our neuroimaging data thus remarkably decreases empathy for pain, but further research including behavioral measures is necessary to draw definite conclusions. PMID:25818690

  8. Notch Activity Modulates the Responsiveness of Neural Progenitors to Sonic Hedgehog Signaling

    PubMed Central

    Kong, Jennifer H.; Yang, Linlin; Dessaud, Eric; Chuang, Katherine; Moore, Destaye M.; Rohatgi, Rajat; Briscoe, James; Novitch, Bennett G.

    2015-01-01

    Summary Throughout the developing nervous system, neural stem and progenitor cells give rise to diverse classes of neurons and glia in a spatially and temporally coordinated manner. In the ventral spinal cord, much of this diversity emerges through the morphogen actions of Sonic hedgehog (Shh). Interpretation of the Shh gradient depends on both the amount of ligand and duration of exposure, but the mechanisms permitting prolonged responses to Shh are not well understood. We demonstrate that Notch signaling plays an essential role in this process, enabling neural progenitors to attain sufficiently high levels of Shh pathway activity needed to direct the ventral-most cell fates. Notch activity regulates subcellular localization of the Shh receptor Patched1, gating the translocation of the key effector Smoothened to primary cilia and its downstream signaling activities. These data reveal an unexpected role for Notch shaping the interpretation of the Shh morphogen gradient and influencing cell fate determination. PMID:25936505

  9. Optical coherence tomography for cross-sectional imaging of neural activity

    PubMed Central

    Yeh, Yi-Jou; Black, Adam J.; Landowne, David; Akkin, Taner

    2015-01-01

    Abstract. We report a functional optical coherence tomography cross-sectional scanner to detect neural activity using unmyelinated nerves dissected from squid. The nerves, unstained or stained with a voltage-sensitive dye, were imaged in a nerve chamber. Transient phase changes from backscattered light were detected during action potential propagation. The results show that the scanner can provide high spatiotemporal resolution cross-sectional images of neural activity (15  μs/A-line; 0.25  ms/B-scan; ∼8.5×5.5  μm2 in xz). The advantage of this method compared to monitoring a single depth profile z is a dramatic increase in the number of available sites that can be measured in two spatial dimensions xz with lateral scanning; therefore, the study demonstrates that two-dimensional monitoring of small-scale functional activity would also be feasible. PMID:26217674

  10. Investigating the correlation between the neural activity and task performance in a psychomotor vigilance test.

    PubMed

    Hu, Zhongze; Sun, Yu; Lim, Julian; Thakor, Nitish; Bezerianos, Anastasios

    2015-01-01

    Neural activity is known to correlate with decrements in task performance as individuals enter the state of mental fatigue which might lead to lowered productivity and increased safety risks. Incorporating a passive brain computer interface (BCI) technique that detects changes in subject's neural activity and predicts the behavioral performance when the subject is underperforming might be a promising approach to reduce human error in real-world situations. Here, we developed a reliable model using EEG power spectrum to estimate time-on-task performance in a psychomotor vigilance test (PVT) which can fit across individuals. High correlation between the estimated and actual reaction time was achieved. Hence, our results illustrate the feasibility for modeling time-on-task decrements in performance among different individuals from their brainwave activity, with potential applications in several domains, including traffic and industrial safety. PMID:26737349

  11. Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

    PubMed Central

    Varghese, Binny V.; Koohestani, Faezeh; McWilliams, Michelle; Colvin, Arlene; Gunewardena, Sumedha; Kinsey, William H.; Nowak, Romana A.; Nothnick, Warren B.; Chennathukuzhi, Vargheese M.

    2013-01-01

    Uterine fibroids (leiomyomas) are the most common tumors of the female reproductive tract, occurring in up to 77% of reproductive-aged women, yet molecular pathogenesis remains poorly understood. A role for atypically activated mammalian target of rapamycin (mTOR) pathway in the pathogenesis of uterine fibroids has been suggested in several studies. We identified that G protein-coupled receptor 10 [GPR10, a putative signaling protein upstream of the phosphoinositide 3-kinase–protein kinase B/AKT–mammalian target of rapamycin (PI3K/AKT–mTOR) pathway] is aberrantly expressed in uterine fibroids. The activation of GPR10 by its cognate ligand, prolactin releasing peptide, promotes PI3K–AKT–mTOR pathways and cell proliferation specifically in cultured primary leiomyoma cells. Additionally, we report that RE1 suppressing transcription factor/neuron-restrictive silencing factor (REST/NRSF), a known tumor suppressor, transcriptionally represses GPR10 in the normal myometrium, and that the loss of REST in fibroids permits GPR10 expression. Importantly, mice overexpressing human GPR10 in the myometrium develop myometrial hyperplasia with excessive extracellular matrix deposition, a hallmark of uterine fibroids. We demonstrate previously unrecognized roles for GPR10 and its upstream regulator REST in the pathogenesis of uterine fibroids. Importantly, we report a unique genetically modified mouse model for a gene that is misexpressed in uterine fibroids. PMID:23284171

  12. Linking neural activity and molecular oscillations in the SCN

    PubMed Central

    Colwell, Christopher S.

    2015-01-01

    Neurons in the suprachiasmatic nucleus (SCN) function as part of a central timing circuit that drives daily changes in our behaviour and underlying physiology. A hallmark feature of SCN neuronal populations is that they are mostly electrically silent during the night, start to fire action potentials near dawn and then continue to generate action potentials with a slow and steady pace all day long. Sets of currents are responsible for this daily rhythm, with the strongest evidence for persistent Na+ currents, L-type Ca2+ currents, hyperpolarization-activated currents (IH), large-conductance Ca2+ activated K+ (BK) currents and fast delayed rectifier (FDR) K+ currents. These rhythms in electrical activity are crucial for the function of the circadian timing system, including the expression of clock genes, and decline with ageing and disease. This article reviews our current understanding of the ionic and molecular mechanisms that drive the rhythmic firing patterns in the SCN. PMID:21886186

  13. Modulation of neural activity during object naming: effects of time and practice.

    PubMed

    van Turennout, Miranda; Bielamowicz, Lisa; Martin, Alex

    2003-04-01

    Repeated exposure to objects improves our ability to identify and name them, even after a long delay. Previous brain imaging studies have demonstrated that this experience-related facilitation of object naming is associated with neural changes in distinct brain regions. We used event-related functional magnetic resonance imaging (fMRI) to examine the modulation of neural activity in the object naming system as a function of experience and time. Pictures of common objects were presented repeatedly for naming at different time intervals (1 h, 6 h and 3 days) before scanning, or at 30 s intervals during scanning. The results revealed that as objects became more familiar with experience, activity in occipitotemporal and left inferior frontal regions decreased while activity in the left insula and basal ganglia increased. In posterior regions, reductions in activity as a result of multiple repetitions did not interact with time, whereas in left inferior frontal cortex larger decreases were observed when repetitions were spaced out over time. This differential modulation of activity in distinct brain regions provides support for the idea that long-lasting object priming is mediated by two neural mechanisms. The first mechanism may involve changes in object-specific representations in occipitotemporal cortices, the second may be a form of procedural learning involving a reorganization in brain circuitry that leads to more efficient name retrieval. PMID:12631567

  14. Increased cell proliferation and neural activity by physostigmine in the telencephalon of adult zebrafish.

    PubMed

    Lee, Yunkyoung; Lee, Bongkyu; Jeong, Sumin; Park, Ji-Won; Han, Inn-Oc; Lee, Chang-Joong

    2016-08-26

    Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU-labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200μM physostigmine, which was inhibited by pretreatment with 200μM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200μM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30min treatment with 200μM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200μM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20μM physostigmine. These results suggest that 200μM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish. PMID:27378362

  15. Implications of the Dependence of Neuronal Activity on Neural Network States for the Design of Brain-Machine Interfaces

    PubMed Central

    Panzeri, Stefano; Safaai, Houman; De Feo, Vito; Vato, Alessandro

    2016-01-01

    Brain-machine interfaces (BMIs) can improve the quality of life of patients with sensory and motor disabilities by both decoding motor intentions expressed by neural activity, and by encoding artificially sensed information into patterns of neural activity elicited by causal interventions on the neural tissue. Yet, current BMIs can exchange relatively small amounts of information with the brain. This problem has proved difficult to overcome by simply increasing the number of recording or stimulating electrodes, because trial-to-trial variability of neural activity partly arises from intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation, and so is shared among neurons. Here we review recent progress in characterizing the state dependence of neural responses, and in particular of how neural responses depend on endogenous slow fluctuations of network excitability. We then elaborate on how this knowledge may be used to increase the amount of information that BMIs exchange with brain. Knowledge of network state can be used to fine-tune the stimulation pattern that should reliably elicit a target neural response used to encode information in the brain, and to discount part of the trial-by-trial variability of neural responses, so that they can be decoded more accurately. PMID:27147955

  16. Dampened neural activity and abolition of epileptic-like activity in cortical slices by active ingredients of spices

    PubMed Central

    Pezzoli, Maurizio; Elhamdani, Abdeladim; Camacho, Susana; Meystre, Julie; González, Stephanie Michlig; le Coutre, Johannes; Markram, Henry

    2014-01-01

    Active ingredients of spices (AIS) modulate neural response in the peripheral nervous system, mainly through interaction with TRP channel/receptors. The present study explores how different AIS modulate neural response in layer 5 pyramidal neurons of S1 neocortex. The AIS tested are agonists of TRPV1/3, TRPM8 or TRPA1. Our results demonstrate that capsaicin, eugenol, menthol, icilin and cinnamaldehyde, but not AITC dampen the generation of APs in a voltage- and time-dependent manner. This effect was further tested for the TRPM8 ligands in the presence of a TRPM8 blocker (BCTC) and on TRPM8 KO mice. The observable effect was still present. Finally, the influence of the selected AIS was tested on in vitro gabazine-induced seizures. Results coincide with the above observations: except for cinnamaldehyde, the same AIS were able to reduce the number, duration of the AP bursts and increase the concentration of gabazine needed to elicit them. In conclusion, our data suggests that some of these AIS can modulate glutamatergic neurons in the brain through a TRP-independent pathway, regardless of whether the neurons are stimulated intracellularly or by hyperactive microcircuitry. PMID:25359561

  17. Quantitative meta-analysis of neural activity in posttraumatic stress disorder

    PubMed Central

    2012-01-01

    Background In recent years, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have played a significant role in elucidating the neural underpinnings of posttraumatic stress disorder (PTSD). However, a detailed understanding of the neural regions implicated in the disorder remains incomplete because of considerable variability in findings across studies. The aim of this meta-analysis was to identify consistent patterns of neural activity across neuroimaging study designs in PTSD to improve understanding of the neurocircuitry of PTSD. Methods We conducted a literature search for PET and fMRI studies of PTSD that were published before February 2011. The article search resulted in 79 functional neuroimaging PTSD studies. Data from 26 PTSD peer-reviewed neuroimaging articles reporting results from 342 adult patients and 342 adult controls were included. Peak activation coordinates from selected articles were used to generate activation likelihood estimate maps separately for symptom provocation and cognitive-emotional studies of PTSD. A separate meta-analysis examined the coupling between ventromedial prefrontal cortex and amygdala activity in patients. Results Results demonstrated that the regions most consistently hyperactivated in PTSD patients included mid- and dorsal anterior cingulate cortex, and when ROI studies were included, bilateral amygdala. By contrast, widespread hypoactivity was observed in PTSD including the ventromedial prefrontal cortex and the inferior frontal gyrus. Furthermore, decreased ventromedial prefrontal cortex activity was associated with increased amygdala activity. Conclusions These results provide evidence for a neurocircuitry model of PTSD that emphasizes alteration in neural networks important for salience detection and emotion regulation. PMID:22738125

  18. Neural control of glutamine synthetase activity in rat skeletal muscles.

    PubMed

    Feng, B; Konagaya, M; Konagaya, Y; Thomas, J W; Banner, C; Mill, J; Max, S R

    1990-05-01

    The mechanism of glutamine synthetase induction in rat skeletal muscle after denervation or limb immobilization was investigated. Adult male rats were subjected to midthigh section of the sciatic nerve. At 1, 2, and 5 h and 1, 2, and 7 days after denervation, rats were killed and denervated, and contralateral control soleus and plantaris muscles were excised, weighted, homogenized, and assayed for glutamine synthetase. Glutamine synthetase activity increased approximately twofold 1 h after denervation in both muscles. By 7 days postdenervation enzyme activity had increased to three times the control level in plantaris muscle and to four times the control level in soleus muscle. Increased enzyme activity after nerve section was associated with increased maximum velocity with no change in apparent Michaelis constant. Immunotitration with an antiglutamine synthetase antibody suggested that denervation caused an increase in the number of glutamine synthetase molecules in muscle. However, Northern-blot analysis revealed no increase in the steady-state level of glutamine synthetase mRNA after denervation. A mixing experiment failed to yield evidence for the presence of a soluble factor involved in regulating the activity of glutamine synthetase in denervated muscle. A combination of denervation and dexamethasone injections resulted in additive increases in glutamine synthetase. Thus the mechanism underlying increased glutamine synthetase after denervation appears to be posttranscriptional and is distinct from that of the glucocorticoid-mediated glutamine synthetase induction previously described by us. PMID:1970709

  19. Optimal Recognition Method of Human Activities Using Artificial Neural Networks

    NASA Astrophysics Data System (ADS)

    Oniga, Stefan; József, Sütő

    2015-12-01

    The aim of this research is an exhaustive analysis of the various factors that may influence the recognition rate of the human activity using wearable sensors data. We made a total of 1674 simulations on a publically released human activity database by a group of researcher from the University of California at Berkeley. In a previous research, we analyzed the influence of the number of sensors and their placement. In the present research we have examined the influence of the number of sensor nodes, the type of sensor node, preprocessing algorithms, type of classifier and its parameters. The final purpose is to find the optimal setup for best recognition rates with lowest hardware and software costs.

  20. Environmental layout complexity affects neural activity during navigation in humans.

    PubMed

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. PMID:26990572

  1. Placebo-Activated Neural Systems are Linked to Antidepressant Responses

    PubMed Central

    Peciña, Marta; Bohnert, Amy S. B.; Sikora, Magdalena; Avery, Erich T.; Langenecker, Scott A.; Mickey, Brian J.; Zubieta, Jon-Kar

    2016-01-01

    Importance High placebo responses have been observed across a wide range of pathologies, severely impacting drug development. Objective Here we examined neurochemical mechanisms underlying the formation of placebo effects in patients with Major Depressive Disorder (MDD). Participants Thirty-five medication-free MDD patients. Design and Intervention We performed a single-blinded two-week cross-over randomized controlled trial of two identical oral placebos (described as having either “active” or “inactive” fast-acting antidepressant-like effects) followed by a 10-week open-label treatment with a selective serotonin reuptake inhibitor (SSRI) or in some cases, another agent as clinically indicated. The volunteers were studied with PET and the μ-opioid receptor (MOR)-selective radiotracer [11C]carfentanil after each 1-week “inactive” and “active” oral placebo treatment. In addition, 1 mL of isotonic saline was administered intravenously (i.v.) within sight of the volunteer during PET scanning every 4 min over 20 min only after the 1-week active placebo treatment, with instructions that the compound may be associated with the activation of brain systems involved in mood improvement. This challenge stimulus was utilized to test the individual capacity to acutely activate endogenous opioid neurotransmision under expectations of antidepressant effect. Setting A University Health System. Main Outcomes and Measures Changes in depressive symptoms in response to “active” placebo and antidepressant. Baseline and activation measures of MOR binding. Results Higher baseline MOR binding in the nucleus accumbens (NAc) was associated with better response to antidepressant treatment (r=0.48; p=0.02). Reductions in depressive symptoms after 1-week of “active” placebo treatment, compared to the “inactive”, were associated with increased placebo-induced μ-opioid neurotransmission in a network of regions implicated in emotion, stress regulation, and the

  2. Differences in neural activity when processing emotional arousal and valence in autism spectrum disorders.

    PubMed

    Tseng, Angela; Wang, Zhishun; Huo, Yuankai; Goh, Suzanne; Russell, James A; Peterson, Bradley S

    2016-02-01

    Individuals with autism spectrum disorders (ASD) often have difficulty recognizing and interpreting facial expressions of emotion, which may impair their ability to navigate and communicate successfully in their social, interpersonal environments. Characterizing specific differences between individuals with ASD and their typically developing (TD) counterparts in the neural activity subserving their experience of emotional faces may provide distinct targets for ASD interventions. Thus we used functional magnetic resonance imaging (fMRI) and a parametric experimental design to identify brain regions in which neural activity correlated with ratings of arousal and valence for a broad range of emotional faces. Participants (51 ASD, 84 TD) were group-matched by age, sex, IQ, race, and socioeconomic status. Using task-related change in blood-oxygen-level-dependent (BOLD) fMRI signal as a measure, and covarying for age, sex, FSIQ, and ADOS scores, we detected significant differences across diagnostic groups in the neural activity subserving the dimension of arousal but not valence. BOLD-signal in TD participants correlated inversely with ratings of arousal in regions associated primarily with attentional functions, whereas BOLD-signal in ASD participants correlated positively with arousal ratings in regions commonly associated with impulse control and default-mode activity. Only minor differences were detected between groups in the BOLD signal correlates of valence ratings. Our findings provide unique insight into the emotional experiences of individuals with ASD. Although behavioral responses to face-stimuli were comparable across diagnostic groups, the corresponding neural activity for our ASD and TD groups differed dramatically. The near absence of group differences for valence correlates and the presence of strong group differences for arousal correlates suggest that individuals with ASD are not atypical in all aspects of emotion-processing. Studying these similarities

  3. Relation of obesity to neural activation in response to food commercials.

    PubMed

    Gearhardt, Ashley N; Yokum, Sonja; Stice, Eric; Harris, Jennifer L; Brownell, Kelly D

    2014-07-01

    Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. PMID:23576811

  4. Escargot and Scratch regulate neural commitment by antagonizing Notch activity in Drosophila sensory organs.

    PubMed

    Ramat, Anne; Audibert, Agnès; Louvet-Vallée, Sophie; Simon, Françoise; Fichelson, Pierre; Gho, Michel

    2016-08-15

    During Notch (N)-mediated binary cell fate decisions, cells adopt two different fates according to the levels of N pathway activation: an Noff-dependent or an Non-dependent fate. How cells maintain these N activity levels over time remains largely unknown. We address this question in the cell lineage that gives rise to the Drosophila mechanosensory organs. In this lineage a primary precursor cell undergoes a stereotyped sequence of oriented asymmetric cell divisions and transits through two neural precursor states before acquiring a neuron identity. Using a combination of genetic and cell biology strategies, we show that Escargot and Scratch, two transcription factors belonging to the Snail superfamily, maintain Noff neural commitment by directly blocking the transcription of N target genes. We propose that Snail factors act by displacing proneural transcription activators from DNA binding sites. As such, Snail factors maintain the Noff state in neural precursor cells by buffering any ectopic variation in the level of N activity. Since Escargot and Scratch orthologs are present in other precursor cells, our findings are fundamental for understanding precursor cell fate acquisition in other systems. PMID:27471258

  5. Model for a flexible motor memory based on a self-active recurrent neural network.

    PubMed

    Boström, Kim Joris; Wagner, Heiko; Prieske, Markus; de Lussanet, Marc

    2013-10-01

    Using recent recurrent network architecture based on the reservoir computing approach, we propose and numerically simulate a model that is focused on the aspects of a flexible motor memory for the storage of elementary movement patterns into the synaptic weights of a neural network, so that the patterns can be retrieved at any time by simple static commands. The resulting motor memory is flexible in that it is capable to continuously modulate the stored patterns. The modulation consists in an approximately linear inter- and extrapolation, generating a large space of possible movements that have not been learned before. A recurrent network of thousand neurons is trained in a manner that corresponds to a realistic exercising scenario, with experimentally measured muscular activations and with kinetic data representing proprioceptive feedback. The network is "self-active" in that it maintains recurrent flow of activation even in the absence of input, a feature that resembles the "resting-state activity" found in the human and animal brain. The model involves the concept of "neural outsourcing" which amounts to the permanent shifting of computational load from higher to lower-level neural structures, which might help to explain why humans are able to execute learned skills in a fluent and flexible manner without the need for attention to the details of the movement. PMID:24120277

  6. Neural substrates activated by viewing others expressing fatigue: a magnetoencephalography study.

    PubMed

    Ishii, Akira; Tanaka, Masaaki; Yamano, Emi; Watanabe, Yasuyoshi

    2012-05-21

    The neural substrates of the fatigue sensation have not been totally identified. Several lines of evidence demonstrate that seeing emotional changes in others activates brain regions involved in experiencing similar emotions. We hypothesized that there exists a mirror system regarding the fatigue sensation and that brain regions associated with the fatigue sensation may be activated by viewing other individuals expressing fatigue. In this study, we attempted to identify the neural substrates activated by viewing other fatigued individuals using magnetoencephalography (MEG). Twelve healthy participants were enrolled in our study after providing written informed consent. During MEG recordings, they viewed a set of pictures projected on a screen. The pictures, which were presented in a randomized order, were of a person with a fatigued or neutral facial expression. When participants viewed pictures of people with fatigued expressions, we were able to estimate equivalent current dipoles (ECDs) in the posterior cingulate cortex (PCC) in 9 of 12 participants approximately 300 ms after the onset of each picture presentation. When they viewed pictures of people with neutral expressions, we were not able to estimate corresponding ECDs for any participant. The PCC is the brain region activated by viewing others expressing fatigue, suggesting existence of the shared neural substrates of felt and observed fatigue. PMID:22502975

  7. Relation of obesity to neural activation in response to food commercials

    PubMed Central

    Yokum, Sonja; Stice, Eric; Harris, Jennifer L.; Brownell, Kelly D.

    2014-01-01

    Adolescents view thousands of food commercials annually, but the neural response to food advertising and its association with obesity is largely unknown. This study is the first to examine how neural response to food commercials differs from other stimuli (e.g. non-food commercials and television show) and to explore how this response may differ by weight status. The blood oxygen level-dependent functional magnetic resonance imaging activation was measured in 30 adolescents ranging from lean to obese in response to food and non-food commercials imbedded in a television show. Adolescents exhibited greater activation in regions implicated in visual processing (e.g. occipital gyrus), attention (e.g. parietal lobes), cognition (e.g. temporal gyrus and posterior cerebellar lobe), movement (e.g. anterior cerebellar cortex), somatosensory response (e.g. postcentral gyrus) and reward [e.g. orbitofrontal cortex and anterior cingulate cortex (ACC)] during food commercials. Obese participants exhibited less activation during food relative to non-food commercials in neural regions implicated in visual processing (e.g. cuneus), attention (e.g. posterior cerebellar lobe), reward (e.g. ventromedial prefrontal cortex and ACC) and salience detection (e.g. precuneus). Obese participants did exhibit greater activation in a region implicated in semantic control (e.g. medial temporal gyrus). These findings may inform current policy debates regarding the impact of food advertising to minors. PMID:23576811

  8. Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder

    PubMed Central

    Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

    2016-01-01

    Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

  9. Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder.

    PubMed

    Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

    2016-01-01

    Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

  10. Dopamine-induced dissociation of BOLD and neural activity in macaque visual cortex.

    PubMed

    Zaldivar, Daniel; Rauch, Alexander; Whittingstall, Kevin; Logothetis, Nikos K; Goense, Jozien

    2014-12-01

    Neuromodulators determine how neural circuits process information during cognitive states such as wakefulness, attention, learning, and memory. fMRI can provide insight into their function and dynamics, but their exact effect on BOLD responses remains unclear, limiting our ability to interpret the effects of changes in behavioral state using fMRI. Here, we investigated the effects of dopamine (DA) injections on neural responses and haemodynamic signals in macaque primary visual cortex (V1) using fMRI (7T) and intracortical electrophysiology. Aside from DA's involvement in diseases such as Parkinson's and schizophrenia, it also plays a role in visual perception. We mimicked DAergic neuromodulation by systemic injection of L-DOPA and Carbidopa (LDC) or by local application of DA in V1 and found that systemic application of LDC increased the signal-to-noise ratio (SNR) and amplitude of the visually evoked neural responses in V1. However, visually induced BOLD responses decreased, whereas cerebral blood flow (CBF) responses increased. This dissociation of BOLD and CBF suggests that dopamine increases energy metabolism by a disproportionate amount relative to the CBF response, causing the reduced BOLD response. Local application of DA in V1 had no effect on neural activity, suggesting that the dopaminergic effects are mediated by long-range interactions. The combination of BOLD-based and CBF-based fMRI can provide a signature of dopaminergic neuromodulation, indicating that the application of multimodal methods can improve our ability to distinguish sensory processing from neuromodulatory effects. PMID:25456449

  11. Deep neural nets as a method for quantitative structure-activity relationships.

    PubMed

    Ma, Junshui; Sheridan, Robert P; Liaw, Andy; Dahl, George E; Svetnik, Vladimir

    2015-02-23

    Neural networks were widely used for quantitative structure-activity relationships (QSAR) in the 1990s. Because of various practical issues (e.g., slow on large problems, difficult to train, prone to overfitting, etc.), they were superseded by more robust methods like support vector machine (SVM) and random forest (RF), which arose in the early 2000s. The last 10 years has witnessed a revival of neural networks in the machine learning community thanks to new methods for preventing overfitting, more efficient training algorithms, and advancements in computer hardware. In particular, deep neural nets (DNNs), i.e. neural nets with more than one hidden layer, have found great successes in many applications, such as computer vision and natural language processing. Here we show that DNNs can routinely make better prospective predictions than RF on a set of large diverse QSAR data sets that are taken from Merck's drug discovery effort. The number of adjustable parameters needed for DNNs is fairly large, but our results show that it is not necessary to optimize them for individual data sets, and a single set of recommended parameters can achieve better performance than RF for most of the data sets we studied. The usefulness of the parameters is demonstrated on additional data sets not used in the calibration. Although training DNNs is still computationally intensive, using graphical processing units (GPUs) can make this issue manageable. PMID:25635324

  12. Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans.

    PubMed

    Cheesman, Hilary K; Feinbaum, Rhonda L; Thekkiniath, Jose; Dowen, Robert H; Conery, Annie L; Pukkila-Worley, Read

    2016-03-01

    Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C. elegans from bacterial infection by inducing immune effector expression via the conserved p38 MAP kinase pathway, but was toxic to nematodes developing in the absence of pathogen. To investigate a possible connection between the toxicity and immunostimulatory properties of this xenobiotic, we conducted a forward genetic screen for C. elegans mutants that are resistant to the deleterious effects of the compound, and identified five toxicity suppressors. These strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1, and pmk-1), demonstrating that hyperstimulation of the p38 MAPK pathway is toxic to animals. To explore mechanisms of immune pathway regulation in C. elegans, we conducted another genetic screen for dominant activators of the p38 MAPK pathway, and identified a single allele that had a gain-of-function (gf) mutation in nsy-1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1. The nsy-1(gf) allele caused hyperinduction of p38 MAPK PMK-1-dependent immune effectors, had greater levels of phosphorylated p38 MAPK, and was more resistant to killing by the bacterial pathogen Pseudomonas aeruginosa compared to wild-type controls. In addition, the nsy-1(gf) mutation was toxic to developing animals. Together, these data suggest that the activity of the MAPKKK NSY-1 is tightly regulated as part of a physiological mechanism to control p38 MAPK-mediated innate immune hyperactivation, and ensure cellular homeostasis in C. elegans. PMID:26818074

  13. Aberrant Activation of p38 MAP Kinase-Dependent Innate Immune Responses Is Toxic to Caenorhabditis elegans

    PubMed Central

    Cheesman, Hilary K.; Feinbaum, Rhonda L.; Thekkiniath, Jose; Dowen, Robert H.; Conery, Annie L.; Pukkila-Worley, Read

    2016-01-01

    Inappropriate activation of innate immune responses in intestinal epithelial cells underlies the pathophysiology of inflammatory disorders of the intestine. Here we examine the physiological effects of immune hyperactivation in the intestine of the nematode Caenorhabditis elegans. We previously identified an immunostimulatory xenobiotic that protects C. elegans from bacterial infection by inducing immune effector expression via the conserved p38 MAP kinase pathway, but was toxic to nematodes developing in the absence of pathogen. To investigate a possible connection between the toxicity and immunostimulatory properties of this xenobiotic, we conducted a forward genetic screen for C. elegans mutants that are resistant to the deleterious effects of the compound, and identified five toxicity suppressors. These strains contained hypomorphic mutations in each of the known components of the p38 MAP kinase cassette (tir-1, nsy-1, sek-1, and pmk-1), demonstrating that hyperstimulation of the p38 MAPK pathway is toxic to animals. To explore mechanisms of immune pathway regulation in C. elegans, we conducted another genetic screen for dominant activators of the p38 MAPK pathway, and identified a single allele that had a gain-of-function (gf) mutation in nsy-1, the MAP kinase kinase kinase that acts upstream of p38 MAPK pmk-1. The nsy-1(gf) allele caused hyperinduction of p38 MAPK PMK-1-dependent immune effectors, had greater levels of phosphorylated p38 MAPK, and was more resistant to killing by the bacterial pathogen Pseudomonas aeruginosa compared to wild-type controls. In addition, the nsy-1(gf) mutation was toxic to developing animals. Together, these data suggest that the activity of the MAPKKK NSY-1 is tightly regulated as part of a physiological mechanism to control p38 MAPK-mediated innate immune hyperactivation, and ensure cellular homeostasis in C. elegans. PMID:26818074

  14. Aberrant expression of homeobox gene SIX1 in Hodgkin lymphoma

    PubMed Central

    Nagel, Stefan; Meyer, Corinna; Kaufmann, Maren; Drexler, Hans G.; MacLeod, Roderick A.F.

    2015-01-01

    In Hodgkin lymphoma (HL) we recently identified deregulated expression of homeobox genes MSX1 and OTX2 which are physiologically involved in development of the embryonal neural plate border region. Here, we examined in HL homeobox gene SIX1 an additional regulator of this embryonal region mediating differentiation of placodal precursors. SIX1 was aberrantly activated in 12 % of HL patient samples in silico, indicating a pathological role in a subset of this B-cell malignancy. In addition, SIX1 expression was detected in HL cell lines which were used as models to reveal upstream factors and target genes of this basic developmental regulator. We detected increased copy numbers of the SIX1 locus at chromosome 14q23 correlating with enhanced expression while chromosomal translocations were absent. Moreover, comparative expression profiling data and pertinent gene modulation experiments indicated that the WNT-signalling pathway and transcription factor MEF2C regulate SIX1 expression. Genes encoding the transcription factors GATA2, GATA3, MSX1 and SPIB – all basic lymphoid regulators - were identified as targets of SIX1 in HL. In addition, cofactors EYA1 and TLE4, respectively, contrastingly mediated activation and suppression of SIX1 target gene expression. Thus, the protein domain interfaces may represent therapeutic targets in SIX1-positive HL subsets. Collectively, our data reveal a gene regulatory network with SIX1 centrally deregulating lymphoid differentiation and support concordance of lymphopoiesis/lymphomagenesis and developmental processes in the neural plate border region. PMID:26473286

  15. Mutual information and self-control of a fully-connected low-activity neural network

    NASA Astrophysics Data System (ADS)

    Bollé, D.; Carreta, D. Dominguez

    2000-11-01

    A self-control mechanism for the dynamics of a three-state fully connected neural network is studied through the introduction of a time-dependent threshold. The self-adapting threshold is a function of both the neural and the pattern activity in the network. The time evolution of the order parameters is obtained on the basis of a recently developed dynamical recursive scheme. In the limit of low activity the mutual information is shown to be the relevant parameter in order to determine the retrieval quality. Due to self-control an improvement of this mutual information content as well as an increase of the storage capacity and an enlargement of the basins of attraction are found. These results are compared with numerical simulations.

  16. Perception of race-related features modulates neural activity associated with action observation and imitation.

    PubMed

    Earls, Holly A; Englander, Zoë A; Morris, James P

    2013-05-29

    The present study examines whether race-specific features affect biological motion perception. Activation of the neural action observation and imitation network was measured using functional MRI. During scanning, individuals were asked to imitate and observe basic hand movements of own-race and other-race actors. Results indicate that three key areas often associated with action observation and imitation, the inferior parietal lobule, superior parietal lobule, and superior temporal sulcus, were more active when participants imitated and observed hand movements of own-race relative to other-race actors. These findings indicate that several regions associated with the neural imitation/observation network are sensitive to race-related features. PMID:23571693

  17. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells.

    PubMed

    Luo, Yuping; Coskun, Volkan; Liang, Aibing; Yu, Juehua; Cheng, Liming; Ge, Weihong; Shi, Zhanping; Zhang, Kunshan; Li, Chun; Cui, Yaru; Lin, Haijun; Luo, Dandan; Wang, Junbang; Lin, Connie; Dai, Zachary; Zhu, Hongwen; Zhang, Jun; Liu, Jie; Liu, Hailiang; deVellis, Jean; Horvath, Steve; Sun, Yi Eve; Li, Siguang

    2015-05-21

    The scarcity of tissue-specific stem cells and the complexity of their surrounding environment have made molecular characterization of these cells particularly challenging. Through single-cell transcriptome and weighted gene co-expression network analysis (WGCNA), we uncovered molecular properties of CD133(+)/GFAP(-) ependymal (E) cells in the adult mouse forebrain neurogenic zone. Surprisingly, prominent hub genes of the gene network unique to ependymal CD133(+)/GFAP(-) quiescent cells were enriched for immune-responsive genes, as well as genes encoding receptors for angiogenic factors. Administration of vascular endothelial growth factor (VEGF) activated CD133(+) ependymal neural stem cells (NSCs), lining not only the lateral but also the fourth ventricles and, together with basic fibroblast growth factor (bFGF), elicited subsequent neural lineage differentiation and migration. This study revealed the existence of dormant ependymal NSCs throughout the ventricular surface of the CNS, as well as signals abundant after injury for their activation. PMID:26000486

  18. Atypical Neural Activity in Males But Not Females with Autism Spectrum Disorder.

    PubMed

    Kirkovski, Melissa; Enticott, Peter G; Hughes, Matthew E; Rossell, Susan L; Fitzgerald, Paul B

    2016-03-01

    The medial prefrontal cortex (mPFC) and the right temporo-parietal junction (rTPj) are highly involved in social understanding, a core area of impairment in autism spectrum disorder (ASD). We used fMRI to investigate sex differences in the neural correlates of social understanding in 27 high-functioning adults with ASD and 23 matched controls. There were no differences in neural activity in the mPFC or rTPj between groups during social processing. Whole brain analysis revealed decreased activity in the posterior superior temporal sulcus in males with ASD compared to control males while processing social information. This pattern was not observed in the female sub-sample. The current study indicates that sex mediates the neurobiology of ASD, particularly with respect to processing social information. PMID:26520145

  19. Thermal dependence of neural activity in the hamster hippocampal slice preparation

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Thomas, M. P.; Eckerman, P.

    1987-01-01

    1. Neural activity was recorded in an in vitro hamster hippocampal slice preparation while the temperature of the Ringer's solution bathing in the slice was controlled at selected levels. 2. The amplitude of the population spike (action potentials from a group of pyramidal cells) was measured as bath temperature was lowered from 35 degrees C to temperatures where a response could not be evoked. 3. Plots of population spike amplitude versus temperature have bell-shaped curves. The population spikes increased in amplitude as temperature was lowered from 35 degrees C, reached a peak amplitude between 25 and 20 degrees C, and then decreased until a response could not be evoked when temperature was further lowered. 4. These in vitro results obtained in the slice preparation are related to in vivo hippocampal studies. Results are interpreted as consistent with the proposal reviewed here that neural activity in the hippocampus plays a role at specific stages of entrance into and arousal from hibernation.

  20. Association between vasovagal hypotension and low sympathetic neural activity during presyncope

    NASA Technical Reports Server (NTRS)

    Cooke, William H.; Convertino, Victor A.

    2002-01-01

    Recent studies suggest that an underlying mechanism for susceptibility of patients and astronauts to presyncope includes hypoadrenergic responses to orthostatic stress. However, data used to reach this conclusion are open to various interpretations. In this report, maintenance of sympathetic neural activity (MSNA; peroneal nerve microneurography) during -60 mmHg lower body negative pressure (LBNP) was associated with maintenance of orthostatic tolerance, and disappearance of MSNA was associated with hypotension and pre-syncope. However, MSNA was substantially higher during progressive increases of negative pressure in the presyncopal subject, compared to the non-presyncopal subjects. The data from this case report question the notion that orthostatic hypotension occurs due to inadequate sympathetic neural activation during orthostatic stress in apparently normal, healthy subjects.

  1. Category-based induction from similarity of neural activation.

    PubMed

    Weber, Matthew J; Osherson, Daniel

    2014-03-01

    The idea that similarity might be an engine of inductive inference dates back at least as far as David Hume. However, Hume's thesis is difficult to test without begging the question, since judgments of similarity may be infected by inferential processes. We present a one-parameter model of category-based induction that generates predictions about arbitrary statements of conditional probability over a predicate and a set of items. The prediction is based on the unconditional probabilities and similarities that characterize that predicate and those items. To test Hume's thesis, we collected brain activation from various regions of the ventral visual stream during a categorization task that did not invite comparison of categories. We then calculated the similarity of those activation patterns using a simple measure of vectorwise similarity and supplied those similarities to the model. The model's outputs correlated well with subjects' judgments of conditional probability. Our results represent a promising first step toward confirming Hume's thesis; similarity, assessed without reference to induction, may well drive inductive inference. PMID:24254747

  2. Persistent Activation of NF-κB in BRCA1-Deficient Mammary Progenitors Drives Aberrant Proliferation and Accumulation of DNA Damage.

    PubMed

    Sau, Andrea; Lau, Rosanna; Cabrita, Miguel A; Nolan, Emma; Crooks, Peter A; Visvader, Jane E; Pratt, M A Christine

    2016-07-01

    Human BRCA1 mutation carriers and BRCA1-deficient mouse mammary glands contain an abnormal population of mammary luminal progenitors that can form 3D colonies in a hormone-independent manner. The intrinsic cellular regulatory defect in these presumptive breast cancer precursors is not known. We have discovered that nuclear factor kappaB (NF-κB) (p52/RelB) is persistently activated in a subset of BRCA1-deficient mammary luminal progenitors. Hormone-independent luminal progenitor colony formation required NF-κB, ataxia telangiectasia-mutated (ATM), and the inhibitor of kappaB kinase, IKKα. Progesterone (P4)-stimulated proliferation resulted in a marked enhancement of DNA damage foci in Brca1(-/-) mouse mammary. In vivo, NF-κB inhibition prevented recovery of Brca1(-/-) hormone-independent colony-forming cells. The majority of human BRCA1(mut/+) mammary glands showed marked lobular expression of nuclear NF-κB. We conclude that the aberrant proliferative capacity of Brca1(-/-) luminal progenitor cells is linked to the replication-associated DNA damage response, where proliferation of mammary progenitors is perpetuated by damage-induced, autologous NF-κB signaling. PMID:27292187

  3. Determination of genotoxic effects of Imazethapyr herbicide in Allium cepa root cells by mitotic activity, chromosome aberration, and comet assay.

    PubMed

    Liman, Recep; Ciğerci, İbrahim Hakkı; Öztürk, Nur Serap

    2015-02-01

    Imazethapyr (IM) is an imidazolinone herbicide that is currently used for broad-spectrum weed control in soybean and other legume crops. In this study, cytotoxic and genotoxic effects of IM were investigated by using mitotic index (MI), mitotic phases, chromosomal abnormalities (CAs) and DNA damage on the root meristem cells of Allium cepa. In Allium root growth inhibition test, EC50 value was determined as 20 ppm, and 0.5xEC50, EC50 and 2xEC50 concentrations of IM herbicide were introduced to onion tuber roots. Distilled water and methyl methane sulfonate (MMS, 10 mg/L) were used as a negative and positive control, respectively. As A. cepa cell cycle is 24 hours, so, application process was carried out for 24, 48, 72 and 96 hours. All the applied doses decreased MIs compared to control group and these declines were found to be statistically meaningful. Analysis of the chromosomes showed that 10 ppm IM except for 48 h induced CAs but 40 ppm IM except for 72 h decreased CAs. DNA damage was found significantly higher in 20 and 40 ppm of IM compared to the control in comet assay. These results indicated that IM herbicide exhibits cytotoxic activity but not genotoxic activity (except 10 ppm) and induced DNA damage in a dose dependent manner in A. cepa root meristematic cells. PMID:25752428

  4. BOLD Responses in Human Primary Visual Cortex are Insensitive to Substantial Changes in Neural Activity.

    PubMed

    Swettenham, J B; Muthukumaraswamy, S D; Singh, K D

    2013-01-01

    The relationship between blood oxygenation level dependent-functional magnetic resonance imaging (BOLD-fMRI) and magnetoencephalography (MEG) metrics were explored using low-level visual stimuli known to elicit a rich variety of neural responses. Stimuli were either perceptually isoluminant red/green or luminance-modulated black/yellow square-wave gratings with spatial frequencies of 0.5, 3, and 6 cycles per degree. Neural responses were measured with BOLD-fMRI (3-tesla) and whole head MEG. For all stimuli, the BOLD response showed bilateral activation of early visual cortex that was greater in the contralateral hemisphere. There was variation between individuals but weak, or no evidence, of amplitude dependence on either spatial frequency or the presence of luminance contrast. In contrast, beamformer analysis of MEG data showed activation in contralateral early visual cortex and revealed: (i) evoked responses with stimulus-dependent amplitude and latency; (ii) gamma and high-beta oscillations, with spatial frequency dependent peaks at approximately 30 and 50 Hz, but only for luminance-modulated gratings; (iii) The gamma and beta oscillations appeared to show different spatial frequency tuning profiles; (iv) much weaker gamma and beta responses, and at higher oscillation frequencies, for isoluminant compared to luminance-modulated gratings. The results provide further evidence that the relationship between the fMRI-BOLD response and cortical neural activity is complex, with BOLD-fMRI being insensitive to substantial changes in neural activity. All stimuli were clearly visible to participants and so the paucity of gamma oscillations to isoluminant stimuli is inconsistent with theories of their role in conscious visual perception. PMID:23482840

  5. Prediction of Spatiotemporal Patterns of Neural Activity from Pairwise Correlations

    NASA Astrophysics Data System (ADS)

    Marre, O.; El Boustani, S.; Frégnac, Y.; Destexhe, A.

    2009-04-01

    We designed a model-based analysis to predict the occurrence of population patterns in distributed spiking activity. Using a maximum entropy principle with a Markovian assumption, we obtain a model that accounts for both spatial and temporal pairwise correlations among neurons. This model is tested on data generated with a Glauber spin-glass system and is shown to correctly predict the occurrence probabilities of spatiotemporal patterns significantly better than Ising models only based on spatial correlations. This increase of predictability was also observed on experimental data recorded in parietal cortex during slow-wave sleep. This approach can also be used to generate surrogates that reproduce the spatial and temporal correlations of a given data set.

  6. Prediction of Spatiotemporal Patterns of Neural Activity from Pairwise Correlations

    SciTech Connect

    Marre, O.; El Boustani, S.; Fregnac, Y.; Destexhe, A.

    2009-04-03

    We designed a model-based analysis to predict the occurrence of population patterns in distributed spiking activity. Using a maximum entropy principle with a Markovian assumption, we obtain a model that accounts for both spatial and temporal pairwise correlations among neurons. This model is tested on data generated with a Glauber spin-glass system and is shown to correctly predict the occurrence probabilities of spatiotemporal patterns significantly better than Ising models only based on spatial correlations. This increase of predictability was also observed on experimental data recorded in parietal cortex during slow-wave sleep. This approach can also be used to generate surrogates that reproduce the spatial and temporal correlations of a given data set.

  7. Spontaneous neural activity in the primary visual cortex of retinal degenerated rats.

    PubMed

    Wang, Yi; Chen, Ke; Xu, Ping; Ng, Tsz Kin; Chan, Leanne Lai Hang

    2016-06-01

    Retinal degeneration (RD) models have been widely used to study retinal degenerative diseases for a long time. The biological and electrophysiological presentations of changes in the retina during degeneration progress have been well investigated; thus, the present study is aimed at investigating the electrophysiological effects of RD in the primary visual cortex. We extracellularly recorded the spontaneous neural activities in the primary visual cortex of RD rats. The firing rate, interspike interval (ISI) and Lempel-Ziv (LZ) complexity of spontaneous neural activities were subsequently analyzed. When compared to the control group, it was found that the neurons in primary visual cortex of the RD model fired more frequently. In addition, there was a decrease in LZ complexity of spontaneous neural firing in the RD model. These results suggest that the progress of RD may not only affect the retina itself but also the primary visual cortex, which may result in an unbalanced inhibition-excitation system as well as the decreased arising rate of new patterns of spontaneous activities. PMID:27132087

  8. Optical imaging of fast light-evoked fast neural activation in amphibian retina

    NASA Astrophysics Data System (ADS)

    Yao, Xin-Cheng; George, John S.

    2006-02-01

    High performance functional imaging is needed for dynamic measurements of neural processing in retina. Emerging techniques of visual prosthesis also require advanced methodology for reliable validation of electromagnetic stimulation of the retina. Imaging of fast intrinsic optical responses associated with neural activation promises a variety of technical advantages over traditional single and multi-channel electrophysiological techniques for these purposes, but the application of fast optical signals for neural imaging has been limited by low signal to noise ratio and high background light intensity. However, using optimized near infrared probe light and improved optical systems, we have improved the optical signals substantially, allowing single pass measurements. Fast photodiode measurements typically disclose dynamic transmitted light changes of whole retina at the level of 10 -4 dI/I, where dI is the dynamic optical change and I is the baseline light intensity. Using a fast high performance CCD, we imaged fast intrinsic optical responses from isolated retina activated by a visible light flash. Fast, high resolution imaging disclosed larger local optical responses, and showed evidence of multiple response components with both negative- and positive-going signals, on different timescales. Darkfield imaging techniques further enhanced the sensitivity of optical measurements. At single cell resolution, brightfield imaging disclosed maxima of optical responses ~5% dI/I, while darkfield imaging showed maxima of optical responses exceeding 10% dI/I. In comparison with simultaneous electrophysiological recording, optical imaging provided much better localized patterns of response over the activated area of the retina.

  9. ACTIVATION OF PERK KINASE IN NEURAL CELLS BY PROTEASOME INHIBITOR TREATMENT

    PubMed Central

    Zhang, Le; Ebenezer, Philip J; Dasuri, Kalavathi; Bruce-Keller, Annadora J.; Fernandez-Kim, Sun Ok; Liu, Ying; Keller, Jeffrey N.

    2010-01-01

    Inhibition of the proteasome proteolytic pathway occurs as the result of normal aging, as well as in a variety of neurodegenerative conditions, and is believed to promote cellular toxicity in each of these conditions through diverse mechanisms. In the present study we examined whether proteasome inhibition alters the protein kinase (PKR)-like ER kinase (PERK). Our studies demonstrate that proteasome inhibitors induce the transient activation of PERK in both primary rat neurons as well as the N2a neural cell line. Experiments with siRNA to PERK demonstrated that the modulation of PERK was not significant involved in regulating toxicity, ubiquitinated protein levels, or ribosome perturbations in response to proteasome inhibitor treatment. Surprisingly, PERK was observed to be involved in the upregulation of p38 kinase following proteasome inhibitor treatment. Taken together, these data demonstrate the ability of proteasome inhibition to activate PERK and demonstrate evidence for novel cross talk between PERK and the activation of p38 kinase in neural cells following proteasome inhibition. Taken together, these data have implications for understanding the basis by which proteasome inhibition alters neural homeostasis, and the basis by which cell signaling cascades are regulated by proteasome inhibition. PMID:19860852

  10. Kinetics of exercise-induced neural activation; interpretive dilemma of altered cerebral perfusion.

    PubMed

    Miyazawa, Taiki; Horiuchi, Masahiro; Ichikawa, Daisuke; Sato, Kohei; Tanaka, Naoki; Bailey, Damian M; Ogoh, Shigehiko

    2012-02-01

    Neural activation decreases cerebral deoxyhaemoglobin (HHb(C)) and increases oxyhaemoglobin concentration (O(2)Hb(C)). In contrast, patients who present with restricted cerebral blood flow, such as those suffering from cerebral ischaemia or Alzheimer's disease, and during the course of ageing the converse occurs, in that HHb(C) increases and O(2)Hb(C) decreases during neural activation. In the present study, we examined the interpretive implications of altered exercise-induced cerebral blood flow for cortical oxygenation in healthy subjects. Both O(2)Hb(C) and HHb(C) (prefrontal cortex) were determined in 11 healthy men using near-infrared spectroscopy (NIRS). Middle cerebral artery mean blood velocity (MCA V(mean)) was determined via transcranial Doppler ultrasonography. Measurements were performed during contralateral hand-grip exercise during suprasystolic bilateral thigh-cuff occlusion (Cuff+) and within 2 s of cuff release (Cuff-) for the acute manipulation of cerebral perfusion. During Cuff+, both MCA V(mean) and O(2)Hb(C) increased during exercise, whereas HHb(C) decreased. In contrast, the opposite occurred during the Cuff- manipulation. These findings highlight the inverse relationship between cerebral blood flow and cerebral oxygenation as determined by NIRS, which has interpretive implications for the kinetics underlying exercise-induced neural activation. PMID:22041980

  11. Dynamics of modularity of neural activity in the brain during development

    NASA Astrophysics Data System (ADS)

    Deem, Michael; Chen, Man

    2014-03-01

    Theory suggests that more modular systems can have better response functions at short times. This theory suggests that greater cognitive performance may be achieved for more modular neural activity, and that modularity of neural activity may, therefore, likely increase with development in children. We study the relationship between age and modularity of brain neural activity in developing children. The value of modularity calculated from fMRI data is observed to increase during childhood development and peak in young adulthood. We interpret these results as evidence of selection for plasticity in the cognitive function of the human brain. We present a model to illustrate how modularity can provide greater cognitive performance at short times and enhance fast, low-level, automatic cognitive processes. Conversely, high-level, effortful, conscious cognitive processes may not benefit from modularity. We use quasispecies theory to predict how the average modularity evolves with age, given a fitness function extracted from the model. We suggest further experiments exploring the effect of modularity on cognitive performance and suggest that modularity may be a potential biomarker for injury, rehabilitation, or disease.

  12. Afferent vagal nerve stimulation resets baroreflex neural arc and inhibits sympathetic nerve activity

    PubMed Central

    Saku, Keita; Kishi, Takuya; Sakamoto, Kazuo; Hosokawa, Kazuya; Sakamoto, Takafumi; Murayama, Yoshinori; Kakino, Takamori; Ikeda, Masataka; Ide, Tomomi; Sunagawa, Kenji

    2014-01-01

    Abstract It has been established that vagal nerve stimulation (VNS) benefits patients and/or animals with heart failure. However, the impact of VNS on sympathetic nerve activity (SNA) remains unknown. In this study, we investigated how vagal afferent stimulation (AVNS) impacts baroreflex control of SNA. In 12 anesthetized Sprague–Dawley rats, we controlled the pressure in isolated bilateral carotid sinuses (CSP), and measured splanchnic SNA and arterial pressure (AP). Under a constant CSP, increasing the voltage of AVNS dose dependently decreased SNA and AP. The averaged maximal inhibition of SNA was ‐28.0 ± 10.3%. To evaluate the dynamic impacts of AVNS on SNA, we performed random AVNS using binary white noise sequences, and identified the transfer function from AVNS to SNA and that from SNA to AP. We also identified transfer functions of the native baroreflex from CSP to SNA (neural arc) and from SNA to AP (peripheral arc). The transfer function from AVNS to SNA strikingly resembled the baroreflex neural arc and the transfer functions of SNA to AP were indistinguishable whether we perturbed ANVS or CSP, indicating that they likely share common central and peripheral neural mechanisms. To examine the impact of AVNS on baroreflex, we changed CSP stepwise and measured SNA and AP responses with or without AVNS. AVNS resets the sigmoidal neural arc downward, but did not affect the linear peripheral arc. In conclusion, AVNS resets the baroreflex neural arc and induces sympathoinhibition in the same manner as the control of SNA and AP by the native baroreflex. PMID:25194023

  13. Aberrantly activated claudin 6 and 18.2 as potential therapy targets in non-small-cell lung cancer.

    PubMed

    Micke, Patrick; Mattsson, Johanna Sofia Margareta; Edlund, Karolina; Lohr, Miriam; Jirström, Karin; Berglund, Anders; Botling, Johan; Rahnenfuehrer, Jörg; Marincevic, Millaray; Pontén, Fredrik; Ekman, Simon; Hengstler, Jan; Wöll, Stefan; Sahin, Ugur; Türeci, Ozlem

    2014-11-01

    Claudins (CLDNs) are central components of tight junctions that regulate epithelial-cell barrier function and polarity. Altered CLDN expression patterns have been demonstrated in numerous cancer types and lineage-specific CLDNs have been proposed as therapy targets. The objective of this study was to assess which fraction of patients with non-small-cell lung cancer (NSCLC) express CLDN6 and CLDN18 isoform 2 (CLDN18.2). Protein expression of CLDN6 and CLDN18.2 was examined by immunohistochemistry on a tissue microarray (n = 355) and transcript levels were supportively determined based on gene expression microarray data from fresh-frozen NSCLC tissues (n = 196). Both were analyzed with regard to frequency, distribution and association with clinical parameters. Immunohistochemical analysis of tissue sections revealed distinct membranous positivity of CLDN6 (6.5%) and CLDN18.2 (3.7%) proteins in virtually non-overlapping subgroups of adenocarcinomas and large-cell carcinomas. Pneumocytes and bronchial epithelial cells were consistently negative. Corresponding to the protein expression, in subsets of non-squamous lung carcinoma high mRNA levels of CLDN6 (7-16%) and total CLDN18 (5-12%) were observed. Protein expression correlated well with total mRNA expression of the corresponding gene (rho = 0.4-0.8). CLDN18.2 positive tumors were enriched among slowly proliferating, thyroid transcription factor 1 (TTF-1)-negative adenocarcinomas, suggesting that isoform-specific CLDN expression may delineate a specific subtype. Noteworthy, high CLDN6 protein expression was associated with worse prognosis in lung adenocarcinoma in the univariate [hazard ratio (HR): 1.8; p = 0.03] and multivariate COX regression model (HR: 1.9; p = 0.02). These findings encourage further clinical exploration of targeting ectopically activated CLDN expression as a valuable treatment concept in NSCLC. PMID:24710653

  14. Noise influence on spike activation in a Hindmarsh–Rose small-world neural network

    NASA Astrophysics Data System (ADS)

    Zhe, Sun; Micheletto, Ruggero

    2016-07-01

    We studied the role of noise in neural networks, especially focusing on its relation to the propagation of spike activity in a small sized system. We set up a source of information using a single neuron that is constantly spiking. This element called initiator x o feeds spikes to the rest of the network that is initially quiescent and subsequently reacts with vigorous spiking after a transitional period of time. We found that noise quickly suppresses the initiator’s influence and favors spontaneous spike activity and, using a decibel representation of noise intensity, we established a linear relationship between noise amplitude and the interval from the initiator’s first spike and the rest of the network activation. We studied the same process with networks of different sizes (number of neurons) and found that the initiator x o has a measurable influence on small networks, but as the network grows in size, spontaneous spiking emerges disrupting its effects on networks of more than about N = 100 neurons. This suggests that the mechanism of internal noise generation allows information transmission within a small neural neighborhood, but decays for bigger network domains. We also analyzed the Fourier spectrum of the whole network membrane potential and verified that noise provokes the reduction of main θ and α peaks before transitioning into chaotic spiking. However, network size does not reproduce a similar phenomena; instead we recorded a reduction in peaks’ amplitude, a better sharpness and definition of Fourier peaks, but not the evident degeneration to chaos observed with increasing external noise. This work aims to contribute to the understanding of the fundamental mechanisms of propagation of spontaneous spiking in neural networks and gives a quantitative assessment of how noise can be used to control and modulate this phenomenon in Hindmarsh‑Rose (H‑R) neural networks.

  15. Rejuvenation of MPTP-induced human neural precursor cell senescence by activating autophagy

    SciTech Connect

    Zhu, Liang; Dong, Chuanming; Sun, Chenxi; Ma, Rongjie; Yang, Danjing; Zhu, Hongwen; Xu, Jun

    2015-08-21

    Aging of neural stem cell, which can affect brain homeostasis, may be caused by many cellular mechanisms. Autophagy dysfunction was found in aged and neurodegenerative brains. However, little is known about the relationship between autophagy and human neural stem cell (hNSC) aging. The present study used 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to treat neural precursor cells (NPCs) derived from human embryonic stem cell (hESC) line H9 and investigate related molecular mechanisms involved in this process. MPTP-treated NPCs were found to undergo premature senescence [determined by increased senescence-associated-β-galactosidase (SA-β-gal) activity, elevated intracellular reactive oxygen species level, and decreased proliferation] and were associated with impaired autophagy. Additionally, the cellular senescence phenotypes were manifested at the molecular level by a significant increase in p21 and p53 expression, a decrease in SOD2 expression, and a decrease in expression of some key autophagy-related genes such as Atg5, Atg7, Atg12, and Beclin 1. Furthermore, we found that the senescence-like phenotype of MPTP-treated hNPCs was rejuvenated through treatment with a well-known autophagy enhancer rapamycin, which was blocked by suppression of essential autophagy gene Beclin 1. Taken together, these findings reveal the critical role of autophagy in the process of hNSC aging, and this process can be reversed by activating autophagy. - Highlights: • We successfully establish hESC-derived neural precursor cells. • MPTP treatment induced senescence-like state in hESC-derived NPCs. • MPTP treatment induced impaired autophagy of hESC-derived NPCs. • MPTP-induced hESC-derived NPC senescence was rejuvenated by activating autophagy.

  16. Long-range neural activity evoked by premotor cortex stimulation: a TMS/EEG co-registration study

    PubMed Central

    Zanon, Marco; Battaglini, Piero P.; Jarmolowska, Joanna; Pizzolato, Gilberto; Busan, Pierpaolo

    2013-01-01

    The premotor cortex is one of the fundamental structures composing the neural networks of the human brain. It is implicated in many behaviors and cognitive tasks, ranging from movement to attention and eye-related activity. Therefore, neural circuits that are related to premotor cortex have been studied to clarify their connectivity and/or role in different tasks. In the present work, we aimed to investigate the propagation of the neural activity evoked in the dorsal premotor cortex using transcranial magnetic stimulation/electroencephalography (TMS/EEG). Toward this end, interest was focused on the neural dynamics elicited in long-ranging temporal and spatial networks. Twelve healthy volunteers underwent a single-pulse TMS protocol in a resting condition with eyes closed, and the evoked activity, measured by EEG, was compared to a sham condition in a time window ranging from 45 ms to about 200 ms after TMS. Spatial and temporal investigations were carried out with sLORETA. TMS was found to induce propagation of neural activity mainly in the contralateral sensorimotor and frontal cortices, at about 130 ms after delivery of the stimulus. Different types of analyses showed propagated activity also in posterior, mainly visual, regions, in a time window between 70 and 130 ms. Finally, a likely “rebounding” activation of the sensorimotor and frontal regions, was observed in various time ranges. Taken together, the present findings further characterize the neural circuits that are driven by dorsal premotor cortex activation in healthy humans. PMID:24324426

  17. The Synapse Project: Engagement in mentally challenging activities enhances neural efficiency

    PubMed Central

    McDonough, Ian M.; Haber, Sara; Bischof, Gérard N.; Park, Denise C.

    2015-01-01

    Purpose: Correlational and limited experimental evidence suggests that an engaged lifestyle is associated with the maintenance of cognitive vitality in old age. However, the mechanisms underlying these engagement effects are poorly understood. We hypothesized that mental effort underlies engagement effects and used fMRI to examine the impact of high-challenge activities (digital photography and quilting) compared with low-challenge activities (socializing or performing low-challenge cognitive tasks) on neural function at pretest, posttest, and one year after the engagement program. Methods: In the scanner, participants performed a semantic-classification task with two levels of difficulty to assess the modulation of brain activity in response to task demands. Results: The High-Challenge group, but not the Low-Challenge group, showed increased modulation of brain activity in medial frontal, lateral temporal, and parietal cortex—regions associated with attention and semantic processing—some of which were maintained a year later. This increased modulation stemmed from decreases in brain activity during the easy condition for the High-Challenge group and was associated with time committed to the program, age, and cognition. Conclusions: Sustained engagement in cognitively demanding activities facilitated cognition by increasing neural efficiency. Mentally-challenging activities may be neuroprotective and an important element to maintaining a healthy brain into late adulthood. PMID:26484698

  18. Soy Saponins Meditate the Progression of Colon Cancer in Rats by Inhibiting the Activity of β-Glucuronidase and the Number of Aberrant Crypt Foci but Not Cyclooxygenase-2 Activity

    PubMed Central

    Guo, Yu-Wei; Chen, Yue-Hwa; Liao, Hsiang; Lin, Shyh-Hsiang

    2013-01-01

    Objective. The effect of extracted crude soybean saponins on preneoplastic lesions, aberrant crypt foci (ACF), and the related mechanism were investigated. Research Methods and Procedures. Rats were assigned into five groups according to different doses of extracted crude soybean saponins and received 1,2-dimethylhydrazine (DMH) injection in week 5. In week 15, all rats were sacrificed. The number of ACFs, the cyclooxygenase-2 (COX-2) protein expression, the level of prostaglandins E2 (PGE2), and the activity of β-glucuronidase were examined. Results. Results revealed that the consumption of extracted crude soybean saponins decreased the number of ACFs and the activity of β-glucuronidase in rats, while the expression of COX-2 protein and PGE2 level were not affected. Conclusions. Soybean saponins were effective in inhibiting colon cancer by downregulating the activity of β-glucuronidase in colonic mucosa but not the COX-2 protein expression and PGE2 level. PMID:24224098

  19. Perceptual Salience and Reward Both Influence Feedback-Related Neural Activity Arising from Choice.

    PubMed

    Lou, Bin; Hsu, Wha-Yin; Sajda, Paul

    2015-09-23

    expected reward. Here, we use electroencephelography to identify trial-by-trial neural activity of perceived stimulus salience, showing that this activity can be combined with the value of choice options to form a representation of expected reward. Our results provide insight into the neural processing governing the interaction between salience and value and the formation of subjective expected reward and prediction error. This work is potentially important for identifying neural markers of abnormal sensory/value processing, as is seen in some cases of psychiatric illnesses. PMID:26400937

  20. Perceptual Salience and Reward Both Influence Feedback-Related Neural Activity Arising from Choice

    PubMed Central

    Lou, Bin; Hsu, Wha-Yin

    2015-01-01

    expected reward. Here, we use electroencephelography to identify trial-by-trial neural activity of perceived stimulus salience, showing that this activity can be combined with the value of choice options to form a representation of expected reward. Our results provide insight into the neural processing governing the interaction between salience and value and the formation of subjective expected reward and prediction error. This work is potentially important for identifying neural markers of abnormal sensory/value processing, as is seen in some cases of psychiatric illnesses. PMID:26400937

  1. Can the activities of the large scale cortical network be expressed by neural energy? A brief review.

    PubMed

    Wang, Rubin; Zhu, Yating

    2016-02-01

    This paper mainly discusses and summarize that the changes of biological energy in the brain can be expressed by the biophysical energy we constructed. Different from the electrochemical energy, the biophysical energy proposed in the paper not only can be used to simulate the activity of neurons but also be used to simulate the neural activity of large scale cortical networks, so that the scientific nature of the neural energy coding was discussed. PMID:26834857

  2. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells.

    PubMed

    Pathak, Medha M; Nourse, Jamison L; Tran, Truc; Hwe, Jennifer; Arulmoli, Janahan; Le, Dai Trang T; Bernardis, Elena; Flanagan, Lisa A; Tombola, Francesco

    2014-11-11

    Neural stem cells are multipotent cells with the ability to differentiate into neurons, astrocytes, and oligodendrocytes. Lineage specification is strongly sensitive to the mechanical properties of the cellular environment. However, molecular pathways transducing matrix mechanical cues to intracellular signaling pathways linked to lineage specification remain unclear. We found that the mechanically gated ion channel Piezo1 is expressed by brain-derived human neural stem/progenitor cells and is responsible for a mechanically induced ionic current. Piezo1 activity triggered by traction forces elicited influx of Ca(2+), a known modulator of differentiation, in a substrate-stiffness-dependent manner. Inhibition of channel activity by the pharmacological inhibitor GsMTx-4 or by siRNA-mediated Piezo1 knockdown suppressed neurogenesis and enhanced astrogenesis. Piezo1 knockdown also reduced the nuclear localization of the mechanoreactive transcriptional coactivator Yes-associated protein. We propose that the mechanically gated ion channel Piezo1 is an important determinant of mechanosensitive lineage choice in neural stem cells and may play similar roles in other multipotent stem cells. PMID:25349416

  3. A current model of neural circuitry active in forming mental images

    PubMed Central

    Brodziak, Andrzej

    2013-01-01

    My aim here is to formulate a compact, intuitively understandable model of neural circuits active in imagination that would be consistent with the current state of knowledge, but that would be simple enough to be able to use for teaching. I argue that such a model should be based on the recent idea of “concept neurons” and circuits of 2 separate loops necessary for recalling mental images and consolidation of memory traces of long-term memory. This paper discusses the role of the hippocampus and temporal lobe, emphasizing the essential importance of recurrent pathways and oscillations occurring in the upper layers of hierarchical neural structures, as well as oscillations in thalamo-cortical loops. The elaborated model helps explain specific processes such as imagining future situations, novel objects, and anticipated action, as well as imagination concerning oneself, which is indispensable for the sense of identity and self-awareness. I attempt to present this compact, simple model of neural circuitry active in imagination by using some intuitive, demonstrative figures. PMID:24335907

  4. New rabies virus variants for monitoring and manipulating activity and gene expression in defined neural circuits

    PubMed Central

    Osakada, Fumitaka; Mori, Takuma; Cetin, Ali H.; Marshel, James H.; Virgen, Beatriz; Callaway, Edward M.

    2011-01-01

    SUMMARY Glycoprotein-deleted (ΔG) rabies virus is a powerful tool for studies of neural circuit structure. Here we describe the development and demonstrate the utility of new resources that allow experiments directly investigating relationships between the structure and function of neural circuits. New methods and reagents allowed efficient production of twelve novel ΔG rabies variants from plasmid DNA. These new rabies viruses express useful neuroscience tools, including: the Ca++ indicator GCaMP3, for monitoring activity; Channelrhodopsin-2, for photoactivation; allatostatin receptor, for inactivation by ligand application; rtTA, ERT2CreERT2, or FLPo, for control of gene expression. These new tools allow neurons targeted based on their connectivity, to have their function assayed or their activity or gene expression manipulated. Combining these tools with in vivo imaging and optogenetic methods, and/or inducible gene expression in transgenic mice, will facilitate experiments investigating neural circuit development, plasticity, and function that have not been possible with existing reagents. PMID:21867879

  5. Programmable active pixel sensor to investigate neural interactions within the retina

    NASA Astrophysics Data System (ADS)

    Hart, Matthew D.; Prydderch, Mark L.; Morrison, James D.; Murdoch, Derek; Mathieson, Keith

    2009-05-01

    Detection of the visual scene by the eye and the resultant neural interactions of the retina-brain system give us our perception of sight. We have developed an Active Pixel Sensor (APS) to be used as a tool for both furthering understanding of these interactions via experimentation with the retina and to make developments towards a realisable retinal prosthesis. The sensor consists of 469 pixels in a hexagonal array. The pixels are interconnected by a programmable neural network to mimic lateral interactions between retinal cells. Outputs from the sensor are in the form of biphasic current pulse trains suitable to stimulate retinal cells via a biocompatible array. The APS will be described with initial characterisation and test results.

  6. Active vibration control of flexible cantilever plates using piezoelectric materials and artificial neural networks

    NASA Astrophysics Data System (ADS)

    Abdeljaber, Osama; Avci, Onur; Inman, Daniel J.

    2016-02-01

    The study presented in this paper introduces a new intelligent methodology to mitigate the vibration response of flexible cantilever plates. The use of the piezoelectric sensor/actuator pairs for active control of plates is discussed. An intelligent neural network based controller is designed to control the optimal voltage applied on the piezoelectric patches. The control technique utilizes a neurocontroller along with a Kalman Filter to compute the appropriate actuator command. The neurocontroller is trained based on an algorithm that incorporates a set of emulator neural networks which are also trained to predict the future response of the cantilever plate. Then, the neurocontroller is evaluated by comparing the uncontrolled and controlled responses under several types of dynamic excitations. It is observed that the neurocontroller reduced the vibration response of the flexible cantilever plate significantly; the results demonstrated the success and robustness of the neurocontroller independent of the type and distribution of the excitation force.

  7. Multiple aberrant hormone receptors in Cushing's syndrome.

    PubMed

    El Ghorayeb, Nada; Bourdeau, Isabelle; Lacroix, André

    2015-10-01

    The mechanisms regulating cortisol production when ACTH of pituitary origin is suppressed in primary adrenal causes of Cushing's syndrome (CS) include diverse genetic and molecular mechanisms. These can lead either to constitutive activation of the cAMP system and steroidogenesis or to its regulation exerted by the aberrant adrenal expression of several hormone receptors, particularly G-protein coupled hormone receptors (GPCR) and their ligands. Screening for aberrant expression of GPCR in bilateral macronodular adrenal hyperplasia (BMAH) and unilateral adrenal tumors of patients with overt or subclinical CS demonstrates the frequent co-expression of several receptors. Aberrant hormone receptors can also exert their activity by regulating the paracrine secretion of ACTH or other ligands for those receptors in BMAH or unilateral tumors. The aberrant expression of hormone receptors is not limited to adrenal CS but can be implicated in other endocrine tumors including primary aldosteronism and Cushing's disease. Targeted therapies to block the aberrant receptors or their ligands could become useful in the future. PMID:25971648

  8. Reconstruction of Neural Activity from EEG Data Using Dynamic Spatiotemporal Constraints.

    PubMed

    Giraldo-Suarez, E; Martinez-Vargas, J D; Castellanos-Dominguez, G

    2016-11-01

    We present a novel iterative regularized algorithm (IRA) for neural activity reconstruction that explicitly includes spatiotemporal constraints, performing a trade-off between space and time resolutions. For improving the spatial accuracy provided by electroencephalography (EEG) signals, we explore a basis set that describes the smooth, localized areas of potentially active brain regions. In turn, we enhance the time resolution by adding the Markovian assumption for brain activity estimation at each time period. Moreover, to deal with applications that have either distributed or localized neural activity, the spatiotemporal constraints are expressed through [Formula: see text] and [Formula: see text] norms, respectively. For the purpose of validation, we estimate the neural reconstruction performance in time and space separately. Experimental testing is carried out on artificial data, simulating stationary and non-stationary EEG signals. Also, validation is accomplished on two real-world databases, one holding Evoked Potentials and another with EEG data of focal epilepsy. Moreover, responses of functional magnetic resonance imaging for the former EEG data have been measured in advance, allowing to contrast our findings. Obtained results show that the [Formula: see text]-based IRA produces a spatial resolution that is comparable to the one achieved by some widely used sparse-based estimators of brain activity. At the same time, the [Formula: see text]-based IRA outperforms other similar smooth solutions, providing a spatial resolution that is lower than the sparse [Formula: see text]-based solution. As a result, the proposed IRA is a promising method for improving the accuracy of brain activity reconstruction. PMID:27354190

  9. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children.

    PubMed

    Jasińska, Kaja K; Molfese, Peter J; Kornilov, Sergey A; Mencl, W Einar; Frost, Stephen J; Lee, Maria; Pugh, Kenneth R; Grigorenko, Elena L; Landi, Nicole

    2016-01-01

    Understanding how genes impact the brain's functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children's (age 6-10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading-related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes. PMID:27551971

  10. Endogenous testosterone levels are associated with neural activity in men with schizophrenia during facial emotion processing.

    PubMed

    Ji, Ellen; Weickert, Cynthia Shannon; Lenroot, Rhoshel; Catts, Stanley V; Vercammen, Ans; White, Christopher; Gur, Raquel E; Weickert, Thomas W

    2015-06-01

    Growing evidence suggests that testosterone may play a role in the pathophysiology of schizophrenia given that testosterone has been linked to cognition and negative symptoms in schizophrenia. Here, we determine the extent to which serum testosterone levels are related to neural activity in affective processing circuitry in men with schizophrenia. Functional magnetic resonance imaging was used to measure blood-oxygen-level-dependent signal changes as 32 healthy controls and 26 people with schizophrenia performed a facial emotion identification task. Whole brain analyses were performed to determine regions of differential activity between groups during processing of angry versus non-threatening faces. A follow-up ROI analysis using a regression model in a subset of 16 healthy men and 16 men with schizophrenia was used to determine the extent to which serum testosterone levels were related to neural activity. Healthy controls displayed significantly greater activation than people with schizophrenia in the left inferior frontal gyrus (IFG). There was no significant difference in circulating testosterone levels between healthy men and men with schizophrenia. Regression analyses between activation in the IFG and circulating testosterone levels revealed a significant positive correlation in men with schizophrenia (r=.63, p=.01) and no significant relationship in healthy men. This study provides the first evidence that circulating serum testosterone levels are related to IFG activation during emotion face processing in men with schizophrenia but not in healthy men, which suggests that testosterone levels modulate neural processes relevant to facial emotion processing that may interfere with social functioning in men with schizophrenia. PMID:25796490

  11. The BDNF Val66Met Polymorphism Influences Reading Ability and Patterns of Neural Activation in Children

    PubMed Central

    Jasińska, Kaja K.; Molfese, Peter J.; Kornilov, Sergey A.; Mencl, W. Einar; Frost, Stephen J.; Lee, Maria; Pugh, Kenneth R.; Grigorenko, Elena L.; Landi, Nicole

    2016-01-01

    Understanding how genes impact the brain’s functional activation for learning and cognition during development remains limited. We asked whether a common genetic variant in the BDNF gene (the Val66Met polymorphism) modulates neural activation in the young brain during a critical period for the emergence and maturation of the neural circuitry for reading. In animal models, the bdnf variation has been shown to be associated with the structure and function of the developing brain and in humans it has been associated with multiple aspects of cognition, particularly memory, which are relevant for the development of skilled reading. Yet, little is known about the impact of the Val66Met polymorphism on functional brain activation in development, either in animal models or in humans. Here, we examined whether the BDNF Val66Met polymorphism (dbSNP rs6265) is associated with children’s (age 6–10) neural activation patterns during a reading task (n = 81) using functional magnetic resonance imaging (fMRI), genotyping, and standardized behavioral assessments of cognitive and reading development. Children homozygous for the Val allele at the SNP rs6265 of the BDNF gene outperformed Met allele carriers on reading comprehension and phonological memory, tasks that have a strong memory component. Consistent with these behavioral findings, Met allele carriers showed greater activation in reading–related brain regions including the fusiform gyrus, the left inferior frontal gyrus and left superior temporal gyrus as well as greater activation in the hippocampus during a word and pseudoword reading task. Increased engagement of memory and spoken language regions for Met allele carriers relative to Val/Val homozygotes during reading suggests that Met carriers have to exert greater effort required to retrieve phonological codes. PMID:27551971

  12. Inactivity-induced respiratory plasticity: protecting the drive to breathe in disorders that reduce respiratory neural activity.

    PubMed

    Strey, K A; Baertsch, N A; Baker-Herman, T L

    2013-11-01

    Multiple forms of plasticity are activated following reduced respiratory neural activity. For example, in ventilated rats, a central neural apnea elicits a rebound increase in phrenic and hypoglossal burst amplitude upon resumption of respiratory neural activity, forms of plasticity called inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF), respectively. Here, we provide a conceptual framework for plasticity following reduced respiratory neural activity to guide future investigations. We review mechanisms giving rise to iPMF and iHMF, present new data suggesting that inactivity-induced plasticity is observed in inspiratory intercostals (iIMF) and point out gaps in our knowledge. We then survey conditions relevant to human health characterized by reduced respiratory neural activity and discuss evidence that inactivity-induced plasticity is elicited during these conditions. Understanding the physiological impact and circumstances in which inactivity-induced respiratory plasticity is elicited may yield novel insights into the treatment of disorders characterized by reductions in respiratory neural activity. PMID:23816599

  13. Neural activity tied to reading predicts individual differences in extended-text comprehension

    PubMed Central

    Mossbridge, Julia A.; Grabowecky, Marcia; Paller, Ken A.; Suzuki, Satoru

    2013-01-01

    Reading comprehension depends on neural processes supporting the access, understanding, and storage of words over time. Examinations of the neural activity correlated with reading have contributed to our understanding of reading comprehension, especially for the comprehension of sentences and short passages. However, the neural activity associated with comprehending an extended text is not well-understood. Here we describe a current-source-density (CSD) index that predicts individual differences in the comprehension of an extended text. The index is the difference in CSD-transformed event-related potentials (ERPs) to a target word between two conditions: a comprehension condition with words from a story presented in their original order, and a scrambled condition with the same words presented in a randomized order. In both conditions participants responded to the target word, and in the comprehension condition they also tried to follow the story in preparation for a comprehension test. We reasoned that the spatiotemporal pattern of difference-CSDs would reflect comprehension-related processes beyond word-level processing. We used a pattern-classification method to identify the component of the difference-CSDs that accurately (88%) discriminated good from poor comprehenders. The critical CSD index was focused at a frontal-midline scalp site, occurred 400–500 ms after target-word onset, and was strongly correlated with comprehension performance. Behavioral data indicated that group differences in effort or motor preparation could not explain these results. Further, our CSD index appears to be distinct from the well-known P300 and N400 components, and CSD transformation seems to be crucial for distinguishing good from poor comprehenders using our experimental paradigm. Once our CSD index is fully characterized, this neural signature of individual differences in extended-text comprehension may aid the diagnosis and remediation of reading comprehension deficits. PMID

  14. Neural activity during emotion recognition after combined cognitive plus social cognitive training in schizophrenia.

    PubMed

    Hooker, Christine I; Bruce, Lori; Fisher, Melissa; Verosky, Sara C; Miyakawa, Asako; Vinogradov, Sophia

    2012-08-01

    Cognitive remediation training has been shown to improve both cognitive and social cognitive deficits in people with schizophrenia, but the mechanisms that support this behavioral improvement are largely unknown. One hypothesis is that intensive behavioral training in cognition and/or social cognition restores the underlying neural mechanisms that support targeted skills. However, there is little research on the neural effects of cognitive remediation training. This study investigated whether a 50 h (10-week) remediation intervention which included both cognitive and social cognitive training would influence neural function in regions that support social cognition. Twenty-two stable, outpatient schizophrenia participants were randomized to a treatment condition consisting of auditory-based cognitive training (AT) [Brain Fitness Program/auditory module ~60 min/day] plus social cognition training (SCT) which was focused on emotion recognition [~5-15 min per day] or a placebo condition of non-specific computer games (CG) for an equal amount of time. Pre and post intervention assessments included an fMRI task of positive and negative facial emotion recognition, and standard behavioral assessments of cognition, emotion processing, and functional outcome. There were no significant intervention-related improvements in general cognition or functional outcome. fMRI results showed the predicted group-by-time interaction. Specifically, in comparison to CG, AT+SCT participants had a greater pre-to-post intervention increase in postcentral gyrus activity during emotion recognition of both positive and negative emotions. Furthermore, among all participants, the increase in postcentral gyrus activity predicted behavioral improvement on a standardized test of emotion processing (MSCEIT: Perceiving Emotions). Results indicate that combined cognition and social cognition training impacts neural mechanisms that support social cognition skills. PMID:22695257

  15. Neural activity tied to reading predicts individual differences in extended-text comprehension.

    PubMed

    Mossbridge, Julia A; Grabowecky, Marcia; Paller, Ken A; Suzuki, Satoru

    2013-01-01

    Reading comprehension depends on neural processes supporting the access, understanding, and storage of words over time. Examinations of the neural activity correlated with reading have contributed to our understanding of reading comprehension, especially for the comprehension of sentences and short passages. However, the neural activity associated with comprehending an extended text is not well-understood. Here we describe a current-source-density (CSD) index that predicts individual differences in the comprehension of an extended text. The index is the difference in CSD-transformed event-related potentials (ERPs) to a target word between two conditions: a comprehension condition with words from a story presented in their original order, and a scrambled condition with the same words presented in a randomized order. In both conditions participants responded to the target word, and in the comprehension condition they also tried to follow the story in preparation for a comprehension test. We reasoned that the spatiotemporal pattern of difference-CSDs would reflect comprehension-related processes beyond word-level processing. We used a pattern-classification method to identify the component of the difference-CSDs that accurately (88%) discriminated good from poor comprehenders. The critical CSD index was focused at a frontal-midline scalp site, occurred 400-500 ms after target-word onset, and was strongly correlated with comprehension performance. Behavioral data indicated that group differences in effort or motor preparation could not explain these results. Further, our CSD index appears to be distinct from the well-known P300 and N400 components, and CSD transformation seems to be crucial for distinguishing good from poor comprehenders using our experimental paradigm. Once our CSD index is fully characterized, this neural signature of individual differences in extended-text comprehension may aid the diagnosis and remediation of reading comprehension deficits. PMID

  16. Using convolutional neural networks for human activity classification on micro-Doppler radar spectrograms

    NASA Astrophysics Data System (ADS)

    Jordan, Tyler S.

    2016-05-01

    This paper presents the findings of using convolutional neural networks (CNNs) to classify human activity from micro-Doppler features. An emphasis on activities involving potential security threats such as holding a gun are explored. An automotive 24 GHz radar on chip was used to collect the data and a CNN (normally applied to image classification) was trained on the resulting spectrograms. The CNN achieves an error rate of 1.65 % on classifying running vs. walking, 17.3 % error on armed walking vs. unarmed walking, and 22 % on classifying six different actions.

  17. Altered neural activation during prepotent response inhibition in breast cancer survivors treated with chemotherapy: an fMRI study.

    PubMed

    Kam, Julia W Y; Boyd, Lara A; Hsu, Chun L; Liu-Ambrose, Teresa; Handy, Todd C; Lim, Howard J; Hayden, Sherri; Campbell, Kristin L

    2016-09-01

    While impairments in executive functions have been reported in breast cancer survivors (BCS) who have undergone adjuvant chemotherapy, only a limited number of functional neuroimaging studies have associated alterations in cerebral activity with executive functions deficits in BCS. Using fMRI, the current study assessed the neural basis underlying a specific facet of executive function, namely prepotent response inhibition. 12 BCS who self-reported cognitive problems up to 3 years following cancer treatment and 12 female healthy comparisons (HC) performed the Stroop task. We compared their neural activation between the incongruent and neutral experimental conditions. Relative to the HC group, BCS showed lower blood-oxygen level dependent signal in several frontal regions, including the anterior cingulate cortex, a region critical for response inhibition. Our data indicates reduced neural activation in BCS during a prepotent response inhibition task, providing support for the prevailing notion of neural alterations observed in BCS treated with chemotherapy. PMID:26489975

  18. Thinking about the thoughts of others; temporal and spatial neural activation during false belief reasoning.

    PubMed

    Mossad, Sarah I; AuCoin-Power, Michelle; Urbain, Charline; Smith, Mary Lou; Pang, Elizabeth W; Taylor, Margot J

    2016-07-01

    Theory of Mind (ToM) is the ability to understand the perspectives, mental states and beliefs of others in order to anticipate their behaviour and is therefore crucial to social interactions. Although fMRI has been widely used to establish the neural networks implicated in ToM, little is known about the timing of ToM-related brain activity. We used magnetoencephalography (MEG) to measure the neural processes underlying ToM, as MEG provides very accurate timing and excellent spatial localization of brain processes. We recorded MEG activity during a false belief task, a reliable measure of ToM, in twenty young adults (10 females). MEG data were recorded in a 151 sensor CTF system (MISL, Coquitlam, BC) and data were co-registered to each participant's MRI (Siemens 3T) for source reconstruction. We found stronger right temporoparietal junction (rTPJ) activations in the false belief condition from 150ms to 225ms, in the right precuneus from 275ms to 375ms, in the right inferior frontal gyrus from 200ms to 300ms and the superior frontal gyrus from 300ms to 400ms. Our findings extend the literature by demonstrating the timing and duration of neural activity in the main regions involved in the "mentalizing" network, showing that activations related to false belief in adults are predominantly right lateralized and onset around 100ms. The sensitivity of MEG will allow us to determine spatial and temporal differences in the brain processes in ToM in younger populations or those who demonstrate deficits in this ability. PMID:27039146

  19. Selective neural activation in a histologically derived model of peripheral nerve

    NASA Astrophysics Data System (ADS)

    Butson, Christopher R.; Miller, Ian O.; Normann, Richard A.; Clark, Gregory A.

    2011-06-01

    Functional electrical stimulation (FES) is a general term for therapeutic methods that use electrical stimulation to aid or replace lost ability. For FES systems that communicate with the nervous system, one critical component is the electrode interface through which the machine-body information transfer must occur. In this paper, we examine the influence of inhomogeneous tissue conductivities and positions of nodes of Ranvier on activation of myelinated axons for neuromuscular control as a function of electrode configuration. To evaluate these effects, we developed a high-resolution bioelectric model of a fascicle from a stained cross-section of cat sciatic nerve. The model was constructed by digitizing a fixed specimen of peripheral nerve, extruding the image along the axis of the nerve, and assigning each anatomical component to one of several different tissue types. Electrodes were represented by current sources in monopolar, transverse bipolar, and longitudinal bipolar configurations; neural activation was determined using coupled field-neuron simulations with myelinated axon cable models. We found that the use of an isotropic tissue medium overestimated neural activation thresholds compared with the use of physiologically based, inhomogeneous tissue medium, even after controlling for mean impedance levels. Additionally, the positions of the cathodic sources relative to the nodes of Ranvier had substantial effects on activation, and these effects were modulated by the electrode configuration. Our results indicate that physiologically based tissue properties cause considerable variability in the neural response, and the inclusion of these properties is an important component in accurately predicting activation. The results are used to suggest new electrode designs to enable selective stimulation of small diameter fibers.

  20. Touching moments: desire modulates the neural anticipation of active romantic caress

    PubMed Central

    Ebisch, Sjoerd J.; Ferri, Francesca; Gallese, Vittorio

    2014-01-01

    A romantic caress is a basic expression of affiliative behavior and a primary reinforcer. Given its inherent affective valence, its performance also would imply the prediction of reward values. For example, touching a person for whom one has strong passionate feelings likely is motivated by a strong desire for physical contact and associated with the anticipation of hedonic experiences. The present study aims at investigating how the anticipatory neural processes of active romantic caress are modulated by the intensity of the desire for affective contact as reflected by passionate feelings for the other. Functional magnetic resonance imaging scanning was performed in romantically involved partners using a paradigm that allowed to isolate the specific anticipatory representations of active romantic caress, compared with control caress, while testing for the relationship between neural activity and measures of feelings of passionate love for the other. The results demonstrated that right posterior insula activity in anticipation of romantic caress significantly co-varied with the intensity of desire for union with the other. This effect was independent of the sensory-affective properties of the performed touch, like its pleasantness. Furthermore, functional connectivity analysis showed that the same posterior insula cluster interacted with brain regions related to sensory-motor functions as well as to the processing and anticipation of reward. The findings provide insight on the neural substrate mediating between the desire for and the performance of romantic caress. In particular, we propose that anticipatory activity patterns in posterior insula may modulate subsequent sensory-affective processing of skin-to-skin contact. PMID:24616676

  1. Menstrual cycle phase does not affect sympathetic neural activity in women with postural orthostatic tachycardia syndrome

    PubMed Central

    Stickford, Abigail SL; VanGundy, Tiffany B; Levine, Benjamin D; Fu, Qi

    2015-01-01

    Abstract Patients with the postural orthostatic tachycardia syndrome (POTS) are primarily premenopausal women, which may be attributed to female sex hormones. We tested the hypothesis that hormonal fluctuations of the menstrual cycle alter sympathetic neural activity and orthostatic tolerance in POTS women. Ten POTS women were studied during the early follicular (EF) and mid-luteal (ML) phases of the menstrual cycle. Haemodynamics and muscle sympathetic nerve activity (MSNA) were measured when supine, during 60 deg upright tilt for 45 min or until presyncope, and during the cold pressor test (CPT) and Valsalva manoeuvres. Blood pressure and total peripheral resistance were higher during rest and tilting in the ML than EF phase; however, heart rate, stroke volume and cardiac output were similar between phases. There were no mean ± SD differences in MSNA burst frequency (8 ± 8 EF phase vs. 10 ± 10 bursts min–1 ML phase at rest; 34 ± 15 EF phase vs. 36 ± 16 bursts min–1 ML phase at 5 min tilt), burst incidence or total activity, nor any differences in the cardiovagal and sympathetic baroreflex sensitivities between phases under any condition. The incidence of presyncope was also the same between phases. There were no differences in haemodynamic or sympathetic responses to CPT or Valsalva. These results suggest that the menstrual cycle does not affect sympathetic neural activity but modulates blood pressure and vasoconstriction in POTS women during tilting. Thus, factors other than sympathetic neural activity are probably responsible for the symptoms of orthostatic intolerance across the menstrual cycle in women with POTS. Key points Women with the postural orthostatic tachycardia syndrome (POTS) report fluctuations in orthostatic tolerance throughout the menstrual cycle. The mechanism(s) underlying blood pressure control across the menstrual cycle in women with POTS are unknown. The findings of the present study indicate that the menstrual

  2. Interactivity and reward-related neural activation during a serious videogame.

    PubMed

    Cole, Steven W; Yoo, Daniel J; Knutson, Brian

    2012-01-01

    This study sought to determine whether playing a "serious" interactive digital game (IDG)--the Re-Mission videogame for cancer patients--activates mesolimbic neural circuits associated with incentive motivation, and if so, whether such effects stem from the participatory aspects of interactive gameplay, or from the complex sensory/perceptual engagement generated by its dynamic event-stream. Healthy undergraduates were randomized to groups in which they were scanned with functional magnetic resonance imaging (FMRI) as they either actively played Re-Mission or as they passively observed a gameplay audio-visual stream generated by a yoked active group subject. Onset of interactive game play robustly activated mesolimbic projection regions including the caudate nucleus and nucleus accumbens, as well as a subregion of the parahippocampal gyrus. During interactive gameplay, subjects showed extended activation of the thalamus, anterior insula, putamen, and motor-related regions, accompanied by decreased activation in parietal and medial prefrontal cortex. Offset of interactive gameplay activated the anterior insula and anterior cingulate. Between-group comparisons of within-subject contrasts confirmed that mesolimbic activation was significantly more pronounced in the active playgroup than in the passive exposure control group. Individual difference analyses also found the magnitude of parahippocampal activation following gameplay onset to correlate with positive attitudes toward chemotherapy assessed both at the end of the scanning session and at an unannounced one-month follow-up. These findings suggest that IDG-induced activation of reward-related mesolimbic neural circuits stems primarily from participatory engagement in gameplay (interactivity), rather than from the effects of vivid and dynamic sensory stimulation. PMID:22442733

  3. Epithelia-mesenchyme interaction plays an essential role in transdifferentiation of retinal pigment epithelium of silver mutant quail: localization of FGF and related molecules and aberrant migration pattern of neural crest cells during eye rudiment formation.

    PubMed

    Araki, Masasuke; Takano, Takako; Uemonsa, Tomoko; Nakane, Yoshifumi; Tsudzuki, Masaoki; Kaneko, Tomoko

    2002-04-15

    Homozygotes of the quail silver mutation, which have plumage color changes, also display a unique phenotype in the eye: during early embryonic development, the retinal pigment epithelium (RPE) spontaneously transdifferentiates into neural retinal tissue. Mitf is considered to be the responsible gene and to function similarly to the mouse microphthalmia mutation, and tissue interaction between RPE and surrounding mesenchymal tissue in organ culture has been shown to be essential for the initiation of the transdifferentiation process in which fibroblast growth factor (FGF) signaling is involved. The immunohistochemical results of the present study show that laminin and heparan sulfate proteoglycan, both acting as cofactors for FGF binding, are localized in the area of transdifferentiation of silver embryos much more abundantly than in wild-type embryos. More intense immunohistochemical staining with FGF-1 antibody, but not with FGF-2 antibody, is also found in the neural retina, RPE, and choroidal tissue of silver embryos than in wild-type embryos. HNK-1 immunohistochemistry revealed that clusters of HNK-1-positive cells (presumptive migrating neural crest cells) are frequently located around the developing eyes and in the posterior region of the silver embryonic eye. Finally, chick-quail chimerical eyes were made by grafting silver quail optic vesicles to chicken host embryos: in most cases, no transdifferentiation occurs in the silver RPE, but in a few cases, transdifferentiation occurs where silver quail cells predominate in the choroid tissue. These observations together with our previous in vitro study indicate that the silver mutation affects not only RPE cells but also cephalic neural crest cells, which migrate to the eye rudiment, and that these crest cells play an essential role in the transdifferentiation of RPE, possibly by modifying the FGF signaling pathway. The precise molecular mechanism involved in RPE-neural crest cell interaction is still unknown

  4. Deep Convolutional and LSTM Recurrent Neural Networks for Multimodal Wearable Activity Recognition.

    PubMed

    Ordóñez, Francisco Javier; Roggen, Daniel

    2016-01-01

    Human activity recognition (HAR) tasks have traditionally been solved using engineered features obtained by heuristic processes. Current research suggests that deep convolutional neural networks are suited to automate feature extraction from raw sensor inputs. However, human activities are made of complex sequences of motor movements, and capturing this temporal dynamics is fundamental for successful HAR. Based on the recent success of recurrent neural networks for time series domains, we propose a generic deep framework for activity recognition based on convolutional and LSTM recurrent units, which: (i) is suitable for multimodal wearable sensors; (ii) can perform sensor fusion naturally; (iii) does not require expert knowledge in designing features; and (iv) explicitly models the temporal dynamics of feature activations. We evaluate our framework on two datasets, one of which has been used in a public activity recognition challenge. Our results show that our framework outperforms competing deep non-recurrent networks on the challenge dataset by 4% on average; outperforming some of the previous reported results by up to 9%. Our results show that the framework can be applied to homogeneous sensor modalities, but can also fuse multimodal sensors to improve performance. We characterise key architectural hyperparameters' influence on performance to provide insights about their optimisation. PMID:26797612

  5. Neural activity related to cognitive and emotional empathy in post-traumatic stress disorder.

    PubMed

    Mazza, Monica; Tempesta, Daniela; Pino, Maria Chiara; Nigri, Anna; Catalucci, Alessia; Guadagni, Veronica; Gallucci, Massimo; Iaria, Giuseppe; Ferrara, Michele

    2015-04-01

    The aim of this study is to evaluate the empathic ability and its functional brain correlates in post-traumatic stress disorder subjects (PTSD). Seven PTSD subjects and ten healthy controls, all present in the L'Aquila area during the earthquake of the April 2009, underwent fMRI during which they performed a modified version of the Multifaceted Empathy Test. PTSD patients showed impairments in implicit and explicit emotional empathy, but not in cognitive empathy. Brain responses during cognitive empathy showed an increased activation in patients compared to controls in the right medial frontal gyrus and the left inferior frontal gyrus. During implicit emotional empathy responses patients with PTSD, compared to controls, exhibited greater neural activity in the left pallidum and right insula; instead the control group showed an increased activation in right inferior frontal gyrus. Finally, in the explicit emotional empathy responses the PTSD group showed a reduced neural activity in the left insula and the left inferior frontal gyrus. The behavioral deficit limited to the emotional empathy dimension, accompanied by different patterns of activation in empathy related brain structures, represent a first piece of evidence of a dissociation between emotional and cognitive empathy in PTSD patients. The present findings support the idea that empathy is a multidimensional process, with different facets depending on distinct anatomical substrates. PMID:25555525

  6. A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses.

    PubMed

    Jensen, Karin B; Kaptchuk, Ted J; Chen, Xiaoyan; Kirsch, Irving; Ingvar, Martin; Gollub, Randy L; Kong, Jian

    2015-10-01

    Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science. PMID:25452576

  7. A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses

    PubMed Central

    Jensen, Karin B.; Kaptchuk, Ted J.; Chen, Xiaoyan; Kirsch, Irving; Ingvar, Martin; Gollub, Randy L.; Kong, Jian

    2015-01-01

    Fundamental aspects of human behavior operate outside of conscious awareness. Yet, theories of conditioned responses in humans, such as placebo and nocebo effects on pain, have a strong emphasis on conscious recognition of contextual cues that trigger the response. Here, we investigated the neural pathways involved in nonconscious activation of conditioned pain responses, using functional magnetic resonance imaging in healthy participants. Nonconscious compared with conscious activation of conditioned placebo analgesia was associated with increased activation of the orbitofrontal cortex, a structure with direct connections to affective brain regions and basic reward processing. During nonconscious nocebo, there was increased activation of the thalamus, amygdala, and hippocampus. In contrast to previous assumptions about conditioning in humans, our results show that conditioned pain responses can be elicited independently of conscious awareness and our results suggest a hierarchical activation of neural pathways for nonconscious and conscious conditioned responses. Demonstrating that the human brain has a nonconscious mechanism for responding to conditioned cues has major implications for the role of associative learning in behavioral medicine and psychiatry. Our results may also open up for novel approaches to translational animal-to-human research since human consciousness and animal cognition is an inherent paradox in all behavioral science. PMID:25452576

  8. Deep Convolutional and LSTM Recurrent Neural Networks for Multimodal Wearable Activity Recognition

    PubMed Central

    Ordóñez, Francisco Javier; Roggen, Daniel

    2016-01-01

    Human activity recognition (HAR) tasks have traditionally been solved using engineered features obtained by heuristic processes. Current research suggests that deep convolutional neural networks are suited to automate feature extraction from raw sensor inputs. However, human activities are made of complex sequences of motor movements, and capturing this temporal dynamics is fundamental for successful HAR. Based on the recent success of recurrent neural networks for time series domains, we propose a generic deep framework for activity recognition based on convolutional and LSTM recurrent units, which: (i) is suitable for multimodal wearable sensors; (ii) can perform sensor fusion naturally; (iii) does not require expert knowledge in designing features; and (iv) explicitly models the temporal dynamics of feature activations. We evaluate our framework on two datasets, one of which has been used in a public activity recognition challenge. Our results show that our framework outperforms competing deep non-recurrent networks on the challenge dataset by 4% on average; outperforming some of the previous reported results by up to 9%. Our results show that the framework can be applied to homogeneous sensor modalities, but can also fuse multimodal sensors to improve performance. We characterise key architectural hyperparameters’ influence on performance to provide insights about their optimisation. PMID:26797612

  9. Human activities recognition by head movement using partial recurrent neural network

    NASA Astrophysics Data System (ADS)

    Tan, Henry C. C.; Jia, Kui; De Silva, Liyanage C.

    2003-06-01

    Traditionally, human activities recognition has been achieved mainly by the statistical pattern recognition methods or the Hidden Markov Model (HMM). In this paper, we propose a novel use of the connectionist approach for the recognition of ten simple human activities: walking, sitting down, getting up, squatting down and standing up, in both lateral and frontal views, in an office environment. By means of tracking the head movement of the subjects over consecutive frames from a database of different color image sequences, and incorporating the Elman model of the partial recurrent neural network (RNN) that learns the sequential patterns of relative change of the head location in the images, the proposed system is able to robustly classify all the ten activities performed by unseen subjects from both sexes, of different race and physique, with a recognition rate as high as 92.5%. This demonstrates the potential of employing partial RNN to recognize complex activities in the increasingly popular human-activities-based applications.

  10. Effects of Temporal Context and Temporal Expectancy on Neural Activity in Inferior Temporal Cortex

    PubMed Central

    Anderson, Britt; Sheinberg, David L.

    2008-01-01

    Timing is critical. The same event can mean different things at different times and some events are more likely to occur at one time than another. We used a cued visual classification task to evaluate how changes in temporal context affect neural responses in inferior temporal cortex, an extrastriate visual area known to be involved in object processing. On each trial a first image cued a temporal delay before a second target image appeared. The animal’s task was to classify the second image by pressing one of two buttons previously associated with that target. All images were used as both cues and targets. Whether an image cued a delay time or signaled a button press depended entirely upon whether it was the first or second picture in a trial. This paradigm allowed us to compare inferior temporal cortex neural activity to the same image subdivided by temporal context and expectation. Neuronal spiking was more robust and visually evoked local field potentials (LFP’s) larger for target presentations than for cue presentations. On invalidly cued trials, when targets appeared unexpectedly early, the magnitude of the evoked LFP was reduced and delayed and neuronal spiking was attenuated. Spike field coherence increased in the beta-gamma frequency range for expected targets. In conclusion, different neural responses in higher order ventral visual cortex may occur for the same visual image based on manipulations of temporal attention. PMID:18206961

  11. Mild blast events alter anxiety, memory, and neural activity patterns in the anterior cingulate cortex.

    PubMed

    Xie, Kun; Kuang, Hui; Tsien, Joe Z

    2013-01-01

    There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

  12. Reduction in Neural Performance following Recovery from Anoxic Stress Is Mimicked by AMPK Pathway Activation

    PubMed Central

    Money, Tomas G. A.; Sproule, Michael K. J.; Hamour, Amr F.; Robertson, R. Meldrum

    2014-01-01

    Nervous systems are energetically expensive to operate and maintain. Both synaptic and action potential signalling require a significant investment to maintain ion homeostasis. We have investigated the tuning of neural performance following a brief period of anoxia in a well-characterized visual pathway in the locust, the LGMD/DCMD looming motion-sensitive circuit. We hypothesised that the energetic cost of signalling can be dynamically modified by cellular mechanisms in response to metabolic stress. We examined whether recovery from anoxia resulted in a decrease in excitability of the electrophysiological properties in the DCMD neuron. We further examined the effect of these modifications on behavioural output. We show that recovery from anoxia affects metabolic rate, flight steering behaviour, and action potential properties. The effects of anoxia on action potentials can be mimicked by activation of the AMPK metabolic pathway. We suggest this is evidence of a coordinated cellular mechanism to reduce neural energetic demand following an anoxic stress. Together, this represents a dynamically-regulated means to link the energetic demands of neural signaling with the environmental constraints faced by the whole animal. PMID:24533112

  13. Mild Blast Events Alter Anxiety, Memory, and Neural Activity Patterns in the Anterior Cingulate Cortex

    PubMed Central

    Xie, Kun; Kuang, Hui; Tsien, Joe Z.

    2013-01-01

    There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

  14. Out-of-sync: disrupted neural activity in emotional circuitry during film viewing in melancholic depression.

    PubMed

    Guo, Christine C; Nguyen, Vinh T; Hyett, Matthew P; Parker, Gordon B; Breakspear, Michael J

    2015-01-01

    While a rich body of research in controlled experiments has established changes in the neural circuitry of emotion in major depressive disorders, little is known as to how such alterations might translate into complex, naturalistic settings--namely involving dynamic multimodal stimuli with rich contexts, such as those provided by films. Neuroimaging paradigms employing dynamic natural stimuli alleviate the anxiety often associated with complex tasks and eschew the need for laboratory-style abstractions, hence providing an ecologically valid means of elucidating neural underpinnings of neuropsychiatric disorders. To probe the neurobiological signature of refined depression subtypes, we acquired functional neuroimaging data in patients with the melancholic subtype of major depressive disorder during free viewing of emotionally salient films. We found a marked disengagement of ventromedial prefrontal cortex during natural viewing of a film with negative emotional valence in patients with melancholia. This effect significantly correlated with depression severity. Such changes occurred on the background of diminished consistency of neural activity in visual and auditory sensory networks, as well as higher-order networks involved in emotion and attention, including bilateral intraparietal sulcus and right anterior insula. These findings may reflect a failure to re-allocate resources and diminished reactivity to external emotional stimuli in melancholia. PMID:26112251

  15. Amygdala neural activity reflects spatial attention towards stimuli promising reward or threatening punishment

    PubMed Central

    Peck, Christopher J; Salzman, C Daniel

    2014-01-01

    Humans and other animals routinely identify and attend to sensory stimuli so as to rapidly acquire rewards or avoid aversive experiences. Emotional arousal, a process mediated by the amygdala, can enhance attention to stimuli in a non-spatial manner. However, amygdala neural activity was recently shown to encode spatial information about reward-predictive stimuli, and to correlate with spatial attention allocation. If representing the motivational significance of sensory stimuli within a spatial framework reflects a general principle of amygdala function, then spatially selective neural responses should also be elicited by sensory stimuli threatening aversive events. Recordings from amygdala neurons were therefore obtained while monkeys directed spatial attention towards stimuli promising reward or threatening punishment. Neural responses encoded spatial information similarly for stimuli associated with both valences of reinforcement, and responses reflected spatial attention allocation. The amygdala therefore may act to enhance spatial attention to sensory stimuli associated with rewarding or aversive experiences. DOI: http://dx.doi.org/10.7554/eLife.04478.001 PMID:25358090

  16. Reduction in neural performance following recovery from anoxic stress is mimicked by AMPK pathway activation.

    PubMed

    Money, Tomas G A; Sproule, Michael K J; Hamour, Amr F; Robertson, R Meldrum

    2014-01-01

    Nervous systems are energetically expensive to operate and maintain. Both synaptic and action potential signalling require a significant investment to maintain ion homeostasis. We have investigated the tuning of neural performance following a brief period of anoxia in a well-characterized visual pathway in the locust, the LGMD/DCMD looming motion-sensitive circuit. We hypothesised that the energetic cost of signalling can be dynamically modified by cellular mechanisms in response to metabolic stress. We examined whether recovery from anoxia resulted in a decrease in excitability of the electrophysiological properties in the DCMD neuron. We further examined the effect of these modifications on behavioural output. We show that recovery from anoxia affects metabolic rate, flight steering behaviour, and action potential properties. The effects of anoxia on action potentials can be mimicked by activation of the AMPK metabolic pathway. We suggest this is evidence of a coordinated cellular mechanism to reduce neural energetic demand following an anoxic stress. Together, this represents a dynamically-regulated means to link the energetic demands of neural signaling with the environmental constraints faced by the whole animal. PMID:24533112

  17. Out-of-sync: disrupted neural activity in emotional circuitry during film viewing in melancholic depression

    PubMed Central

    Guo, Christine C.; Nguyen, Vinh T.; Hyett, Matthew P.; Parker, Gordon B.; Breakspear, Michael J.

    2015-01-01

    While a rich body of research in controlled experiments has established changes in the neural circuitry of emotion in major depressive disorders, little is known as to how such alterations might translate into complex, naturalistic settings - namely involving dynamic multimodal stimuli with rich contexts, such as those provided by films. Neuroimaging paradigms employing dynamic natural stimuli alleviate the anxiety often associated with complex tasks and eschew the need for laboratory-style abstractions, hence providing an ecologically valid means of elucidating neural underpinnings of neuropsychiatric disorders. To probe the neurobiological signature of refined depression subtypes, we acquired functional neuroimaging data in patients with the melancholic subtype of major depressive disorder during free viewing of emotionally salient films. We found a marked disengagement of ventromedial prefrontal cortex during natural viewing of a film with negative emotional valence in patients with melancholia. This effect significantly correlated with depression severity. Such changes occurred on the background of diminished consistency of neural activity in visual and auditory sensory networks, as well as higher-order networks involved in emotion and attention, including bilateral intraparietal sulcus and right anterior insula. These findings may reflect a failure to re-allocate resources and diminished reactivity to external emotional stimuli in melancholia. PMID:26112251

  18. Neural activation during processing of aversive faces predicts treatment outcome in alcoholism.

    PubMed

    Charlet, Katrin; Schlagenhauf, Florian; Richter, Anne; Naundorf, Karina; Dornhof, Lina; Weinfurtner, Christopher E J; König, Friederike; Walaszek, Bernadeta; Schubert, Florian; Müller, Christian A; Gutwinski, Stefan; Seissinger, Annette; Schmitz, Lioba; Walter, Henrik; Beck, Anne; Gallinat, Jürgen; Kiefer, Falk; Heinz, Andreas

    2014-05-01

    Neuropsychological studies reported decoding deficits of emotional facial expressions in alcohol-dependent patients, and imaging studies revealed reduced prefrontal and limbic activation during emotional face processing. However, it remains unclear whether this reduced neural activation is mediated by alcohol-associated volume reductions and whether it interacts with treatment outcome. We combined analyses of neural activation during an aversive face-cue-comparison task and local gray matter volumes (GM) using Biological Parametric Mapping in 33 detoxified alcohol-dependent patients and 33 matched healthy controls. Alcoholics displayed reduced activation toward aversive faces-neutral shapes in bilateral fusiform gyrus [FG; Brodmann areas (BA) 18/19], right middle frontal gyrus (BA46/47), right inferior parietal gyrus (BA7) and left cerebellum compared with controls, which were explained by GM differences (except for cerebellum). Enhanced functional activation in patients versus controls was found in left rostral anterior cingulate cortex (ACC) and medial frontal gyrus (BA10/11), even after GM reduction control. Increased ACC activation correlated significantly with less (previous) lifetime alcohol intake [Lifetime Drinking History (LDH)], longer abstinence and less subsequent binge drinking in patients. High LDH appear to impair treatment outcome via its neurotoxicity on ACC integrity. Thus, high activation of the rostral ACC elicited by affective faces appears to be a resilience factor predicting better treatment outcome. Although no group differences were found, increased FG activation correlated with patients' higher LDH. Because high LDH correlated with worse task performance for facial stimuli in patients, elevated activation in the fusiform 'face' area may reflect inefficient compensatory activation. Therapeutic interventions (e.g. emotion evaluation training) may enable patients to cope with social stress and to decrease relapses after detoxification. PMID

  19. Phase locked neural activity in the human brainstem predicts preference for musical consonance

    PubMed Central

    Bones, Oliver; Hopkins, Kathryn; Krishnan, Ananthanarayan; Plack, Christopher J.

    2014-01-01

    When musical notes are combined to make a chord, the closeness of fit of the combined spectrum to a single harmonic series (the ‘harmonicity’ of the chord) predicts the perceived consonance (how pleasant and stable the chord sounds; McDermott, Lehr, & Oxenham, 2010). The distinction between consonance and dissonance is central to Western musical form. Harmonicity is represented in the temporal firing patterns of populations of brainstem neurons. The current study investigates the role of brainstem temporal coding of harmonicity in the perception of consonance. Individual preference for consonant over dissonant chords was measured using a rating scale for pairs of simultaneous notes. In order to investigate the effects of cochlear interactions, notes were presented in two ways: both notes to both ears or each note to different ears. The electrophysiological frequency following response (FFR), reflecting sustained neural activity in the brainstem synchronised to the stimulus, was also measured. When both notes were presented to both ears the perceptual distinction between consonant and dissonant chords was stronger than when the notes were presented to different ears. In the condition in which both notes were presented to the both ears additional low-frequency components, corresponding to difference tones resulting from nonlinear cochlear processing, were observable in the FFR effectively enhancing the neural harmonicity of consonant chords but not dissonant chords. Suppressing the cochlear envelope component of the FFR also suppressed the additional frequency components. This suggests that, in the case of consonant chords, difference tones generated by interactions between notes in the cochlea enhance the perception of consonance. Furthermore, individuals with a greater distinction between consonant and dissonant chords in the FFR to individual harmonics had a stronger preference for consonant over dissonant chords. Overall, the results provide compelling

  20. An Intelligent Active Video Surveillance System Based on the Integration of Virtual Neural Sensors and BDI Agents

    NASA Astrophysics Data System (ADS)

    Gregorio, Massimo De

    In this paper we present an intelligent active video surveillance system currently adopted in two different application domains: railway tunnels and outdoor storage areas. The system takes advantages of the integration of Artificial Neural Networks (ANN) and symbolic Artificial Intelligence (AI). This hybrid system is formed by virtual neural sensors (implemented as WiSARD-like systems) and BDI agents. The coupling of virtual neural sensors with symbolic reasoning for interpreting their outputs, makes this approach both very light from a computational and hardware point of view, and rather robust in performances. The system works on different scenarios and in difficult light conditions.

  1. Bioimpedance Harmonic Analysis as a Diagnostic Tool to Assess Regional Circulation and Neural Activity

    NASA Astrophysics Data System (ADS)

    Mudraya, I. S.; Revenko, S. V.; Khodyreva, L. A.; Markosyan, T. G.; Dudareva, A. A.; Ibragimov, A. R.; Romich, V. V.; Kirpatovsky, V. I.

    2013-04-01

    The novel technique based on harmonic analysis of bioimpedance microvariations with original hard- and software complex incorporating a high-resolution impedance converter was used to assess the neural activity and circulation in human urinary bladder and penis in patients with pelvic pain, erectile dysfunction, and overactive bladder. The therapeutic effects of shock wave therapy and Botulinum toxin detrusor injections were evaluated quantitatively according to the spectral peaks at low 0.1 Hz frequency (M for Mayer wave), respiratory (R) and cardiac (C) rhythms with their harmonics. Enhanced baseline regional neural activity identified according to M and R peaks was found to be presumably sympathetic in pelvic pain patients, and parasympathetic - in patients with overactive bladder. Total pulsatile activity and pulsatile resonances found in the bladder as well as in the penile spectrum characterised regional circulation and vascular tone. The abnormal spectral parameters characteristic of the patients with genitourinary diseases shifted to the norm in the cases of efficient therapy. Bioimpedance harmonic analysis seems to be a potent tool to assess regional peculiarities of circulatory and autonomic nervous activity in the course of patient treatment.

  2. Neural activation in speech production and reading aloud in native and non-native languages.

    PubMed

    Berken, Jonathan A; Gracco, Vincent L; Chen, Jen-Kai; Soles, Jennika; Watkins, Kate E; Baum, Shari; Callahan, Megan; Klein, Denise

    2015-05-15

    We used fMRI to investigate neural activation in reading aloud in bilinguals differing in age of acquisition. Three groups were compared: French-English bilinguals who acquired two languages from birth (simultaneous), French-English bilinguals who learned their L2 after the age of 5 years (sequential), and English-speaking monolinguals. While the bilingual groups contrasted in age of acquisition, they were matched for language proficiency, although sequential bilinguals produced speech with a less native-like accent in their L2 than in their L1. Simultaneous bilinguals activated similar brain regions to an equivalent degree when reading in their two languages. In contrast, sequential bilinguals more strongly activated areas related to speech-motor control and orthographic to phonological mapping, the left inferior frontal gyrus, left premotor cortex, and left fusiform gyrus, when reading aloud in L2 compared to L1. In addition, the activity in these regions showed a significant positive correlation with age of acquisition. The results provide evidence for the engagement of overlapping neural substrates for processing two languages when acquired in native context from birth. However, it appears that the maturation of certain brain regions for both speech production and phonological encoding is limited by a sensitive period for L2 acquisition regardless of language proficiency. PMID:25776210

  3. Analytically tractable studies of traveling waves of activity in integrate-and-fire neural networks

    NASA Astrophysics Data System (ADS)

    Zhang, Jie; Osan, Remus

    2016-05-01

    In contrast to other large-scale network models for propagation of electrical activity in neural tissue that have no analytical solutions for their dynamics, we show that for a specific class of integrate and fire neural networks the acceleration depends quadratically on the instantaneous speed of the activity propagation. We use this property to analytically compute the network spike dynamics and to highlight the emergence of a natural time scale for the evolution of the traveling waves. These results allow us to examine other applications of this model such as the effect that a nonconductive gap of tissue has on further activity propagation. Furthermore we show that activity propagation also depends on local conditions for other more general connectivity functions, by converting the evolution equations for network dynamics into a low-dimensional system of ordinary differential equations. This approach greatly enhances our intuition into the mechanisms of the traveling waves evolution and significantly reduces the simulation time for this class of models.

  4. Heightened Functional Neural Activation to Psychological Stress Covaries With Exaggerated Blood Pressure Reactivity

    PubMed Central

    Gianaros, Peter J.; Jennings, J. Richard; Sheu, Lei K.; Derbyshire, Stuart W.G.; Matthews, Karen A.

    2016-01-01

    Individuals who show exaggerated blood pressure reactions to psychological stressors are at increased risk for hypertension, atherosclerosis, and stroke. We tested whether individuals who show exaggerated stressor-induced blood pressure reactivity also show heightened stressor-induced neural activation in brain areas involved in controlling the cardiovascular system. In a functional MRI study, 46 postmenopausal women (mean age: 68.04; SD: 1.35 years) performed a standardized Stroop color-word interference task that served as a stressor to increase blood pressure. Across individuals, a larger task-induced rise in blood pressure covaried with heightened and correlated patterns of activation in brain areas implicated previously in stress-related cardiovascular control: the perigenual and posterior cingulate cortex, bilateral prefrontal cortex, anterior insula, and cerebellum. Entered as a set in hierarchical regression analyses, activation values in these brain areas uniquely predicted the magnitude of task-induced changes in systolic (ΔR2=0.54; P<0.001) and diastolic (ΔR2=0.27; P<0.05) blood pressure after statistical control for task accuracy and subjective reports of task stress. Heightened stressor-induced activation of cingulate, prefrontal, insular, and cerebellar brain areas may represent a functional neural phenotype that characterizes individuals who are prone to show exaggerated cardiovascular reactivity. PMID:17101844

  5. Tracking cortical entrainment in neural activity: auditory processes in human temporal cortex

    PubMed Central

    Thwaites, Andrew; Nimmo-Smith, Ian; Fonteneau, Elisabeth; Patterson, Roy D.; Buttery, Paula; Marslen-Wilson, William D.

    2015-01-01

    A primary objective for cognitive neuroscience is to identify how features of the sensory environment are encoded in neural activity. Current auditory models of loudness perception can be used to make detailed predictions about the neural activity of the cortex as an individual listens to speech. We used two such models (loudness-sones and loudness-phons), varying in their psychophysiological realism, to predict the instantaneous loudness contours produced by 480 isolated words. These two sets of 480 contours were used to search for electrophysiological evidence of loudness processing in whole-brain recordings of electro- and magneto-encephalographic (EMEG) activity, recorded while subjects listened to the words. The technique identified a bilateral sequence of loudness processes, predicted by the more realistic loudness-sones model, that begin in auditory cortex at ~80 ms and subsequently reappear, tracking progressively down the superior temporal sulcus (STS) at lags from 230 to 330 ms. The technique was then extended to search for regions sensitive to the fundamental frequency (F0) of the voiced parts of the speech. It identified a bilateral F0 process in auditory cortex at a lag of ~90 ms, which was not followed by activity in STS. The results suggest that loudness information is being used to guide the analysis of the speech stream as it proceeds beyond auditory cortex down STS toward the temporal pole. PMID:25713530

  6. Analytically tractable studies of traveling waves of activity in integrate-and-fire neural networks.

    PubMed

    Zhang, Jie; Osan, Remus

    2016-05-01

    In contrast to other large-scale network models for propagation of electrical activity in neural tissue that have no analytical solutions for their dynamics, we show that for a specific class of integrate and fire neural networks the acceleration depends quadratically on the instantaneous speed of the activity propagation. We use this property to analytically compute the network spike dynamics and to highlight the emergence of a natural time scale for the evolution of the traveling waves. These results allow us to examine other applications of this model such as the effect that a nonconductive gap of tissue has on further activity propagation. Furthermore we show that activity propagation also depends on local conditions for other more general connectivity functions, by converting the evolution equations for network dynamics into a low-dimensional system of ordinary differential equations. This approach greatly enhances our intuition into the mechanisms of the traveling waves evolution and significantly reduces the simulation time for this class of models. PMID:27300901

  7. Right hemisphere neural activations in the recall of waking fantasies and of dreams.

    PubMed

    Benedetti, Francesco; Poletti, Sara; Radaelli, Daniele; Ranieri, Rebecca; Genduso, Valeria; Cavallotti, Simone; Castelnovo, Anna; Smeraldi, Enrico; Scarone, Silvio; D'Agostino, Armando

    2015-10-01

    The story-like organization of dreams is characterized by a pervasive bizarreness of events and actions that resembles psychotic thought, and largely exceeds that observed in normal waking fantasies. Little is known about the neural correlates of the confabulatory narrative construction of dreams. In this study, dreams, fantasies elicited by ambiguous pictorial stimuli, and non-imaginative first- and third-person narratives from healthy participants were recorded, and were then studied for brain blood oxygen level-dependent functional magnetic resonance imaging on a 3.0-Tesla scanner while listening to their own narrative reports and attempting a retrieval of the corresponding experience. In respect to non-bizarre reports of daytime activities, the script-driven recall of dreams and fantasies differentially activated a right hemisphere network including areas in the inferior frontal gyrus, and superior and middle temporal gyrus. Neural responses were significantly greater for fantasies than for dreams in all regions, and inversely proportional to the degree of bizarreness observed in narrative reports. The inferior frontal gyrus, superior and middle temporal gyrus have been implicated in the semantic activation, integration and selection needed to build a coherent story representation and to resolve semantic ambiguities; in deductive and inferential reasoning; in self- and other-perspective taking, theory of mind, moral and autobiographical reasoning. Their degree of activation could parallel the level of logical robustness or inconsistency experienced when integrating information and mental representations in the process of building fantasy and dream narratives. PMID:25871325

  8. Emergence of spatially heterogeneous burst suppression in a neural field model of electrocortical activity

    PubMed Central

    Bojak, Ingo; Stoyanov, Zhivko V.; Liley, David T. J.

    2015-01-01

    Burst suppression in the electroencephalogram (EEG) is a well-described phenomenon that occurs during deep anesthesia, as well as in a variety of congenital and acquired brain insults. Classically it is thought of as spatially synchronous, quasi-periodic bursts of high amplitude EEG separated by low amplitude activity. However, its characterization as a “global brain state” has been challenged by recent results obtained with intracranial electrocortigraphy. Not only does it appear that burst suppression activity is highly asynchronous across cortex, but also that it may occur in isolated regions of circumscribed spatial extent. Here we outline a realistic neural field model for burst suppression by adding a slow process of synaptic resource depletion and recovery, which is able to reproduce qualitatively the empirically observed features during general anesthesia at the whole cortex level. Simulations reveal heterogeneous bursting over the model cortex and complex spatiotemporal dynamics during simulated anesthetic action, and provide forward predictions of neuroimaging signals for subsequent empirical comparisons and more detailed characterization. Because burst suppression corresponds to a dynamical end-point of brain activity, theoretically accounting for its spatiotemporal emergence will vitally contribute to efforts aimed at clarifying whether a common physiological trajectory is induced by the actions of general anesthetic agents. We have taken a first step in this direction by showing that a neural field model can qualitatively match recent experimental data that indicate spatial differentiation of burst suppression activity across cortex. PMID:25767438

  9. Forecast and restoration of geomagnetic activity indices by using the software-computational neural network complex

    NASA Astrophysics Data System (ADS)

    Barkhatov, Nikolay; Revunov, Sergey

    2010-05-01

    It is known that currently used indices of geomagnetic activity to some extent reflect the physical processes occurring in the interaction of the perturbed solar wind with Earth's magnetosphere. Therefore, they are connected to each other and with the parameters of near-Earth space. The establishment of such nonlinear connections is interest. For such purposes when the physical problem is complex or has many parameters the technology of artificial neural networks is applied. Such approach for development of the automated forecast and restoration method of geomagnetic activity indices with the establishment of creative software-computational neural network complex is used. Each neural network experiments were carried out at this complex aims to search for a specific nonlinear relation between the analyzed indices and parameters. At the core of the algorithm work program a complex scheme of the functioning of artificial neural networks (ANN) of different types is contained: back propagation Elman network, feed forward network, fuzzy logic network and Kohonen layer classification network. Tools of the main window of the complex (the application) the settings used by neural networks allow you to change: the number of hidden layers, the number of neurons in the layer, the input and target data, the number of cycles of training. Process and the quality of training the ANN is a dynamic plot of changing training error. Plot of comparison of network response with the test sequence is result of the network training. The last-trained neural network with established nonlinear connection for repeated numerical experiments can be run. At the same time additional training is not executed and the previously trained network as a filter input parameters get through and output parameters with the test event are compared. At statement of the large number of different experiments provided the ability to run the program in a "batch" mode is stipulated. For this purpose the user a

  10. Imaging Neural Activity Using Thy1-GCaMP Transgenic mice

    PubMed Central

    Chen, Qian; Cichon, Joseph; Wang, Wenting; Qiu, Li; Lee, Seok-Jin R.; Campbell, Nolan R.; DeStefino, Nicholas; Goard, Michael J.; Fu, Zhanyan; Yasuda, Ryohei; Looger, Loren L.; Arenkiel, Benjamin R.; Gan, Wen-Biao; Feng, Guoping

    2014-01-01

    Summary The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain, and will greatly facilitate dissecting complex structural and functional relationships of neural networks. PMID:23083733

  11. Social status alters defeat-induced neural activation in Syrian hamsters

    PubMed Central

    Morrison, Kathleen E.; Curry, Daniel W.; Cooper, Matthew A.

    2012-01-01

    While exposure to social stress leads to increased depression-like and anxiety-like behavior, some individuals are more vulnerable than others to these stress-induced changes in behavior. Prior social experience is one factor that can modulate how individuals respond to stressful events. In this study we investigated whether experience-dependent resistance to the behavioral consequences of social defeat was associated with a specific pattern of neural activation. We paired weight-matched male Syrian hamsters in daily aggressive encounters for two weeks, during which they formed a stable dominance relationship. We also included controls that were exposed to an empty cage each day for two weeks. Twenty-four hours after the final pairing or empty cage exposure, half of the subjects were socially defeated in 3, 5-min encounters, while the others were not socially defeated. Twenty-four hours after social defeat, animals were tested for conditioned defeat in a 5-min social interaction test with a non-aggressive intruder. We collected brains following social defeat and processed tissue for c-Fos immunoreactivity. We found that dominants were more likely to counter-attack the resident aggressor during social defeat than were subordinates, and they showed less submissive and defensive behavior at conditioned defeat testing compared to subordinates. Also, social status was associated with distinct patterns of defeat-induced neural activation in select brain regions including the amygdala, prefrontal cortex, hypothalamus, and lateral septum. Our results indicate that social status is an important form of prior experience that predicts both initial coping style and the degree of resistance to social defeat. Further, the differences in defeat-induced neural activation suggest possible brain regions that may control resistance to conditioned defeat in dominant individuals. PMID:22433296

  12. Predicting variations of perceptual performance across individuals from neural activity using pattern classifiers.

    PubMed

    Das, Koel; Giesbrecht, Barry; Eckstein, Miguel P

    2010-07-15

    Within the past decade computational approaches adopted from the field of machine learning have provided neuroscientists with powerful new tools for analyzing neural data. For instance, previous studies have applied pattern classification algorithms to electroencephalography data to predict the category of presented visual stimuli, human observer decision choices and task difficulty. Here, we quantitatively compare the ability of pattern classifiers and three ERP metrics (peak amplitude, mean amplitude, and onset latency of the face-selective N170) to predict variations across individuals' behavioral performance in a difficult perceptual task identifying images of faces and cars embedded in noise. We investigate three different pattern classifiers (Classwise Principal Component Analysis, CPCA; Linear Discriminant Analysis, LDA; and Support Vector Machine, SVM), five training methods differing in the selection of training data sets and three analyses procedures for the ERP measures. We show that all three pattern classifier algorithms surpass traditional ERP measurements in their ability to predict individual differences in performance. Although the differences across pattern classifiers were not large, the CPCA method with training data sets restricted to EEG activity for trials in which observers expressed high confidence about their decisions performed the highest at predicting perceptual performance of observers. We also show that the neural activity predicting the performance across individuals was distributed through time starting at 120ms, and unlike the face-selective ERP response, sustained for more than 400ms after stimulus presentation, indicating that both early and late components contain information correlated with observers' behavioral performance. Together, our results further demonstrate the potential of pattern classifiers compared to more traditional ERP techniques as an analysis tool for modeling spatiotemporal dynamics of the human brain and

  13. Sex Differences in Neural Activation to Facial Expressions Denoting Contempt and Disgust

    PubMed Central

    Aleman, André; Swart, Marte

    2008-01-01

    The facial expression of contempt has been regarded to communicate feelings of moral superiority. Contempt is an emotion that is closely related to disgust, but in contrast to disgust, contempt is inherently interpersonal and hierarchical. The aim of this study was twofold. First, to investigate the hypothesis of preferential amygdala responses to contempt expressions versus disgust. Second, to investigate whether, at a neural level, men would respond stronger to biological signals of interpersonal superiority (e.g., contempt) than women. We performed an experiment using functional magnetic resonance imaging (fMRI), in which participants watched facial expressions of contempt and disgust in addition to neutral expressions. The faces were presented as distractors in an oddball task in which participants had to react to one target face. Facial expressions of contempt and disgust activated a network of brain regions, including prefrontal areas (superior, middle and medial prefrontal gyrus), anterior cingulate, insula, amygdala, parietal cortex, fusiform gyrus, occipital cortex, putamen and thalamus. Contemptuous faces did not elicit stronger amygdala activation than did disgusted expressions. To limit the number of statistical comparisons, we confined our analyses of sex differences to the frontal and temporal lobes. Men displayed stronger brain activation than women to facial expressions of contempt in the medial frontal gyrus, inferior frontal gyrus, and superior temporal gyrus. Conversely, women showed stronger neural responses than men to facial expressions of disgust. In addition, the effect of stimulus sex differed for men versus women. Specifically, women showed stronger responses to male contemptuous faces (as compared to female expressions), in the insula and middle frontal gyrus. Contempt has been conceptualized as signaling perceived moral violations of social hierarchy, whereas disgust would signal violations of physical purity. Thus, our results suggest a

  14. A multichannel integrated circuit for electrical recording of neural activity, with independent channel programmability.

    PubMed

    Mora Lopez, Carolina; Prodanov, Dimiter; Braeken, Dries; Gligorijevic, Ivan; Eberle, Wolfgang; Bartic, Carmen; Puers, Robert; Gielen, Georges

    2012-04-01

    Since a few decades, micro-fabricated neural probes are being used, together with microelectronic interfaces, to get more insight in the activity of neuronal networks. The need for higher temporal and spatial recording resolutions imposes new challenges on the design of integrated neural interfaces with respect to power consumption, data handling and versatility. In this paper, we present an integrated acquisition system for in vitro and in vivo recording of neural activity. The ASIC consists of 16 low-noise, fully-differential input channels with independent programmability of its amplification (from 100 to 6000 V/V) and filtering (1-6000 Hz range) capabilities. Each channel is AC-coupled and implements a fourth-order band-pass filter in order to steeply attenuate out-of-band noise and DC input offsets. The system achieves an input-referred noise density of 37 nV/√Hz, a NEF of 5.1, a CMRR > 60 dB, a THD < 1% and a sampling rate of 30 kS/s per channel, while consuming a maximum of 70 μA per channel from a single 3.3 V. The ASIC was implemented in a 0.35 μm CMOS technology and has a total area of 5.6 × 4.5 mm². The recording system was successfully validated in in vitro and in vivo experiments, achieving simultaneous multichannel recordings of cell activity with satisfactory signal-to-noise ratios. PMID:23852975

  15. Gaussian-Process Factor Analysis for Low-Dimensional Single-Trial Analysis of Neural Population Activity

    PubMed Central

    Yu, Byron M.; Cunningham, John P.; Santhanam, Gopal; Ryu, Stephen I.; Shenoy, Krishna V.; Sahani, Maneesh

    2009-01-01

    We consider the problem of extracting smooth, low-dimensional neural trajectories that summarize the activity recorded simultaneously from many neurons on individual experimental trials. Beyond the benefit of visualizing the high-dimensional, noisy spiking activity in a compact form, such trajectories can offer insight into the dynamics of the neural circuitry underlying the recorded activity. Current methods for extracting neural trajectories involve a two-stage process: the spike trains are first smoothed over time, then a static dimensionality-reduction technique is applied. We first describe extensions of the two-stage methods that allow the degree of smoothing to be chosen in a principled way and that account for spiking variability, which may vary both across neurons and across time. We then present a novel method for extracting neural trajectories—Gaussian-process factor analysis (GPFA)—which unifies the smoothing and dimensionality-reduction operations in a common probabilistic framework. We applied these methods to the activity of 61 neurons recorded simultaneously in macaque premotor and motor cortices during reach planning and execution. By adopting a goodness-of-fit metric that measures how well the activity of each neuron can be predicted by all other recorded neurons, we found that the proposed extensions improved the predictive ability of the two-stage methods. The predictive ability was further improved by going to GPFA. From the extracted trajectories, we directly observed a convergence in neural state during motor planning, an effect that was shown indirectly by previous studies. We then show how such methods can be a powerful tool for relating the spiking activity across a neural population to the subject's behavior on a single-trial basis. Finally, to assess how well the proposed methods characterize neural population activity when the underlying time course is known, we performed simulations that revealed that GPFA performed tens of percent

  16. Neural activity in the suprachiasmatic circadian clock of nocturnal mice anticipating a daytime meal.

    PubMed

    Dattolo, T; Coomans, C P; van Diepen, H C; Patton, D F; Power, S; Antle, M C; Meijer, J H; Mistlberger, R E

    2016-02-19

    Circadian rhythms in mammals are regulated by a system of circadian oscillators that includes a light-entrainable pacemaker in the suprachiasmatic nucleus (SCN) and food-entrainable oscillators (FEOs) elsewhere in the brain and body. In nocturnal rodents, the SCN promotes sleep in the day and wake at night, while FEOs promote an active state in anticipation of a predictable daily meal. For nocturnal animals to anticipate a daytime meal, wake-promoting signals from FEOs must compete with sleep-promoting signals from the SCN pacemaker. One hypothesis is that FEOs impose a daily rhythm of inhibition on SCN output that is timed to permit the expression of activity prior to a daytime meal. This hypothesis predicts that SCN activity should decrease prior to the onset of anticipatory activity and remain suppressed through the scheduled mealtime. To assess the hypothesis, neural activity in the SCN of mice anticipating a 4-5-h daily meal in the light period was measured using FOS immunohistochemistry and in vivo multiple unit electrophysiology. SCN FOS, quantified by optical density, was significantly reduced at the expected mealtime in food-anticipating mice with access to a running disk, compared to ad libitum-fed and acutely fasted controls. Group differences were not significant when FOS was quantified by other methods, or in mice without running disks. SCN electrical activity was markedly decreased during locomotion in some mice but increased in others. Changes in either direction were concurrent with locomotion, were not specific to food anticipation, and were not sustained during longer pauses. Reduced FOS indicates a net suppression of SCN activity that may depend on the intensity or duration of locomotion. The timing of changes in SCN activity relative to locomotion suggests that any effect of FEOs on SCN output is mediated indirectly, by feedback from neural or systemic correlates of locomotion. PMID:26701294

  17. Integration of Optical Manipulation and Electrophysiological Tools to Modulate and Record Activity in Neural Networks

    NASA Astrophysics Data System (ADS)

    Difato, F.; Schibalsky, L.; Benfenati, F.; Blau, A.

    2011-07-01

    We present an optical system that combines IR (1064 nm) holographic optical tweezers with a sub-nanosecond-pulsed UV (355 nm) laser microdissector for the optical manipulation of single neurons and entire networks both on transparent and non-transparent substrates in vitro. The phase-modulated laser beam can illuminate the sample concurrently or independently from above or below assuring compatibility with different types of microelectrode array and patch-clamp electrophysiology. By combining electrophysiological and optical tools, neural activity in response to localized stimuli or injury can be studied and quantified at sub-cellular, cellular, and network level.

  18. Relations among pure-tone sound stimuli, neural activity, and the loudness sensation

    NASA Technical Reports Server (NTRS)

    Howes, W. L.

    1972-01-01

    Both the physiological and psychological responses to pure-tone sound stimuli are used to derive formulas which: (1) relate the loudness, loudness level, and sound-pressure level of pure tones; (2) apply continuously over most of the acoustic regime, including the loudness threshold; and (3) contain no undetermined coefficients. Some of the formulas are fundamental for calculating the loudness of any sound. Power-law formulas relating the pure-tone sound stimulus, neural activity, and loudness are derived from published data.

  19. Fluctuations in nuclear envelope's potential mediate synchronization of early neural activity.

    PubMed

    Yamashita, Masayuki

    2011-03-01

    Neural progenitor cells and developing neurons show periodic, synchronous Ca(2+) rises even before synapse formation, and the origin of the synchronous activity remains unknown. Here, fluorescence measurement revealed that the membrane potential of the nuclear envelope, which forms an intracellular Ca(2+) store, changed with a release of Ca(2+) and generated spontaneous, periodic bursts of fluctuations in potential. Furthermore, changes in the nuclear envelope's potential underlay spike burst generations. These results support the model that voltage fluctuations of the nuclear envelope synchronize Ca(2+) release between cells and also function as a current noise generator to cause synchronous burst discharges. PMID:21296053

  20. Triphasic spike-timing-dependent plasticity organizes networks to produce robust sequences of neural activity

    PubMed Central

    Waddington, Amelia; Appleby, Peter A.; De Kamps, Marc; Cohen, Netta

    2012-01-01

    Synfire chains have long been proposed to generate precisely timed sequences of neural activity. Such activity has been linked to numerous neural functions including sensory encoding, cognitive and motor responses. In particular, it has been argued that synfire chains underlie the precise spatiotemporal firing patterns that control song production in a variety of songbirds. Previous studies have suggested that the development of synfire chains requires either initial sparse connectivity or strong topological constraints, in addition to any synaptic learning rules. Here, we show that this necessity can be removed by using a previously reported but hitherto unconsidered spike-timing-dependent plasticity (STDP) rule and activity-dependent excitability. Under this rule the network develops stable synfire chains that possess a non-trivial, scalable multi-layer structure, in which relative layer sizes appear to follow a universal function. Using computational modeling and a coarse grained random walk model, we demonstrate the role of the STDP rule in growing, molding and stabilizing the chain, and link model parameters to the resulting structure. PMID:23162457

  1. Shaping prestimulus neural activity with auditory rhythmic stimulation improves the temporal allocation of attention.

    PubMed

    Ronconi, Luca; Pincham, Hannah L; Cristoforetti, Giulia; Facoetti, Andrea; Szűcs, Dénes

    2016-05-01

    Human attention fluctuates across time, and even when stimuli have identical physical characteristics and the task demands are the same, relevant information is sometimes consciously perceived and at other times not. A typical example of this phenomenon is the attentional blink, where participants show a robust deficit in reporting the second of two targets (T2) in a rapid serial visual presentation (RSVP) stream. Previous electroencephalographical (EEG) studies showed that neural correlates of correct T2 report are not limited to the RSVP period, but extend before visual stimulation begins. In particular, reduced oscillatory neural activity in the alpha band (8-12 Hz) before the onset of the RSVP has been linked to lower T2 accuracy. We therefore examined whether auditory rhythmic stimuli presented at a rate of 10 Hz (within the alpha band) could increase oscillatory alpha-band activity and improve T2 performance in the attentional blink time window. Behaviourally, the auditory rhythmic stimulation worked to enhance T2 accuracy. This enhanced perception was associated with increases in the posterior T2-evoked N2 component of the event-related potentials and this effect was observed selectively at lag 3. Frontal and posterior oscillatory alpha-band activity was also enhanced during auditory stimulation in the pre-RSVP period and positively correlated with T2 accuracy. These findings suggest that ongoing fluctuations can be shaped by sensorial events to improve the allocation of attention in time. PMID:26986506

  2. Artificial neural network and multiple regression model for nickel(II) adsorption on powdered activated carbons.

    PubMed

    Hema, M; Srinivasan, K

    2011-07-01

    Nickel removal efficiency of powered activated carbons of coconut oilcake, neem oilcake and commercial carbon was investigated by using artificial neural network. The effective parameters for the removal of nickel (%R) by adsorption process, which included the pH, contact time (T), distinctiveness of activated carbon (Cn), amount of activated carbon (Cw) and initial concentration of nickel (Co) were investigated. Levenberg-Marquardt (LM) Back-propagation algorithm is used to train the network. The network topology was optimized by varying number of hidden layer and number of neurons in hidden layer. The model was developed in terms of training; validation and testing of experimental data, the test subsets that each of them contains 60%, 20% and 20% of total experimental data, respectively. Multiple regression equation was developed for nickel adsorption system and the output was compared with both simulated and experimental outputs. Standard deviation (SD) with respect to experimental output was quite higher in the case of regression model when compared with ANN model. The obtained experimental data best fitted with the artificial neural network. PMID:23029923

  3. Optical Recording of Suprathreshold Neural Activity with Single-cell and Single-spike Resolution

    PubMed Central

    Ranganathan, Gayathri Nattar; Koester, Helmut J.

    2012-01-01

    Signaling of information in the vertebrate central nervous system is often carried by populations of neurons rather than individual neurons. Also propagation of suprathreshold spiking activity involves populations of neurons. Empirical studies addressing cortical function directly thus require recordings from populations of neurons with high resolution. Here we describe an optical method and a deconvolution algorithm to record neural activity from up to 100 neurons with single-cell and single-spike resolution. This method relies on detection of the transient increases in intracellular somatic calcium concentration associated with suprathreshold electrical spikes (action potentials) in cortical neurons. High temporal resolution of the optical recordings is achieved by a fast random-access scanning technique using acousto-optical deflectors (AODs)1. Two-photon excitation of the calcium-sensitive dye results in high spatial resolution in opaque brain tissue2. Reconstruction of spikes from the fluorescence calcium recordings is achieved by a maximum-likelihood method. Simultaneous electrophysiological and optical recordings indicate that our method reliably detects spikes (>97% spike detection efficiency), has a low rate of false positive spike detection (< 0.003 spikes/sec), and a high temporal precision (about 3 msec) 3. This optical method of spike detection can be used to record neural activity in vitro and in anesthetized animals in vivo3,4. PMID:22972033

  4. Temporal-Spatial Neural Activation Patterns Linked to Perceptual Encoding of Emotional Salience

    PubMed Central

    Todd, Rebecca M.; Taylor, Margot J.; Robertson, Amanda; Cassel, Daniel B.; Doesberg, Sam M.; Lee, Daniel H.; Shek, Pang N.; Pang, Elizabeth W.

    2014-01-01

    It is well known that we continuously filter incoming sensory information, selectively allocating attention to what is important while suppressing distracting or irrelevant information. Yet questions remain about spatiotemporal patterns of neural processes underlying attentional biases toward emotionally significant aspects of the world. One index of affectively biased attention is an emotional variant of an attentional blink (AB) paradigm, which reveals enhanced perceptual encoding for emotionally salient over neutral stimuli under conditions of limited executive attention. The present study took advantage of the high spatial and temporal resolution of magnetoencephalography (MEG) to investigate neural activation related to emotional and neutral targets in an AB task. MEG data were collected while participants performed a rapid stimulus visual presentation task in which two target stimuli were embedded in a stream of distractor words. The first target (T1) was a number and the second (T2) either an emotionally salient or neutral word. Behavioural results replicated previous findings of greater accuracy for emotionally salient than neutral T2 words. MEG source analyses showed that activation in orbitofrontal cortex, characterized by greater power in the theta and alpha bands, and dorsolateral prefrontal activation were associated with successful perceptual encoding of emotionally salient relative to neutral words. These effects were observed between 250 and 550 ms, latencies associated with discrimination of perceived from unperceived stimuli. These data suggest that important nodes of both emotional salience and frontoparietal executive systems are associated with the emotional modulation of the attentional blink. PMID:24727751

  5. Dynamic reorganization of neural activity in motor cortex during new sequence production.

    PubMed

    Lu, Xiaofeng; Ashe, James

    2015-09-01

    Although previous studies have shown that primary motor cortex (M1) neurons are modulated during the performance of a sequence of movements, it is not known how this neural activity in the M1 reorganizes during new learning of sequence-dependent motor skills. Here we trained monkeys to move to each of four spatial targets to produce multiple distinct sequences of movements in which the spatial organization of the targets determined uniquely the serial order of the movements. After the monkeys memorized the sequences, we changed one element of these over-practised sequences and the subjects were required to learn the new sequence through trial and error. When one element in an over-learned four-element sequence was changed, the sequence-specific neural activity was totally disrupted, but relatively minor changes in the direction-specific activity were observed. The data suggest that sequential motor skills are represented within M1 in the context of the complete sequential behavior rather than as a series of single consecutive movements; and sequence-specific neurons in the M1 are involved in new learning of sequence by using memorized knowledge to acquire complex motor skill efficiently. PMID:26202600

  6. Social Exclusion in Middle Childhood: Rejection Events, Slow-wave Neural Activity and Ostracism Distress

    PubMed Central

    Crowley, Michael J.; Wu, Jia; Molfese, Peter J.; Mayes, Linda C.

    2010-01-01

    This study examined neural activity with event-related potentials (ERPs) in middle childhood during a computer-simulated ball-toss game, Cyberball. Experiencing fair play initially, children were ultimately excluded by the other players. We focused specifically on “not my turn” events within fair play and rejection events within social exclusion. Dense-array ERPs revealed that rejection events are perceived rapidly. Condition differences (“not my turn” vs. rejection) were evident in a posterior ERP peaking at 420 ms consistent, with a larger P3 effect for rejection events indicating that in middle childhood rejection events are differentiated in < 500 ms. Condition differences were evident for slow-wave activity (500–900 ms) in the medial frontal cortical region and the posterior occipital-parietal region, with rejection events more negative frontally and more positive posteriorly. Distress from the rejection experience was associated with a more negative frontal slow wave and a larger late positive slow wave, but only for rejection events. Source modeling with Geosouce software suggested that slow wave neural activity in cortical regions previously identified in functional imaging studies of ostracism, including subgenual cortex, ventral anterior cingulate cortex and insula was greater for rejection events vs. “not my turn” events. PMID:20628967

  7. Co-speech gestures influence neural activity in brain regions associated with processing semantic information.

    PubMed

    Dick, Anthony Steven; Goldin-Meadow, Susan; Hasson, Uri; Skipper, Jeremy I; Small, Steven L

    2009-11-01

    Everyday communication is accompanied by visual information from several sources, including co-speech gestures, which provide semantic information listeners use to help disambiguate the speaker's message. Using fMRI, we examined how gestures influence neural activity in brain regions associated with processing semantic information. The BOLD response was recorded while participants listened to stories under three audiovisual conditions and one auditory-only (speech alone) condition. In the first audiovisual condition, the storyteller produced gestures that naturally accompany speech. In the second, the storyteller made semantically unrelated hand movements. In the third, the storyteller kept her hands still. In addition to inferior parietal and posterior superior and middle temporal regions, bilateral posterior superior temporal sulcus and left anterior inferior frontal gyrus responded more strongly to speech when it was further accompanied by gesture, regardless of the semantic relation to speech. However, the right inferior frontal gyrus was sensitive to the semantic import of the hand movements, demonstrating more activity when hand movements were semantically unrelated to the accompanying speech. These findings show that perceiving hand movements during speech modulates the distributed pattern of neural activation involved in both biological motion perception and discourse comprehension, suggesting listeners attempt to find meaning, not only in the words speakers produce, but also in the hand movements that accompany speech. PMID:19384890

  8. Shaping prestimulus neural activity with auditory rhythmic stimulation improves the temporal allocation of attention

    PubMed Central

    Pincham, Hannah L.; Cristoforetti, Giulia; Facoetti, Andrea; Szűcs, Dénes

    2016-01-01

    Human attention fluctuates across time, and even when stimuli have identical physical characteristics and the task demands are the same, relevant information is sometimes consciously perceived and at other times not. A typical example of this phenomenon is the attentional blink, where participants show a robust deficit in reporting the second of two targets (T2) in a rapid serial visual presentation (RSVP) stream. Previous electroencephalographical (EEG) studies showed that neural correlates of correct T2 report are not limited to the RSVP period, but extend before visual stimulation begins. In particular, reduced oscillatory neural activity in the alpha band (8-12 Hz) before the onset of the RSVP has been linked to lower T2 accuracy. We therefore examined whether auditory rhythmic stimuli presented at a rate of 10 Hz (within the alpha band) could increase oscillatory alpha-band activity and improve T2 performance in the attentional blink time window. Behaviourally, the auditory rhythmic stimulation worked to enhance T2 accuracy. This enhanced perception was associated with increases in the posterior T2-evoked N2 component of the event-related potentials and this effect was observed selectively at lag 3. Frontal and posterior oscillatory alpha-band activity was also enhanced during auditory stimulation in the pre-RSVP period and positively correlated with T2 accuracy. These findings suggest that ongoing fluctuations can be shaped by sensorial events to improve the allocation of attention in time. PMID:26986506

  9. Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Phil; Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.; Black, Michael J.

    2008-12-01

    Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding. Disclosure. JPD is the Chief Scientific Officer and a director of Cyberkinetics Neurotechnology Systems (CYKN); he holds stock and receives compensation. JDS has been a consultant for CYKN. LRH receives clinical trial support from CYKN.

  10. Cognitive-affective neural plasticity following active-controlled mindfulness intervention

    PubMed Central

    Allen, Micah; Dietz, Martin; Blair, Karina S.; van Beek, Martijn; Rees, Geraint; Vestergaard-Poulsen, Peter; Lutz, Antoine; Roepstorff, Andreas

    2015-01-01

    Mindfulness meditation is a set of attention-based, regulatory and self-inquiry training regimes. Although the impact of mindfulness meditation training (MT) on self-regulation is well established, the neural mechanisms supporting such plasticity are poorly understood. MT is thought to act on attention through interoceptive salience and attentional control mechanisms, but until now conflicting evidence from behavioral and neural measures has made it difficult to distinguish the role of these mechanisms. To resolve this question we conducted a fully randomized 6-week longitudinal trial of MT, explicitly controlling for cognitive and treatment effects with an active control group. We measured behavioral metacognition and whole-brain Blood Oxygenation Level Dependent (BOLD) signals using functional MRI during an affective Stroop task before and after intervention. Although both groups improved significantly on a response-inhibition task, only the MT group showed reduced affective Stroop conflict. Moreover, the MT group displayed greater dorsolateral prefrontal cortex (DLPFC) responses during executive processing, consistent with increased recruitment of top-down mechanisms to resolve conflict. In contrast, we did not observe overall group by time interactions on negative affect-related RTs or BOLD responses. However, only participants with the greatest amount of MT practice showed improvements in response-inhibition and increased recruitment of dorsal anterior cingulate cortex (dACC), medial prefrontal cortex (mPFC), and right anterior insula during negative valence processing. Collectively our findings highlight the importance of active control in MT research, and indicate unique neural mechanisms for progressive stages of mindfulness training. PMID:23115195

  11. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis

    PubMed Central

    Knobloch, Marlen; Braun, Simon M. G.; Zurkirchen, Luis; von Schoultz, Carolin; Zamboni, Nicola; Arauzo-Bravo, Marcos J.; Kovacs, Werner J.; Karalay, Özlem; Suter, Ueli; Machado, Raquel A. C.; Roccio, Marta; Lutolf, Matthias P.; Semenkovich, Clay F.; Jessberger, Sebastian

    2013-01-01

    Mechanisms controlling the proliferative activity of neural stem and progenitor cells (NSPCs) have a pivotal role to ensure life-long neurogenesis in the mammalian brain1. How metabolic programs are coupled with NSPC activity remains unknown. Here we show that fatty acid synthase (Fasn), the key enzyme of de novo lipogenesis2, is highly active in adult NSPCs and that conditional deletion of Fasn in mouse NSPCs impairs adult neurogenesis. The rate of de novo lipid synthesis and subsequent proliferation of NSPCs is regulated by Spot14, a gene previously implicated in lipid metabolism3–5, that we found to be selectively expressed in low proliferating adult NSPCs. Spot14 reduces the availability of malonyl-CoA6, which is an essential substrate for Fasn to fuel lipogenesis. Thus, we identify here a functional coupling between the regulation of lipid metabolism and adult NSPC proliferation. PMID:23201681

  12. Spatial Patterns of Persistent Neural Activity Vary with the Behavioral Context of Short-Term Memory

    PubMed Central

    Daie, Kayvon

    2015-01-01

    Summary A short-term memory can be evoked by different inputs and control separate targets in different behavioral contexts. To address the circuit mechanisms underlying context-dependent memory function, we determined through optical imaging how memory is encoded at the whole-network level in two behavioral settings. Persistent neural activity maintaining a memory of desired eye position was imaged throughout the oculomotor integrator after saccadic or optokinetic stimulation. While eye position was encoded by the amplitude of network activity, the spatial patterns of firing were context-dependent: cells located caudally generally were most persistent following saccadic input, whereas cells located rostrally were most persistent following optokinetic input. To explain these data, we computationally identified four independent modes of network activity and found these were differentially accessed by saccadic and optokinetic inputs. These results show how a circuit can simultaneously encode memory value and behavioral context, respectively, in its amplitude and spatial pattern of persistent firing. PMID:25661184

  13. Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner

    PubMed Central

    Schafer, Dorothy P; Lehrman, Emily K; Kautzman, Amanda G; Koyama, Ryuta; Mardinly, Alan R; Yamasaki, Ryo; Ransohoff, Richard M; Greenberg, Michael E; Barres, Ben A; Stevens, Beth

    2012-01-01

    SUMMARY Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses. PMID:22632727

  14. Aberration correction of unstable resonators

    NASA Technical Reports Server (NTRS)

    Lang, Robert J. (Inventor)

    1994-01-01

    Construction of aspheric reflectors for unstable resonator lasers to provide an arbitrary laser mode inside the resonator to correct aberrations of an output beam by the construction of the shape of an end reflector opposite the output reflector of the resonator cavity, such as aberrations resulting from refraction of a beam exiting the solid of the resonator having an index of refraction greater than 1 or to produce an aberration in the output beam that will precisely compensate for the aberration of an optical train into which the resonator beam is coupled.

  15. Differences in neural activation for object-directed grasping in chimpanzees and humans.

    PubMed

    Hecht, Erin E; Murphy, Lauren E; Gutman, David A; Votaw, John R; Schuster, David M; Preuss, Todd M; Orban, Guy A; Stout, Dietrich; Parr, Lisa A

    2013-08-28

    The human faculty for object-mediated action, including tool use and imitation, exceeds that of even our closest primate relatives and is a key foundation of human cognitive and cultural uniqueness. In humans and macaques, observing object-directed grasping actions activates a network of frontal, parietal, and occipitotemporal brain regions, but differences in human and macaque activation suggest that this system has been a focus of selection in the primate lineage. To study the evolution of this system, we performed functional neuroimaging in humans' closest living relatives, chimpanzees. We compare activations during performance of an object-directed manual grasping action, observation of the same action, and observation of a mimed version of the action that consisted of only movements without results. Performance and observation of the same action activated a distributed frontoparietal network similar to that reported in macaques and humans. Like humans and unlike macaques, these regions were also activated by observing movements without results. However, in a direct chimpanzee/human comparison, we also identified unique aspects of human neural responses to observed grasping. Chimpanzee activation showed a prefrontal bias, including significantly more activity in ventrolateral prefrontal cortex, whereas human activation was more evenly distributed across more posterior regions, including significantly more activation in ventral premotor cortex, inferior parietal cortex, and inferotemporal cortex. This indicates a more "bottom-up" representation of observed action in the human brain and suggests that the evolution of tool use, social learning, and cumulative culture may have involved modifications of frontoparietal interactions. PMID:23986247

  16. Transitionality in addiction: A "temporal continuum" hypotheses involving the aberrant motivation, the hedonic dysregulation, and the aberrant learning.

    PubMed

    Patrono, Enrico; Gasbarri, Antonella; Tomaz, Carlos; Nishijo, Hisao

    2016-08-01

    Addiction is a chronic compulsion and relapsing disorder. It involves several brain areas and circuits, which encode vary functions such as reward, motivation, and memory. Drug addiction is defined as a "pathological pattern of use of a substance", characterized by the loss of control on drug-taking-related behaviors, the pursuance of those behaviors even in the presence of negative consequences, and a strong motivated activity to assume substances. Three different theories guide experimental research on drug addiction. Each of these theories consider singles features, such as an aberrant motivation, a hedonic dysregulation, and an aberrant habit learning as the main actor to explain the entire process of the addictive behaviors. The major goal of this study is to present a new hypotheses of transitionality from a controlled use to abuse of addictive substances trough the overview of the three different theories, considering all the single features of each single theory together on the same "temporal continuum" from use to abuse of addictive substances. Recently, it has been suggested that common neural systems may be activated by natural and pharmacological stimuli, raising the hypotheses that binge-eating disorders could be considered as addictive behaviors. The second goal of this study is to present evidences in order to highlight a possible psycho-bio-physiological superimposition between drug and "food addiction". Finally, interesting questions are brought up starting from last findings about a theoretical/psycho-bio-physiological superimposition between drug and "food addiction" and their possibly same transitionality along the same "temporal continuum" from use to abuse of addictive substances in order to investigate new therapeutic strategies based on new therapeutic strategies based on the individual moments characterizing the transition from the voluntary intake of substances to the maladaptive addictive behavior. PMID:27372858

  17. CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain.

    PubMed

    Wang, Jing; Weaver, Ian C G; Gauthier-Fisher, Andrée; Wang, Haoran; He, Ling; Yeomans, John; Wondisford, Frederic; Kaplan, David R; Miller, Freda D

    2010-01-19

    Increasing evidence indicates that epigenetic changes regulate cell genesis. Here, we ask about neural precursors, focusing on CREB binding protein (CBP), a histone acetyltransferase that, when haploinsufficient, causes Rubinstein-Taybi syndrome (RTS), a genetic disorder with cognitive dysfunction. We show that neonatal cbp(+/-) mice are behaviorally impaired, displaying perturbed vocalization behavior. cbp haploinsufficiency or genetic knockdown with siRNAs inhibited differentiation of embryonic cortical precursors into all three neural lineages, coincident with decreased CBP binding and histone acetylation at promoters of neuronal and glial genes. Inhibition of histone deacetylation rescued these deficits. Moreover, CBP phosphorylation by atypical protein kinase C zeta was necessary for histone acetylation at neural gene promoters and appropriate differentiation. These data support a model in which environmental cues regulate CBP activity and histone acetylation to control neural precursor competency to differentiate, and indicate that cbp haploinsufficiency disrupts this mechanism, thereby likely causing cognitive dysfunction in RTS. PMID:20152182

  18. Recovery of Dynamics and Function in Spiking Neural Networks with Closed-Loop Control

    PubMed Central

    Vlachos, Ioannis; Deniz, Taşkin; Aertsen, Ad; Kumar, Arvind

    2016-01-01

    There is a growing interest in developing novel brain stimulation methods to control disease-related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system. PMID:26829673

  19. Recovery of Dynamics and Function in Spiking Neural Networks with Closed-Loop Control.

    PubMed

    Vlachos, Ioannis; Deniz, Taşkin; Aertsen, Ad; Kumar, Arvind

    2016-02-01

    There is a growing interest in developing novel brain stimulation methods to control disease-related aberrant neural activity and to address basic neuroscience questions. Conventional methods for manipulating brain activity rely on open-loop approaches that usually lead to excessive stimulation and, crucially, do not restore the original computations performed by the network. Thus, they are often accompanied by undesired side-effects. Here, we introduce delayed feedback control (DFC), a conceptually simple but effective method, to control pathological oscillations in spiking neural networks (SNNs). Using mathematical analysis and numerical simulations we show that DFC can restore a wide range of aberrant network dynamics either by suppressing or enhancing synchronous irregular activity. Importantly, DFC, besides steering the system back to a healthy state, also recovers the computations performed by the underlying network. Finally, using our theory we identify the role of single neuron and synapse properties in determining the stability of the closed-loop system. PMID:26829673

  20. Average synaptic activity and neural networks topology: a global inverse problem

    NASA Astrophysics Data System (ADS)

    Burioni, Raffaella; Casartelli, Mario; di Volo, Matteo; Livi, Roberto; Vezzani, Alessandro

    2014-03-01

    The dynamics of neural networks is often characterized by collective behavior and quasi-synchronous events, where a large fraction of neurons fire in short time intervals, separated by uncorrelated firing activity. These global temporal signals are crucial for brain functioning. They strongly depend on the topology of the network and on the fluctuations of the connectivity. We propose a heterogeneous mean-field approach to neural dynamics on random networks, that explicitly preserves the disorder in the topology at growing network sizes, and leads to a set of self-consistent equations. Within this approach, we provide an effective description of microscopic and large scale temporal signals in a leaky integrate-and-fire model with short term plasticity, where quasi-synchronous events arise. Our equations provide a clear analytical picture of the dynamics, evidencing the contributions of both periodic (locked) and aperiodic (unlocked) neurons to the measurable average signal. In particular, we formulate and solve a global inverse problem of reconstructing the in-degree distribution from the knowledge of the average activity field. Our method is very general and applies to a large class of dynamical models on dense random networks.

  1. Non-Invasive Imaging of Neuroanatomical Structures and Neural Activation with High-Resolution MRI

    PubMed Central

    Herberholz, Jens; Mishra, Subrata H.; Uma, Divya; Germann, Markus W.; Edwards, Donald H.; Potter, Kimberlee

    2011-01-01

    Several years ago, manganese-enhanced magnetic resonance imaging (MEMRI) was introduced as a new powerful tool to image active brain areas and to identify neural connections in living, non-human animals. Primarily restricted to studies in rodents and later adapted for bird species, MEMRI has recently been discovered as a useful technique for neuroimaging of invertebrate animals. Using crayfish as a model system, we highlight the advantages of MEMRI over conventional techniques for imaging of small nervous systems. MEMRI can be applied to image invertebrate nervous systems at relatively high spatial resolution, and permits identification of stimulus-evoked neural activation non-invasively. Since the selection of specific imaging parameters is critical for successful in vivo micro-imaging, we present an overview of different experimental conditions that are best suited for invertebrates. We also compare the effects of hardware and software specifications on image quality, and provide detailed descriptions of the steps necessary to prepare animals for successful imaging sessions. Careful consideration of hardware, software, experiments, and specimen preparation will promote a better understanding of this novel technique and facilitate future MEMRI studies in other laboratories. PMID:21503138

  2. Patterns of neural and behavioral activity in freely-moving Navanax inermis (Mollusca; Opisthobranchia).

    PubMed

    Leonard, J L

    1992-01-01

    As part of an ongoing neuroethological study of complex behavior in the opisthobranch mollusc, Navanax inermis, I have extended the available gross anatomical descriptions and used cuff electrodes to obtain chronic recordings from whole nerves or connectives. The major anatomical findings concern a) finer branches of the pedal nerves, particularly P3C P4 and P5; b) the distribution of nerves from the abdominal and subintestinal ganglia; and c) a possible neurohaemal area of the supraintestinal ganglion. With cuff electrodes it has been possible to get good quality recordings (often with spikes in the mv range) during the full repertoire of sexual, predatory and cannibalistic behaviors. The high degree of cryptic neural activity and the fact that in Navanax behaviors are not mutually exclusive, make it difficult to identify one-to-one correspondences between behaviors and neural patterns, However, there is an apparent correlation between the activity of a very large unit(s) on P5 and an exploratory behavior, the Face-Down head posture when it is directed at the substrate rather than prey, or a conspecific. PMID:1299122

  3. BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall

    PubMed Central

    Golkar, Armita; Lindström, Kara M.; Haaker, Jan; Öhman, Arne; Schalling, Martin; Ingvar, Martin

    2015-01-01

    Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional BDNFval66met polymorphism, underwent a fear conditioning and 24h-delayed extinction protocol while skin conductance and blood oxygenation level dependent (BOLD) responses (functional magnetic resonance imaging) were acquired. We present the first report of neural activation pattern during fear acquisition ‘and’ extinction for the BDNFval66met polymorphism using a differential conditioned stimulus (CS)+ > CS− comparison. During conditioning, we observed heightened allele dose-dependent responses in the amygdala and reduced responses in the subgenual anterior cingulate cortex in BDNFval66met met-carriers. During early extinction, 24h later, we again observed heightened responses in several regions ascribed to the fear network in met-carriers as opposed to val-carriers (insula, amygdala, hippocampus), which likely reflects fear memory recall. No differences were observed during late extinction, which likely reflects learned extinction. Our data thus support previous associations of the BDNFval66met polymorphism with neural activation in the fear and extinction network, but speak against a specific association with fear extinction processes. PMID:25103087

  4. Analgesic Neural Circuits Are Activated by Electroacupuncture at Two Sets of Acupoints

    PubMed Central

    Hu, Man-Li; Qiu, Zheng-Ying

    2016-01-01

    To investigate analgesic neural circuits activated by electroacupuncture (EA) at different sets of acupoints in the brain, goats were stimulated by EA at set of Baihui-Santai acupoints or set of Housanli acupoints for 30 min. The pain threshold was measured using the potassium iontophoresis method. The levels of c-Fos were determined with Streptavidin-Biotin Complex immunohistochemistry. The results showed pain threshold induced by EA at set of Baihui-Santai acupoints was 44.74% ± 4.56% higher than that by EA at set of Housanli acupoints (32.64% ± 5.04%). Compared with blank control, EA at two sets of acupoints increased c-Fos expression in the medial septal nucleus (MSN), the arcuate nucleus (ARC), the nucleus amygdala basalis (AB), the lateral habenula nucleus (HL), the ventrolateral periaqueductal grey (vlPAG), the locus coeruleus (LC), the nucleus raphe magnus (NRM), the pituitary gland, and spinal cord dorsal horn (SDH). Compared with EA at set of Housanli points, EA at set of Baihui-Santai points induced increased c-Fos expression in AB but decrease in MSN, the paraventricular nucleus of the hypothalamus, HL, and SDH. It suggests that ARC-PAG-NRM/LC-SDH and the hypothalamus-pituitary may be the common activated neural pathways taking part in EA-induced analgesia at the two sets of acupoints. PMID:27429635

  5. Trait self-esteem and neural activities related to self-evaluation and social feedback

    PubMed Central

    Yang, Juan; Xu, Xiaofan; Chen, Yu; Shi, Zhenhao; Han, Shihui

    2016-01-01

    Self-esteem has been associated with neural responses to self-reflection and attitude toward social feedback but in different brain regions. The distinct associations might arise from different tasks or task-related attitudes in the previous studies. The current study aimed to clarify these by investigating the association between self-esteem and neural responses to evaluation of one’s own personality traits and of others’ opinion about one’s own personality traits. We scanned 25 college students using functional MRI during evaluation of oneself or evaluation of social feedback. Trait self-esteem was measured using the Rosenberg self-esteem scale after scanning. Whole-brain regression analyses revealed that trait self-esteem was associated with the bilateral orbitofrontal activity during evaluation of one’s own positive traits but with activities in the medial prefrontal cortex, posterior cingulate, and occipital cortices during evaluation of positive social feedback. Our findings suggest that trait self-esteem modulates the degree of both affective processes in the orbitofrontal cortex during self-reflection and cognitive processes in the medial prefrontal cortex during evaluation of social feedback. PMID:26842975

  6. Trait self-esteem and neural activities related to self-evaluation and social feedback.

    PubMed

    Yang, Juan; Xu, Xiaofan; Chen, Yu; Shi, Zhenhao; Han, Shihui

    2016-01-01

    Self-esteem has been associated with neural responses to self-reflection and attitude toward social feedback but in different brain regions. The distinct associations might arise from different tasks or task-related attitudes in the previous studies. The current study aimed to clarify these by investigating the association between self-esteem and neural responses to evaluation of one's own personality traits and of others' opinion about one's own personality traits. We scanned 25 college students using functional MRI during evaluation of oneself or evaluation of social feedback. Trait self-esteem was measured using the Rosenberg self-esteem scale after scanning. Whole-brain regression analyses revealed that trait self-esteem was associated with the bilateral orbitofrontal activity during evaluation of one's own positive traits but with activities in the medial prefrontal cortex, posterior cingulate, and occipital cortices during evaluation of positive social feedback. Our findings suggest that trait self-esteem modulates the degree of both affective processes in the orbitofrontal cortex during self-reflection and cognitive processes in the medial prefrontal cortex during evaluation of social feedback. PMID:26842975

  7. Neural activation during imitation with or without performance feedback: An fMRI study.

    PubMed

    Zhang, Kaihua; Wang, Hui; Dong, Guangheng; Wang, Mengxing; Zhang, Jilei; Zhang, Hui; Meng, Weixia; Du, Xiaoxia

    2016-08-26

    In our daily lives, we often receive performance feedback (PF) during imitative learning, and we adjust our behaviors accordingly to improve performance. However, little is known regarding the neural mechanisms underlying this learning process. We hypothesized that appropriate PF would enhance neural activation or recruit additional brain areas during subsequent action imitation. Pictures of 20 different finger gestures without any social meaning were shown to participants from the first-person perspective. Imitation with or without PF was investigated by functional magnetic resonance imaging in 30 healthy subjects. The PF was given by a real person or by a computer. PF from a real person induced hyperactivation of the parietal lobe (precuneus and cuneus), cingulate cortex (posterior and anterior), temporal lobe (superior and transverse temporal gyri), and cerebellum (posterior and anterior lobes) during subsequent imitation. The positive PF and negative PF from a real person, induced the activation of more brain areas during the following imitation. The hyperactivation of the cerebellum, posterior cingulate cortex, precuneus, and cuneus suggests that the subjects exhibited enhanced motor control and visual attention during imitation after PF. Additionally, random PF from a computer had a small effect on the next imitation. We suggest that positive and accurate PF may be helpful for imitation learning. PMID:27422729

  8. Deep brain optical measurements of cell type–specific neural activity in behaving mice

    PubMed Central

    Cui, Guohong; Jun, Sang Beom; Jin, Xin; Luo, Guoxiang; Pham, Michael D; Lovinger, David M; Vogel, Steven S; Costa, Rui M

    2014-01-01

    Recent advances in genetically encoded fluorescent sensors enable the monitoring of cellular events from genetically defined groups of neurons in vivo. In this protocol, we describe how to use a time-correlated single-photon counting (tcspc)–based fiber optics system to measure the intensity, emission spectra and lifetime of fluorescent biosensors expressed in deep brain structures in freely moving mice. When combined with cre-dependent selective expression of genetically encoded ca2+ indicators (GecIs), this system can be used to measure the average neural activity from a specific population of cells in mice performing complex behavioral tasks. as an example, we used viral expression of GcaMps in striatal projection neurons (spns) and recorded the fluorescence changes associated with calcium spikes from mice performing a lever-pressing operant task. the whole procedure, consisting of virus injection, behavior training and optical recording, takes 3–4 weeks to complete. With minor adaptations, this protocol can also be applied to recording cellular events from other cell types in deep brain regions, such as dopaminergic neurons in the ventral tegmental area. the simultaneously recorded fluorescence signals and behavior events can be used to explore the relationship between the neural activity of specific brain circuits and behavior. PMID:24784819

  9. Altered Brain Activities Associated with Neural Repetition Effects in Mild Cognitive Impairment Patients.

    PubMed

    Yu, Jing; Li, Rui; Jiang, Yang; Broster, Lucas S; Li, Juan

    2016-05-11

    Older adults with mild cognitive impairment (MCI) manifest impaired explicit memory. However, studies on implicit memory such as repetition effects in persons with MCI have been limited. In the present study, 17 MCI patients and 16 healthy normal controls (NC) completed a modified delayed-match-to-sample task while undergoing functional magnetic resonance imaging. We aim to examine the neural basis of repetition; specifically, to elucidate whether and how repetition-related brain responses are altered in participants with MCI. When repeatedly rejecting distracters, both NC and MCI showed similar behavioral repetition effects; however, in both whole-brain and region-of-interest analyses of functional data, persons with MCI showed reduced repetition-driven suppression in the middle occipital and middle frontal gyrus. Further, individual difference analysis found that activation in the left middle occipital gyrus was positively correlated with rejecting reaction time and negatively correlated with accuracy rate, suggesting a predictor of repetition behavioral performance. These findings provide new evidence to support the view that neural mechanisms of repetition effect are altered in MCI who manifests compensatory repetition-related brain activities along with their neuropathology. PMID:27176074

  10. Molecular Fingerprint-based Artificial Neural Networks QSAR for Ligand Biological Activity Predictions

    PubMed Central

    Myint, Kyaw-Zeyar; Wang, Lirong; Tong, Qin; Xie, Xiang-Qun

    2012-01-01

    In this manuscript, we have reported a novel 2D fingerprint-based artificial neural network QSAR (FANN-QSAR) method in order to effectively predict biological activities of structurally diverse chemical ligands. Three different types of fingerprints, namely ECFP6, FP2 and MACCS, were used in FANN-QSAR algorithm development, and FANN-QSAR models were compared to known 3D and 2D QSAR methods using five data sets previously reported. In addition, the derived models were used to predict GPCR cannabinoid ligand binding affinities using our manually curated cannabinoid ligand database containing 1699 structurally diverse compounds with reported cannabinoid receptor subtype CB2 activities. To demonstrate its useful applications, the established FANN-QSAR algorithm was used as a virtual screening tool to search a large NCI compound database for lead cannabinoid compounds and we have discovered several compounds with good CB2 binding affinities ranging from 6.70 nM to 3.75 μM. To the best of our knowledge, this is the first report for a fingerprint-based neural network approach validated with a successful virtual screening application in identifying lead compounds. The studies proved that the FANN-QSAR method is a useful approach to predict bioactivities or properties of ligands and to find novel lead compounds for drug discovery research. PMID:22937990

  11. Human facial neural activities and gesture recognition for machine-interfacing applications

    PubMed Central

    Hamedi, M; Salleh, Sh-Hussain; Tan, TS; Ismail, K; Ali, J; Dee-Uam, C; Pavaganun, C; Yupapin, PP

    2011-01-01

    The authors present a new method of recognizing different human facial gestures through their neural activities and muscle movements, which can be used in machine-interfacing applications. Human–machine interface (HMI) technology utilizes human neural activities as input controllers for the machine. Recently, much work has been done on the specific application of facial electromyography (EMG)-based HMI, which have used limited and fixed numbers of facial gestures. In this work, a multipurpose interface is suggested that can support 2–11 control commands that can be applied to various HMI systems. The significance of this work is finding the most accurate facial gestures for any application with a maximum of eleven control commands. Eleven facial gesture EMGs are recorded from ten volunteers. Detected EMGs are passed through a band-pass filter and root mean square features are extracted. Various combinations of gestures with a different number of gestures in each group are made from the existing facial gestures. Finally, all combinations are trained and classified by a Fuzzy c-means classifier. In conclusion, combinations with the highest recognition accuracy in each group are chosen. An average accuracy >90% of chosen combinations proved their ability to be used as command controllers. PMID:22267930

  12. Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury.

    PubMed

    Dadwal, Parvati; Mahmud, Neemat; Sinai, Laleh; Azimi, Ashkan; Fatt, Michael; Wondisford, Fredric E; Miller, Freda D; Morshead, Cindi M

    2015-08-11

    The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models. PMID:26235894

  13. Activating Endogenous Neural Precursor Cells Using Metformin Leads to Neural Repair and Functional Recovery in a Model of Childhood Brain Injury

    PubMed Central

    Dadwal, Parvati; Mahmud, Neemat; Sinai, Laleh; Azimi, Ashkan; Fatt, Michael; Wondisford, Fredric E.; Miller, Freda D.; Morshead, Cindi M.

    2015-01-01

    Summary The development of cell replacement strategies to repair the injured brain has gained considerable attention, with a particular interest in mobilizing endogenous neural stem and progenitor cells (known as neural precursor cells [NPCs]) to promote brain repair. Recent work demonstrated metformin, a drug used to manage type II diabetes, promotes neurogenesis. We sought to determine its role in neural repair following brain injury. We find that metformin administration activates endogenous NPCs, expanding the size of the NPC pool and promoting NPC migration and differentiation in the injured neonatal brain in a hypoxia-ischemia (H/I) injury model. Importantly, metformin treatment following H/I restores sensory-motor function. Lineage tracking reveals that metformin treatment following H/I causes an increase in the absolute number of subependyma-derived NPCs relative to untreated H/I controls in areas associated with sensory-motor function. Hence, activation of endogenous NPCs is a promising target for therapeutic intervention in childhood brain injury models. PMID:26235894

  14. Age of acquisition modulates neural activity for both regular and irregular syntactic functions

    PubMed Central

    Hernandez, Arturo E.; Hofmann, Juliane; Kotz, Sonja A.

    2007-01-01

    Studies have found that neural activity is greater for irregular grammatical items than regular items. Findings with monolingual Spanish speakers have revealed a similar effect when making gender decisions for visually presented nouns. The current study extended previous studies by looking at the role of regularity in modulating differences in groups that differ in the age of acquisition of a language. Early and late learners of Spanish matched on measures of language proficiency were asked to make gender decisions to regular (-o for masculine and –a for feminine) and irregular items (which can end in e,l,n,r,s,t and z). Results revealed increased activity in left BA 44 for irregular compared to regular items in separate comparisons for both early and late learners. In addition, within group-comparisons revealed that neural activity for irregulars extended into left BA 47 for late learners and into left BA 6 for early learners. Direct comparisons between-groups revealed increased activity in left BA 44/45 for irregular items indicating the need for more extensive syntactic processing in late learners. The results revealed that processing of irregular grammatical gender leads to increased activity in left BA 44 and adjacent areas in the left IFG regardless of when a language is learned. Furthermore, these findings suggest differential recruitment of brain areas associated with grammatical processing in late learners. The results are discussed with regard to a model which considers L2 learning as emerging from the competitive interplay between two languages. PMID:17490895

  15. Rapid, parallel path planning by propagating wavefronts of spiking neural activity

    PubMed Central

    Ponulak, Filip; Hopfield, John J.

    2013-01-01

    Efficient path planning and navigation is critical for animals, robotics, logistics and transportation. We study a model in which spatial navigation problems can rapidly be solved in the brain by parallel mental exploration of alternative routes using propagating waves of neural activity. A wave of spiking activity propagates through a hippocampus-like network, altering the synaptic connectivity. The resulting vector field of synaptic change then guides a simulated animal to the appropriate selected target locations. We demonstrate that the navigation problem can be solved using realistic, local synaptic plasticity rules during a single passage of a wavefront. Our model can find optimal solutions for competing possible targets or learn and navigate in multiple environments. The model provides a hypothesis on the possible computational mechanisms for optimal path planning in the brain, at the same time it is useful for neuromorphic implementations, where the parallelism of information processing proposed here can fully be harnessed in hardware. PMID:23882213

  16. Ligand Biological Activity Predictions Using Fingerprint-Based Artificial Neural Networks (FANN-QSAR)

    PubMed Central

    Myint, Kyaw Z.; Xie, Xiang-Qun

    2015-01-01

    This chapter focuses on the fingerprint-based artificial neural networks QSAR (FANN-QSAR) approach to predict biological activities of structurally diverse compounds. Three types of fingerprints, namely ECFP6, FP2, and MACCS, were used as inputs to train the FANN-QSAR models. The results were benchmarked against known 2D and 3D QSAR methods, and the derived models were used to predict cannabinoid (CB) ligand binding activities as a case study. In addition, the FANN-QSAR model was used as a virtual screening tool to search a large NCI compound database for lead cannabinoid compounds. We discovered several compounds with good CB2 binding affinities ranging from 6.70 nM to 3.75 μM. The studies proved that the FANN-QSAR method is a useful approach to predict bioactivities or properties of ligands and to find novel lead compounds for drug discovery research. PMID:25502380

  17. Error-related electromyographic activity over the corrugator supercilii is associated with neural performance monitoring.

    PubMed

    Elkins-Brown, Nathaniel; Saunders, Blair; Inzlicht, Michael

    2016-02-01

    Emerging research in social and affective neuroscience has implicated a role for affect and motivation in performance monitoring and cognitive control. No study, however, has investigated whether facial electromyography (EMG) over the corrugator supercilii-a measure associated with negative affect and the exertion of effort-is related to neural performance monitoring. Here, we explored these potential relationships by simultaneously measuring the error-related negativity, error positivity (Pe), and facial EMG over the corrugator supercilii muscle during a punished, inhibitory control task. We found evidence for increased facial EMG activity over the corrugator immediately following error responses, and this activity was related to the Pe for both between- and within-subject analyses. These results are consistent with the idea that early, avoidance-motivated processes are associated with performance monitoring, and that such processes may also be related to orienting toward errors, the emergence of error awareness, or both. PMID:26470645

  18. Anti-glycated activity prediction of polysaccharides from two guava fruits using artificial neural networks.

    PubMed

    Yan, Chunyan; Lee, Jinsheng; Kong, Fansheng; Zhang, Dezhi

    2013-10-15

    High-efficiency ultrasonic treatment was used to extract the polysaccharides of Psidium guajava (PPG) and Psidium littorale (PPL). The aims of this study were to compare polysaccharide activities from these two guavas, as well as to investigate the relationship between ultrasonic conditions and anti-glycated activity. A mathematical model of anti-glycated activity was constructed with the artificial neural network (ANN) toolbox of MATLAB software. Response surface plots showed the correlation between ultrasonic conditions and bioactivity. The optimal ultrasonic conditions of PPL for the highest anti-glycated activity were predicted to be 256 W, 60 °C, and 12 min, and the predicted activity was 42.2%. The predicted highest anti-glycated activity of PPG was 27.2% under its optimal predicted ultrasonic condition. The experimental result showed that PPG and PPL possessed anti-glycated and antioxidant activities, and those of PPL were greater. The experimental data also indicated that ANN had good prediction and optimization capability. PMID:23987324

  19. Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control.

    PubMed

    Forbes, Chad E; Cox, Christine L; Schmader, Toni; Ryan, Lee

    2012-10-01

    Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces. PMID:21954239

  20. Negative stereotype activation alters interaction between neural correlates of arousal, inhibition and cognitive control

    PubMed Central

    Cox, Christine L.; Schmader, Toni; Ryan, Lee

    2012-01-01

    Priming negative stereotypes of African Americans can bias perceptions toward novel Black targets, but less is known about how these perceptions ultimately arise. Examining how neural regions involved in arousal, inhibition and control covary when negative stereotypes are activated can provide insight into whether individuals attempt to downregulate biases. Using fMRI, White egalitarian-motivated participants were shown Black and White faces at fast (32 ms) or slow (525 ms) presentation speeds. To create a racially negative stereotypic context, participants listened to violent and misogynistic rap (VMR) in the background. No music (NM) and death metal (DM) were used as control conditions in separate blocks. Fast exposure of Black faces elicited amygdala activation in the NM and VMR conditions (but not DM), that also negatively covaried with activation in prefrontal regions. Only in VMR, however, did amygdala activation for Black faces persist during slow exposure and positively covary with activation in dorsolateral prefrontal cortex while negatively covarying with activation in orbitofrontal cortex. Findings suggest that contexts that prime negative racial stereotypes seem to hinder the downregulation of amygdala activation that typically occurs when egalitarian perceivers are exposed to Black faces. PMID:21954239

  1. Adolescents' risky decision-making activates neural networks related to social cognition and cognitive control processes.

    PubMed

    Rodrigo, María José; Padrón, Iván; de Vega, Manuel; Ferstl, Evelyn C

    2014-01-01

    This study examines by means of functional magnetic resonance imaging the neural mechanisms underlying adolescents' risk decision-making in social contexts. We hypothesize that the social context could engage brain regions associated with social cognition processes and developmental changes are also expected. Sixty participants (adolescents: 17-18, and young adults: 21-22 years old) read narratives describing typical situations of decision-making in the presence of peers. They were asked to make choices in risky situations (e.g., taking or refusing a drug) or ambiguous situations (e.g., eating a hamburger or a hotdog). Risky as compared to ambiguous scenarios activated bilateral temporoparietal junction (TPJ), bilateral middle temporal gyrus (MTG), right medial prefrontal cortex, and the precuneus bilaterally; i.e., brain regions related to social cognition processes, such as self-reflection and theory of mind (ToM). In addition, brain structures related to cognitive control were active [right anterior cingulate cortex (ACC), bilateral dorsolateral prefrontal cortex (DLPFC), bilateral orbitofrontal cortex], whereas no significant clusters were obtained in the reward system (ventral striatum). Choosing the dangerous option involved a further activation of control areas (ACC) and emotional and social cognition areas (temporal pole). Adolescents employed more neural resources than young adults in the right DLPFC and the right TPJ in risk situations. When choosing the dangerous option, young adults showed a further engagement in ToM related regions (bilateral MTG) and in motor control regions related to the planning of actions (pre-supplementary motor area). Finally, the right insula and the right superior temporal gyrus were more activated in women than in men, suggesting more emotional involvement and more intensive modeling of the others' perspective in the risky conditions. These findings call for more comprehensive developmental accounts of decision-making in

  2. Inappropriate Neural Activity during a Sensitive Period in Embryogenesis Results in Persistent Seizure-like Behavior

    PubMed Central

    Giachello, Carlo N.G.; Baines, Richard A.

    2015-01-01

    Summary Maturation of neural circuits requires activity-dependent processes that underpin the emergence of appropriate behavior in the adult. It has been proposed that disruption of these events, during specific critical periods when they exert maximal influence, may lead to neurodevelopmental diseases, including epilepsy [1, 2, 3]. However, complexity of neurocircuitry, coupled with the lack of information on network formation in mammals, makes it difficult to directly investigate this hypothesis. Alternative models, including the fruit fly Drosophila melanogaster, show remarkable similarities between experimental seizure-like activity and clinical phenotypes [4, 5, 6]. In particular, a group of flies, termed bang-sensitive (bs) mutants have been extensively used to investigate the pathophysiological mechanisms underlying seizure [7, 8, 9, 10, 11, 12]. Seizure phenotype can be measured in larval stages using an electroshock assay, and this behavior in bs mutants is dramatically reduced following ingestion of typical anti-epileptic drugs (AEDs; [13]). In this study we describe a critical period of embryonic development in Drosophila during which manipulation of neural activity is sufficient to significantly influence seizure behavior at postembryonic stages. We show that inhibition of elevated activity, characteristic of bs seizure models, during the critical period is sufficient to suppress seizure. By contrast, increasing neuronal excitation during the same period in wild-type (WT) is sufficient to permanently induce a seizure behavior. Further, we show that induction of seizure in WT correlates with functional alteration of motoneuron inputs that is a characteristic of bs mutants. Induction of seizure is rescued by prior administration of AEDs, opening a new perspective for early drug intervention in the treatment of genetic epilepsy. PMID:26549258

  3. Phospholipase B activity and organophosphorus compound toxicity in cultured neural cells

    SciTech Connect

    Read, David J.; Langford, Lynda; Barbour, Helen R.; Forshaw, Philip J.; Glynn, Paul . E-mail: pg8@le.ac.uk

    2007-03-15

    Organophosphorus compounds (OP) such as phenyl saligenin phosphate (PSP) and mipafox (MPX) which cause delayed neuropathy, inhibit neuropathy target esterase (NTE), while OPs such as paraoxon (PXN) react more readily with acetylcholinesterase. In yeast and mammalian cell lines, NTE has been shown to have phospholipase B (PLB) activity which deacylates intracellular phosphatidylcholine to glycerophosphocholine (GroPCho) and can be detected by metabolic labeling with [{sup 14}C]choline. Here we investigated PLB activity in primary cultures of mouse neural cells. In cortical and cerebellar granule neurons and astrocytes, [{sup 14}C]GroPCho labeling was inhibited by PSP and MPX: phenyl dipentylphosphinate (PDPP), a non-neuropathic NTE inhibitor, was more potent, while PXN, was substantially less so. In all three cell types, conversion of [{sup 14}C]phosphatidylcholine to [{sup 14}C]GroPCho over 24 h was relatively small (2.3-14%). Consequently, even with > 80% inhibition of [{sup 14}C]GroPCho production, increased [{sup 14}C]phosphatidylcholine was not detected. At concentrations of 1-10 {mu}M, only PSP was cytotoxic to cortical and cerebellar granule neurons after 24-h exposure. Moreover, dramatic changes in glial cell morphology were induced by PSP, but not PDPP or MPX, with rapid (2-3 h) rounding up of astrocytes and of Schwann cells in cultures of dissociated mouse dorsal root ganglia. We conclude that PLB activity is present in a variety of cultured mouse neural cell types but that acute loss of this activity is not cytotoxic. Conversely, the rapid toxic effects of PSP in vitro suggest that a serine hydrolase distinct from NTE is required continuously by neurons and glia.

  4. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

    PubMed Central

    Doll, Caleb A.; Broadie, Kendal

    2014-01-01

    Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent (A-D) developmental processes are specifically impaired in autism spectrum disorders (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our insights into normal A-D neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic fragile X syndrome (FXS), a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in A-D critical period processes. The fragile X mental retardation protein (FMRP) is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the A-D remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor A-D processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of A-D mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model. PMID:24570656

  5. Adolescents’ risky decision-making activates neural networks related to social cognition and cognitive control processes

    PubMed Central

    Rodrigo, María José; Padrón, Iván; de Vega, Manuel; Ferstl, Evelyn C.

    2014-01-01

    This study examines by means of functional magnetic resonance imaging the neural mechanisms underlying adolescents’ risk decision-making in social contexts. We hypothesize that the social context could engage brain regions associated with social cognition processes and developmental changes are also expected. Sixty participants (adolescents: 17–18, and young adults: 21–22 years old) read narratives describing typical situations of decision-making in the presence of peers. They were asked to make choices in risky situations (e.g., taking or refusing a drug) or ambiguous situations (e.g., eating a hamburger or a hotdog). Risky as compared to ambiguous scenarios activated bilateral temporoparietal junction (TPJ), bilateral middle temporal gyrus (MTG), right medial prefrontal cortex, and the precuneus bilaterally; i.e., brain regions related to social cognition processes, such as self-reflection and theory of mind (ToM). In addition, brain structures related to cognitive control were active [right anterior cingulate cortex (ACC), bilateral dorsolateral prefrontal cortex (DLPFC), bilateral orbitofrontal cortex], whereas no significant clusters were obtained in the reward system (ventral striatum). Choosing the dangerous option involved a further activation of control areas (ACC) and emotional and social cognition areas (temporal pole). Adolescents employed more neural resources than young adults in the right DLPFC and the right TPJ in risk situations. When choosing the dangerous option, young adults showed a further engagement in ToM related regions (bilateral MTG) and in motor control regions related to the planning of actions (pre-supplementary motor area). Finally, the right insula and the right superior temporal gyrus were more activated in women than in men, suggesting more emotional involvement and more intensive modeling of the others’ perspective in the risky conditions. These findings call for more comprehensive developmental accounts of decision

  6. Telencephalic neural activation following passive avoidance learning in a terrestrial toad.

    PubMed

    Puddington, Martín M; Daneri, M Florencia; Papini, Mauricio R; Muzio, Rubén N

    2016-12-15

    The present study explores passive avoidance learning and its neural basis in toads (Rhinella arenarum). In Experiment 1, two groups of toads learned to move from a lighted compartment into a dark compartment. After responding, animals in the experimental condition were exposed to an 800-mM strongly hypertonic NaCl solution that leads to weight loss. Control animals received exposure to a 300-mM slightly hypertonic NaCl solution that leads to neither weight gain nor loss. After 10 daily acquisition trials, animals in the experimental group showed significantly longer latency to enter the dark compartment. Additionally, 10 daily trials in which both groups received the 300-mM NaCl solution after responding eliminated this group effect. Thus, experimental animals showed gradual acquisition and extinction of a passive avoidance respond. Experiment 2 replicated the gradual acquisition effect, but, after the last trial, animals were sacrificed and neural activation was assessed in five brain regions using AgNOR staining for nucleoli-an index of brain activity. Higher activation in the experimental animals, relative to controls, was observed in the amygdala and striatum. Group differences in two other regions, lateral pallium and septum, were borderline, but nonsignificant, whereas group differences in the medial pallium were nonsignificant. These preliminary results suggest that a striatal-amygdala activation could be a key component of the brain circuit controlling passive avoidance learning in amphibians. The results are discussed in relation to the results of analogous experiments with other vertebrates. PMID:27498147

  7. Visual avoidance in phobia: particularities in neural activity, autonomic responding, and cognitive risk evaluations

    PubMed Central

    Aue, Tatjana; Hoeppli, Marie-Eve; Piguet, Camille; Sterpenich, Virginie; Vuilleumier, Patrik

    2013-01-01

    We investigated the neural mechanisms and the autonomic and cognitive responses associated with visual avoidance behavior in spider phobia. Spider phobic and control participants imagined visiting different forest locations with the possibility of encountering spiders, snakes, or birds (neutral reference category). In each experimental trial, participants saw a picture of a forest location followed by a picture of a spider, snake, or bird, and then rated their personal risk of encountering these animals in this context, as well as their fear. The greater the visual avoidance of spiders that a phobic participant demonstrated (as measured by eye tracking), the higher were her autonomic arousal and neural activity in the amygdala, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and precuneus at picture onset. Visual avoidance of spiders in phobics also went hand in hand with subsequently reduced cognitive risk of encounters. Control participants, in contrast, displayed a positive relationship between gaze duration toward spiders, on the one hand, and autonomic responding, as well as OFC, ACC, and precuneus activity, on the other hand. In addition, they showed reduced encounter risk estimates when they looked longer at the animal pictures. Our data are consistent with the idea that one reason for phobics to avoid phobic information may be grounded in heightened activity in the fear circuit, which signals potential threat. Because of the absence of alternative efficient regulation strategies, visual avoidance may then function to down-regulate cognitive risk evaluations for threatening information about the phobic stimuli. Control participants, in contrast, may be characterized by a different coping style, whereby paying visual attention to potentially threatening information may help them to actively down-regulate cognitive evaluations of risk. PMID:23754994

  8. Automated Visual Cognitive Tasks for Recording Neural Activity Using a Floor Projection Maze

    PubMed Central

    Kent, Brendon W.; Yang, Fang-Chi; Burwell, Rebecca D.

    2014-01-01

    Neuropsychological tasks used in primates to investigate mechanisms of learning and memory are typically visually guided cognitive tasks. We have developed visual cognitive tasks for rats using the Floor Projection Maze1,2 that are optimized for visual abilities of rats permitting stronger comparisons of experimental findings with other species. In order to investigate neural correlates of learning and memory, we have integrated electrophysiological recordings into fully automated cognitive tasks on the Floor Projection Maze1,2. Behavioral software interfaced with an animal tracking system allows monitoring of the animal's behavior with precise control of image presentation and reward contingencies for better trained animals. Integration with an in vivo electrophysiological recording system enables examination of behavioral correlates of neural activity at selected epochs of a given cognitive task. We describe protocols for a model system that combines automated visual presentation of information to rodents and intracranial reward with electrophysiological approaches. Our model system offers a sophisticated set of tools as a framework for other cognitive tasks to better isolate and identify specific mechanisms contributing to particular cognitive processes. PMID:24638057

  9. Injury in aged animals robustly activates quiescent olfactory neural stem cells

    PubMed Central

    Brann, Jessica H.; Ellis, Deandrea P.; Ku, Benson S.; Spinazzi, Eleonora F.; Firestein, Stuart

    2015-01-01

    While the capacity of the olfactory epithelium (OE) to generate sensory neurons continues into middle age in mice, it is presumed that this regenerative potential is present throughout all developmental stages. However, little experimental evidence exists to support the idea that this regenerative capacity remains in late adulthood, and questions about the functionality of neurons born at these late stages remain unanswered. Here, we extend our previous work in the VNO to investigate basal rates of proliferation in the OE, as well as after olfactory bulbectomy (OBX), a commonly used surgical lesion. In addition, we show that the neural stem cell retains its capacity to generate mature olfactory sensory neurons in aged animals. Finally, we demonstrate that regardless of age, a stem cell in the OE, the horizontal basal cell (HBC), exhibits a morphological switch from a flattened, quiescent phenotype to a pyramidal, proliferative phenotype following chemical lesion in aged animals. These findings provide new insights into determining whether an HBC is active or quiescent based on a structural feature as opposed to a biochemical one. More importantly, it suggests that neural stem cells in aged mice are responsive to the same signals triggering proliferation as those observed in young mice. PMID:26500487

  10. Determination of DPPH free radical scavenging activity: application of artificial neural networks.

    PubMed

    Musa, Khalid Hamid; Abdullah, Aminah; Al-Haiqi, Ahmed

    2016-03-01

    A new computational approach for the determination of 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity (DPPH-RSA) in food is reported, based on the concept of machine learning. Trolox standard was mix with DPPH at different concentrations to produce different colors from purple to yellow. Artificial neural network (ANN) was trained on a typical set of images of the DPPH radical reacting with different levels of Trolox. This allowed the neural network to classify future images of any sample into the correct class of RSA level. The ANN was then able to determine the DPPH-RSA of cinnamon, clove, mung bean, red bean, red rice, brown rice, black rice and tea extract and the results were compared with data obtained using a spectrophotometer. The application of ANN correlated well to the spectrophotometric classical procedure and thus do not require the use of spectrophotometer, and it could be used to obtain semi-quantitative results of DPPH-RSA. PMID:26471610

  11. Effects of vibratory stimulation-induced kinesthetic illusions on the neural activities of patients with stroke

    PubMed Central

    Kodama, Takayuki; Nakano, Hideki; Ohsugi, Hironori; Murata, Shin

    2016-01-01

    [Purpose] This study evaluated the influence of vibratory stimulation-induced kinesthetic illusion on brain function after stroke. [Subjects] Twelve healthy individuals and 13 stroke patients without motor or sensory loss participated. [Methods] Electroencephalograms were taken at rest and during vibratory stimulation. As a neurophysiological index of brain function, we measured the μ-rhythm, which is present mainly in the kinesthetic cortex and is attenuated by movement or motor imagery and compared the data using source localization analyses in the Standardized Low Resolution Brain Electromagnetic Tomography (sLORETA) program. [Results] At rest, μ-rhythms appeared in the sensorimotor and supplementary motor cortices in both healthy controls and stroke patients. Under vibratory stimulation, no μ-rhythm appeared in the sensorimotor cortex of either group. Moreover, in the supplementary motor area, which stores the motor imagery required for kinesthetic illusions, the μ-rhythms of patients were significantly stronger than those of the controls, although the μ-rhythms of both groups were reduced. Thus, differences in neural activity in the supplementary motor area were apparent between the subject groups. [Conclusion] Kinesthetic illusions do occur in patients with motor deficits due to stroke. The neural basis of the supplementary motor area in stroke patients may be functionally different from that found in healthy controls. PMID:27065525

  12. Neural crest–derived SEMA3C activates endothelial NRP1 for cardiac outflow tract septation

    PubMed Central

    Plein, Alice; Calmont, Amélie; Fantin, Alessandro; Denti, Laura; Anderson, Naomi A.; Scambler, Peter J.; Ruhrberg, Christiana

    2015-01-01

    In mammals, the outflow tract (OFT) of the developing heart septates into the base of the pulmonary artery and aorta to guide deoxygenated right ventricular blood into the lungs and oxygenated left ventricular blood into the systemic circulation. Accordingly, defective OFT septation is a life-threatening condition that can occur in both syndromic and nonsyndromic congenital heart disease. Even though studies of genetic mouse models have previously revealed a requirement for VEGF-A, the class 3 semaphorin SEMA3C, and their shared receptor neuropilin 1 (NRP1) in OFT development, the precise mechanism by which these proteins orchestrate OFT septation is not yet understood. Here, we have analyzed a complementary set of ligand-specific and tissue-specific mouse mutants to show that neural crest–derived SEMA3C activates NRP1 in the OFT endothelium. Explant assays combined with gene-expression studies and lineage tracing further demonstrated that this signaling pathway promotes an endothelial-to-mesenchymal transition that supplies cells to the endocardial cushions and repositions cardiac neural crest cells (NCCs) within the OFT, 2 processes that are essential for septal bridge formation. These findings elucidate a mechanism by which NCCs cooperate with endothelial cells in the developing OFT to enable the postnatal separation of the pulmonary and systemic circulation. PMID:26053665

  13. Neural activity in the medial temporal lobe reveals the fidelity of mental time travel.

    PubMed

    Kragel, James E; Morton, Neal W; Polyn, Sean M

    2015-02-18

    Neural circuitry in the medial temporal lobe (MTL) is critically involved in mental time travel, which involves the vivid retrieval of the details of past experience. Neuroscientific theories propose that the MTL supports memory of the past by retrieving previously encoded episodic information, as well as by reactivating a temporal code specifying the position of a particular event within an episode. However, the neural computations supporting these abilities are underspecified. To test hypotheses regarding the computational mechanisms supported by different MTL subregions during mental time travel, we developed a computational model that linked a blood oxygenation level-dependent signal to cognitive operations, allowing us to predict human performance in a memory search task. Activity in the posterior MTL, including parahippocampal cortex, reflected how strongly one reactivates the temporal context of a retrieved memory, allowing the model to predict whether the next memory will correspond to a nearby moment in the study episode. A signal in the anterior MTL, including perirhinal cortex, indicated the successful retrieval of list items, without providing information regarding temporal organization. A hippocampal signal reflected both processes, consistent with theories that this region binds item and context information together to form episodic memories. These findings provide evidence for modern theories that describe complementary roles of the hippocampus and surrounding parahippocampal and perirhinal cortices during the retrieval of episodic memories, shaping how humans revisit the past. PMID:25698731

  14. DETECTING ACTIVE GALACTIC NUCLEI USING MULTI-FILTER IMAGING DATA. II. INCORPORATING ARTIFICIAL NEURAL NETWORKS

    SciTech Connect

    Dong, X. Y.; De Robertis, M. M.

    2013-10-01

    This is the second paper of the series Detecting Active Galactic Nuclei Using Multi-filter Imaging Data. In this paper we review shapelets, an image manipulation algorithm, which we employ to adjust the point-spread function (PSF) of galaxy images. This technique is used to ensure the image in each filter has the same and sharpest PSF, which is the preferred condition for detecting AGNs using multi-filter imaging data as we demonstrated in Paper I of this series. We apply shapelets on Canada-France-Hawaii Telescope Legacy Survey Wide Survey ugriz images. Photometric parameters such as effective radii, integrated fluxes within certain radii, and color gradients are measured on the shapelets-reconstructed images. These parameters are used by artificial neural networks (ANNs) which yield: photometric redshift with an rms of 0.026 and a regression R-value of 0.92; galaxy morphological types with an uncertainty less than 2 T types for z ≤ 0.1; and identification of galaxies as AGNs with 70% confidence, star-forming/starburst (SF/SB) galaxies with 90% confidence, and passive galaxies with 70% confidence for z ≤ 0.1. The incorporation of ANNs provides a more reliable technique for identifying AGN or SF/SB candidates, which could be very useful for large-scale multi-filter optical surveys that also include a modest set of spectroscopic data sufficient to train neural networks.

  15. Development of a computational model on the neural activity patterns of a visual working memory in a hierarchical feedforward Network

    NASA Astrophysics Data System (ADS)

    An, Soyoung; Choi, Woochul; Paik, Se-Bum

    2015-11-01

    Understanding the mechanism of information processing in the human brain remains a unique challenge because the nonlinear interactions between the neurons in the network are extremely complex and because controlling every relevant parameter during an experiment is difficult. Therefore, a simulation using simplified computational models may be an effective approach. In the present study, we developed a general model of neural networks that can simulate nonlinear activity patterns in the hierarchical structure of a neural network system. To test our model, we first examined whether our simulation could match the previously-observed nonlinear features of neural activity patterns. Next, we performed a psychophysics experiment for a simple visual working memory task to evaluate whether the model could predict the performance of human subjects. Our studies show that the model is capable of reproducing the relationship between memory load and performance and may contribute, in part, to our understanding of how the structure of neural circuits can determine the nonlinear neural activity patterns in the human brain.

  16. Neural Substrates Underlying the Passive Observation and Active Control of Translational Egomotion

    PubMed Central

    Chen, Ching-fu; Sereno, Martin I.

    2015-01-01

    Moving or static obstacles often get in the way while walking in daily life. Avoiding obstacles involves both perceptual processing of motion information and controlling appropriate defensive movements. Several higher-level motion areas, including the ventral intraparietal area (VIP), medial superior temporal area, parieto-insular vestibular cortex (PIVC), areas V6 and V6A, and cingulate sulcus visual area, have been identified in humans by passive viewing of optic flow patterns that simulate egomotion and object motion. However, the roles of these areas in the active control of egomotion in the real world remain unclear. Here, we used functional magnetic resonance imaging (fMRI) to map the neural substrates underlying the passive observation and active control of translational egomotion in humans. A wide-field virtual reality environment simulated a daily scenario where doors randomly swing outward while walking in a hallway. The stimuli of door-dodging events were essentially the same in two event-related fMRI experiments, which compared passive and active dodges in response to swinging doors. Passive dodges were controlled by a computer program, while active dodges were controlled by the subject. Passive dodges activated several higher-level areas distributed across three dorsal motion streams in the temporal, parietal, and cingulate cortex. Active dodges most strongly activated the temporal–vestibular stream, with peak activation located in the right PIVC. Other higher-level motion areas including VIP showed weaker to no activation in active dodges. These results suggest that PIVC plays an active role in sensing and guiding translational egomotion that moves an observer aside from impending obstacles. PMID:25762672

  17. Neural substrates underlying the passive observation and active control of translational egomotion.

    PubMed

    Huang, Ruey-Song; Chen, Ching-Fu; Sereno, Martin I

    2015-03-11

    Moving or static obstacles often get in the way while walking in daily life. Avoiding obstacles involves both perceptual processing of motion information and controlling appropriate defensive movements. Several higher-level motion areas, including the ventral intraparietal area (VIP), medial superior temporal area, parieto-insular vestibular cortex (PIVC), areas V6 and V6A, and cingulate sulcus visual area, have been identified in humans by passive viewing of optic flow patterns that simulate egomotion and object motion. However, the roles of these areas in the active control of egomotion in the real world remain unclear. Here, we used functional magnetic resonance imaging (fMRI) to map the neural substrates underlying the passive observation and active control of translational egomotion in humans. A wide-field virtual reality environment simulated a daily scenario where doors randomly swing outward while walking in a hallway. The stimuli of door-dodging events were essentially the same in two event-related fMRI experiments, which compared passive and active dodges in response to swinging doors. Passive dodges were controlled by a computer program, while active dodges were controlled by the subject. Passive dodges activated several higher-level areas distributed across three dorsal motion streams in the temporal, parietal, and cingulate cortex. Active dodges most strongly activated the temporal-vestibular stream, with peak activation located in the right PIVC. Other higher-level motion areas including VIP showed weaker to no activation in active dodges. These results suggest that PIVC plays an active role in sensing and guiding translational egomotion that moves an observer aside from impending obstacles. PMID:25762672

  18. Neural activation in cognitive motor processes: comparing motor imagery and observation of gymnastic movements.

    PubMed

    Munzert, Jörn; Zentgraf, Karen; Stark, Rudolf; Vaitl, Dieter

    2008-07-01

    The simulation concept suggested by Jeannerod (Neuroimage 14:S103-S109, 2001) defines the S-states of action observation and mental simulation of action as action-related mental states lacking overt execution. Within this framework, similarities and neural overlap between S-states and overt execution are interpreted as providing the common basis for the motor representations implemented within the motor system. The present brain imaging study compared activation overlap and differential activation during mental simulation (motor imagery) with that while observing gymnastic movements. The fMRI conjunction analysis revealed overlapping activation for both S-states in primary motor cortex, premotor cortex, and the supplementary motor area as well as in the intraparietal sulcus, cerebellar hemispheres, and parts of the basal ganglia. A direct contrast between the motor imagery and observation conditions revealed stronger activation for imagery in the posterior insula and the anterior cingulate gyrus. The hippocampus, the superior parietal lobe, and the cerebellar areas were differentially activated in the observation condition. In general, these data corroborate the concept of action-related S-states because of the high overlap in core motor as well as in motor-related areas. We argue that differential activity between S-states relates to task-specific and modal information processing. PMID:18425505

  19. Data on the impact of SSRIs and depression symptoms on the neural activities in obsessive-compulsive disorder at rest.

    PubMed

    Chen, Yunhui; Juhas, Michal; Greenshaw, Andrew J; Hu, Qiang; Meng, Xin; Cui, Hongsheng; Ding, Yongzhuo; Kang, Lu; Zhang, Yubo; Wang, Yuhua; Cui, Guangcheng; Li, Ping

    2016-09-01

    The data provided here related to our research article (Chen et al., 2016) [1]. We provide whole-brain intrinsic functional connectivity patterns in obsessive-compulsive disorder at resting-state [1]. This article also provides supplementary information to our research article, i.e., between - group comparisons of the effect of selective serotonin reuptake inhibitors (SSRIs) and combined depression symptoms on resting-state neural activities in obsessive-compulsive disorder. The data presented here provide novel insights into the effect of SSRIs and combined depression symptoms on the neural activities at rest. PMID:27504477

  20. Remote modulation of neural activities via near-infrared triggered release of biomolecules.

    PubMed

    Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

    2015-10-01

    The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically

  1. Altered neural activity in the `when' pathway during temporal processing in fragile X premutation carriers

    PubMed Central

    Kim, So-Yeon; Tassone, Flora; Simon, Tony J.; Rivera, Susan M.

    2016-01-01

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (>200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55–200 of CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory (SWM and TWM) tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the `when pathway' (i.e., the right temporoparietal junction: TPJ) during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression (i.e., CGG repeat size and FMR1 mRNA) suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression. PMID:24398265

  2. Seasonal prediction of tropical cyclone activity over the north Indian Ocean using three artificial neural networks

    NASA Astrophysics Data System (ADS)

    Nath, Sankar; Kotal, S. D.; Kundu, P. K.

    2016-03-01

    Three artificial neural network (ANN) methods, namely, multilayer perceptron (MLP), radial basis function (RBF) and generalized regression neural network (GRNN) are utilized to predict the seasonal tropical cyclone (TC) activity over the north Indian Ocean (NIO) during the post-monsoon season (October, November, December). The frequency of TC and large-scale climate variables derived from NCEP/NCAR reanalysis dataset of resolution 2.5° × 2.5° were analyzed for the period 1971-2013. Data for the years 1971-2002 were used for the development of the models, which were tested with independent sample data for the year 2003-2013. Using the correlation analysis, the five large-scale climate variables, namely, geopotential height at 500 hPa, relative humidity at 500 hPa, sea-level pressure, zonal wind at 700 hPa and 200 hPa for the preceding month September, are selected as potential predictors of the post-monsoon season TC activity. The result reveals that all the three different ANN methods are able to provide satisfactory forecast in terms of the various metrics, such as root mean-square error (RMSE), standard deviation (SD), correlation coefficient (r), and bias and index of agreement (d). Additionally, leave-one-out cross validation (LOOCV) method is also performed and the forecast skill is evaluated. The results show that the MLP model is found to be superior to the other two models (RBF, GRNN). The (MLP) is expected to be very useful to operational forecasters for prediction of TC activity.

  3. Altered neural activity in the 'when' pathway during temporal processing in fragile X premutation carriers.

    PubMed

    Kim, So-Yeon; Tassone, Flora; Simon, Tony J; Rivera, Susan M

    2014-03-15

    Mutations of the fragile X mental retardation 1 (FMR1) gene are the genetic cause of fragile X syndrome (FXS). Large expansions of the CGG repeat (>200 repeats) consequently result in transcriptional silencing of the FMR1 gene and deficiency/absence of the FMR1 protein (FMRP). Carriers with a premutation allele (55-200 of CGG repeats) are often associated with mildly reduced levels of FMRP and/or elevated levels of FMR1 mRNA. Recent studies have shown that infants with FXS exhibit severely reduced resolution of temporal attention, whereas spatial resolution of attention is not impaired. Following from these findings in the full mutation, the current study used fMRI to examine whether premutation carriers would exhibit atypical temporal processing at behavioral and/or neural levels. Using spatial and temporal working memory (SWM and TWM) tasks, separately tagging spatial and temporal processing, we demonstrated that neurotypical adults showed greater activation in the 'when pathway' (i.e., the right temporoparietal junction: TPJ) during TWM retrieval than SWM retrieval. However, premutation carriers failed to show this increased involvement of the right TPJ during retrieval of temporal information. Further, multiple regression analyses on right TPJ activation and FMR1 gene expression (i.e., CGG repeat size and FMR1 mRNA) suggests that elevated FMR1 mRNA level is a powerful predictor accounting for reduced right TPJ activation associated with temporal processing in premutation carriers. In conclusion, the current study provides the first evidence on altered neural correlates of temporal processing in adults with the premutation, explained by their FMR1 gene expression. PMID:24398265

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  6. Short curcumin treatment modulates oxidative stress, arginase activity, aberrant crypt foci, and TGF-β1 and HES-1 transcripts in 1,2-dimethylhydrazine-colon carcinogenesis in mice.

    PubMed

    Bounaama, Abdelkader; Djerdjouri, Bahia; Laroche-Clary, Audrey; Le Morvan, Valérie; Robert, Jacques

    2012-12-16

    This study investigated the effect of short curcumin treatment, a natural antioxidant on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in mice. The incidence of aberrant crypt foci (ACF) was 100%, with 54 ± 6 per colon, 10 weeks after the first DMH injection and reached 67 ± 12 per colon after 12 weeks. A high level of undifferentiated goblet cells and a weak apoptotic activity were shown in dysplastic ACF. The morphological alterations of colonic mucosa were associated to severe oxidative stress ratio with 43% increase in malondialdehyde vs. 36% decrease in GSH. DMH also increased inducible nitric synthase (iNOS) mRNA transcripts (250%), nitrites level (240%) and arginase activity (296%), leading to nitrosative stress and cell proliferation. Curcumin treatment, starting at week 10 post-DMH injection for 14 days, reduced the number of ACF (40%), iNOS expression (25%) and arginase activity (73%), and improved redox status by approximately 46%, compared to DMH-treated mice. Moreover, curcumin induced apoptosis of dysplastic ACF cells without restoring goblet cells differentiation. Interestingly, curcumin induced a parallel increase in TGF-β1 and HES-1 transcripts (42% and 26%, respectively). In conclusion, the protective effect of curcumin was driven by the reduction of arginase activity and nitrosative stress. The up regulation of TGF-β1 and HES-1 expression by curcumin suggests for the first time, a potential interplay between these signalling pathways in the chemoprotective mechanism of curcumin. PMID:22982865

  7. Intermittent reductions in respiratory neural activity elicit spinal TNF-α-independent, atypical PKC-dependent inactivity-induced phrenic motor facilitation

    PubMed Central

    Baertsch, Nathan A.

    2015-01-01

    In many neural networks, mechanisms of compensatory plasticity respond to prolonged reductions in neural activity by increasing cellular excitability or synaptic strength. In the respiratory control system, a prolonged reduction in synaptic inputs to the phrenic motor pool elicits a TNF-α- and atypical PKC-dependent form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although iPMF may be elicited by a prolonged reduction in respiratory neural activity, iPMF is more efficiently induced when reduced respiratory neural activity (neural apnea) occurs intermittently. Mechanisms giving rise to iPMF following intermittent neural apnea are unknown. The purpose of this study was to test the hypothesis that iPMF following intermittent reductions in respiratory neural activity requires spinal TNF-α and aPKC. Phrenic motor output was recorded in anesthetized and ventilated rats exposed to brief intermittent (5, ∼1.25 min), brief sustained (∼6.25 min), or prolonged sustained (30 min) neural apnea. iPMF was elicited following brief intermittent and prolonged sustained neural apnea, but not following brief sustained neural apnea. Unlike iPMF following prolonged neural apnea, spinal TNF-α was not required to initiate iPMF during intermittent neural apnea; however, aPKC was still required for its stabilization. These results suggest that different patterns of respiratory neural activity induce iPMF through distinct cellular mechanisms but ultimately converge on a similar downstream pathway. Understanding the diverse cellular mechanisms that give rise to inactivity-induced respiratory plasticity may lead to development of novel therapeutic strategies to treat devastating respiratory control disorders when endogenous compensatory mechanisms fail. PMID:25673781

  8. Intermittent reductions in respiratory neural activity elicit spinal TNF-α-independent, atypical PKC-dependent inactivity-induced phrenic motor facilitation.

    PubMed

    Baertsch, Nathan A; Baker-Herman, Tracy L

    2015-04-15

    In many neural networks, mechanisms of compensatory plasticity respond to prolonged reductions in neural activity by increasing cellular excitability or synaptic strength. In the respiratory control system, a prolonged reduction in synaptic inputs to the phrenic motor pool elicits a TNF-α- and atypical PKC-dependent form of spinal plasticity known as inactivity-induced phrenic motor facilitation (iPMF). Although iPMF may be elicited by a prolonged reduction in respiratory neural activity, iPMF is more efficiently induced when reduced respiratory neural activity (neural apnea) occurs intermittently. Mechanisms giving rise to iPMF following intermittent neural apnea are unknown. The purpose of this study was to test the hypothesis that iPMF following intermittent reductions in respiratory neural activity requires spinal TNF-α and aPKC. Phrenic motor output was recorded in anesthetized and ventilated rats exposed to brief intermittent (5, ∼1.25 min), brief sustained (∼6.25 min), or prolonged sustained (30 min) neural apnea. iPMF was elicited following brief intermittent and prolonged sustained neural apnea, but not following brief sustained neural apnea. Unlike iPMF following prolonged neural apnea, spinal TNF-α was not required to initiate iPMF during intermittent neural apnea; however, aPKC was still required for its stabilization. These results suggest that different patterns of respiratory neural activity induce iPMF through distinct cellular mechanisms but ultimately converge on a similar downstream pathway. Understanding the diverse cellular mechanisms that give rise to inactivity-induced respiratory plasticity may lead to development of novel therapeutic strategies to treat devastating respiratory control disorders when endogenous compensatory mechanisms fail. PMID:25673781

  9. Dissociation between Neural Signatures of Stimulus and Choice in Population Activity of Human V1 during Perceptual Decision-Making

    PubMed Central

    Choe, Kyoung Whan; Blake, Randolph

    2014-01-01

    Primary visual cortex (V1) forms the initial cortical representation of objects and events in our visual environment, and it distributes information about that representation to higher cortical areas within the visual hierarchy. Decades of work have established tight linkages between neural activity occurring in V1 and features comprising the retinal image, but it remains debatable how that activity relates to perceptual decisions. An actively debated question is the extent to which V1 responses determine, on a trial-by-trial basis, perceptual choices made by observers. By inspecting the population activity of V1 from human observers engaged in a difficult visual discrimination task, we tested one essential prediction of the deterministic view: choice-related activity, if it exists in V1, and stimulus-related activity should occur in the same neural ensemble of neurons at the same time. Our findings do not support this prediction: while cortical activity signifying the variability in choice behavior was indeed found in V1, that activity was dissociated from activity representing stimulus differences relevant to the task, being advanced in time and carried by a different neural ensemble. The spatiotemporal dynamics of population responses suggest that short-term priors, perhaps formed in higher cortical areas involved in perceptual inference, act to modulate V1 activity prior to stimulus onset without modifying subsequent activity that actually represents stimulus features within V1. PMID:24523561

  10. Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory.

    PubMed

    Doll, Caleb A; Broadie, Kendal

    2015-04-01

    The activity-dependent refinement of neural circuit connectivity during critical periods of brain development is essential for optimized behavioral performance. We hypothesize that this mechanism is defective in fragile X syndrome (FXS), the leading heritable cause of intellectual disability and autism spectrum disorders. Here, we use optogenetic tools in the Drosophila FXS disease model to test activity-dependent dendritogenesis in two extrinsic neurons of the mushroom body (MB) learning and memory brain center: (1) the input projection neuron (PN) innervating Kenyon cells (KCs) in the MB calyx microglomeruli and (2) the output MVP2 neuron innervated by KCs in the MB peduncle. Both input and output neuron classes exhibit distinctive activity-dependent critical period dendritic remodeling. MVP2 arbors expand in Drosophila mutants null for fragile X mental retardation 1 (dfmr1), as well as following channelrhodopsin-driven depolarization during critical period development, but are reduced by halorhodopsin-driven hyperpolarization. Optogenetic manipulation of PNs causes the opposite outcome--reduced dendritic arbors following channelrhodopsin depolarization and expanded arbors following halorhodopsin hyperpolarization during development. Importantly, activity-dependent dendritogenesis in both neuron classes absolutely requires dfmr1 during one developmental window. These results show that dfmr1 acts in a neuron type-specific activity-dependent manner for sculpting dendritic arbors during early-use, critical period development of learning and memory circuitry in the Drosophila brain. PMID:25804740

  11. Chronic social stress in puberty alters appetitive male sexual behavior and neural metabolic activity.

    PubMed

    Bastida, Christel C; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J; Wommack, Joel C; Delville, Yvon

    2014-07-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation were altered by social subjugation. PMID:24852486

  12. Chronic Social Stress in Puberty Alters Appetitive Male Sexual Behavior and Neural Metabolic Activity

    PubMed Central

    Bastida, Christel C.; Puga, Frank; Gonzalez-Lima, Francisco; Jennings, Kimberly J.; Wommack, Joel C.; Delville, Yvon

    2014-01-01

    Repeated social subjugation in early puberty lowers testosterone levels. We used hamsters to investigate the effects of social subjugation on male sexual behavior and metabolic activity within neural systems controlling social and motivational behaviors. Subjugated animals were exposed daily to aggressive adult males in early puberty for postnatal days 28 to 42, while control animals were placed in empty clean cages. On postnatal day 45, they were tested for male sexual behavior in the presence of receptive female. Alternatively, they were tested for mate choice after placement at the base of a Y-maze containing a sexually receptive female in one tip of the maze and an ovariectomized one on the other. Social subjugation did not affect the capacity to mate with receptive females. Although control animals were fast to approach females and preferred ovariectomized individuals, subjugated animals stayed away from them and showed no preference. Cytochrome oxidase activity was reduced within the preoptic area and ventral tegmental area in subjugated hamsters. In addition, the correlation of metabolic activity of these areas with the bed nucleus of the stria terminalis and anterior parietal cortex changed significantly from positive in controls to negative in subjugated animals. These data show that at mid-puberty, while male hamsters are capable of mating, their appetitive sexual behavior is not fully mature and this aspect of male sexual behavior is responsive to social subjugation. Furthermore, metabolic activity and coordination of activity in brain areas related to sexual behavior and motivation was altered by social subjugation. PMID:24852486

  13. Bayesian Inference for Neural Electromagnetic Source Localization: Analysis of MEG Visual Evoked Activity

    SciTech Connect

    George, J.S.; Schmidt, D.M.; Wood, C.C.

    1999-02-01

    We have developed a Bayesian approach to the analysis of neural electromagnetic (MEG/EEG) data that can incorporate or fuse information from other imaging modalities and addresses the ill-posed inverse problem by sarnpliig the many different solutions which could have produced the given data. From these samples one can draw probabilistic inferences about regions of activation. Our source model assumes a variable number of variable size cortical regions of stimulus-correlated activity. An active region consists of locations on the cortical surf ace, within a sphere centered on some location in cortex. The number and radi of active regions can vary to defined maximum values. The goal of the analysis is to determine the posterior probability distribution for the set of parameters that govern the number, location, and extent of active regions. Markov Chain Monte Carlo is used to generate a large sample of sets of parameters distributed according to the posterior distribution. This sample is representative of the many different source distributions that could account for given data, and allows identification of probable (i.e. consistent) features across solutions. Examples of the use of this analysis technique with both simulated and empirical MEG data are presented.

  14. Activity-dependent FMRP requirements in development of the neural circuitry of learning and memory

    PubMed Central

    Doll, Caleb A.; Broadie, Kendal

    2015-01-01

    The activity-dependent refinement of neural circuit connectivity during critical periods of brain development is essential for optimized behavioral performance. We hypothesize that this mechanism is defective in fragile X syndrome (FXS), the leading heritable cause of intellectual disability and autism spectrum disorders. Here, we use optogenetic tools in the Drosophila FXS disease model to test activity-dependent dendritogenesis in two extrinsic neurons of the mushroom body (MB) learning and memory brain center: (1) the input projection neuron (PN) innervating Kenyon cells (KCs) in the MB calyx microglomeruli and (2) the output MVP2 neuron innervated by KCs in the MB peduncle. Both input and output neuron classes exhibit distinctive activity-dependent critical period dendritic remodeling. MVP2 arbors expand in Drosophila mutants null for fragile X mental retardation 1 (dfmr1), as well as following channelrhodopsin-driven depolarization during critical period development, but are reduced by halorhodopsin-driven hyperpolarization. Optogenetic manipulation of PNs causes the opposite outcome – reduced dendritic arbors following channelrhodopsin depolarization and expanded arbors following halorhodopsin hyperpolarization during development. Importantly, activity-dependent dendritogenesis in both neuron classes absolutely requires dfmr1 during one developmental window. These results show that dfmr1 acts in a neuron type-specific activity-dependent manner for sculpting dendritic arbors during early-use, critical period development of learning and memory circuitry in the Drosophila brain. PMID:25804740

  15. A spinal opsin controls early neural activity and drives a behavioral light response

    PubMed Central

    Friedmann, Drew; Hoagland, Adam; Berlin, Shai; Isacoff, Ehud Y.

    2014-01-01

    Non-visual detection of light by the vertebrate hypothalamus, pineal, and retina is known to govern seasonal and circadian behaviors [1]. However, the expression of opsins in multiple other brain structures [2–4] suggests a more expansive repertoire for light-regulation of physiology, behavior, and development. Translucent zebrafish embryos express extra-retinal opsins early on [5, 6], at a time when spontaneous activity in the developing central nervous system plays a role in neuronal maturation and circuit formation [7]. Though the presence of extra-retinal opsins is well documented, the function of direct photoreception by the central nervous system remains largely unknown. Here we show that early activity in the zebrafish spinal central pattern generator (CPG) and the earliest locomotory behavior are dramatically inhibited by physiological levels of environmental light. We find that the photo-sensitivity of this circuit is conferred by vertebrate ancient long opsin (VALopA), which we show to be a Gαi-coupled receptor that is expressed in the neurons of the spinal network. Sustained photo-activation of VALopA not only suppresses spontaneous activity but also alters the maturation of time-locked correlated network patterns. These results uncover a novel role for non-visual opsins and a mechanism for environmental regulation of spontaneous motor behavior and neural activity in a circuit previously thought to be governed only by intrinsic developmental programs. PMID:25484291

  16. Modulation of neural activity by reward in medial intraparietal cortex is sensitive to temporal sequence of reward

    PubMed Central

    Rajalingham, Rishi; Stacey, Richard Greg; Tsoulfas, Georgios

    2014-01-01

    To restore movements to paralyzed patients, neural prosthetic systems must accurately decode patients' intentions from neural signals. Despite significant advancements, current systems are unable to restore complex movements. Decoding reward-related signals from the medial intraparietal area (MIP) could enhance prosthetic performance. However, the dynamics of reward sensitivity in MIP is not known. Furthermore, reward-related modulation in premotor areas has been attributed to behavioral confounds. Here we investigated the stability of reward encoding in MIP by assessing the effect of reward history on reward sensitivity. We recorded from neurons in MIP while monkeys performed a delayed-reach task under two reward schedules. In the variable schedule, an equal number of small- and large-rewards trials were randomly interleaved. In the constant schedule, one reward size was delivered for a block of trials. The memory period firing rate of most neurons in response to identical rewards varied according to schedule. Using systems identification tools, we attributed the schedule sensitivity to the dependence of neural activity on the history of reward. We did not find schedule-dependent behavioral changes, suggesting that reward modulates neural activity in MIP. Neural discrimination between rewards was less in the variable than in the constant schedule, degrading our ability to decode reach target and reward simultaneously. The effect of schedule was mitigated by adding Haar wavelet coefficients to the decoding model. This raises the possibility of multiple encoding schemes at different timescales and reinforces the potential utility of reward information for prosthetic performance. PMID:25008408

  17. Global Mittag-Leffler synchronization of fractional-order neural networks with discontinuous activations.

    PubMed

    Ding, Zhixia; Shen, Yi; Wang, Leimin

    2016-01-01

    This paper is concerned with the global Mittag-Leffler synchronization for a class of fractional-order neural networks with discontinuous activations (FNNDAs). We give the concept of Filippov solution for FNNDAs in the sense of Caputo's fractional derivation. By using a singular Gronwall inequality and the properties of fractional calculus, the existence of global solution under the framework of Filippov for FNNDAs is proved. Based on the nonsmooth analysis and control theory, some sufficient criteria for the global Mittag-Leffler synchronization of FNNDAs are derived by designing a suitable controller. The proposed results enrich and enhance the previous reports. Finally, one numerical example is given to demonstrate the effectiveness of the theoretical results. PMID:26562442

  18. Repetition-Related Reductions in Neural Activity during Emotional Simulations of Future Events

    PubMed Central

    2015-01-01

    Simulations of future experiences are often emotionally arousing, and the tendency to repeatedly simulate negative future outcomes has been identified as a predictor of the onset of symptoms of anxiety. Nonetheless, next to nothing is known about how the healthy human brain processes repeated simulations of emotional future events. In this study, we present a paradigm that can be used to study repeated simulations of the emotional future in a manner that overcomes phenomenological confounds between positive and negative events. The results show that pulvinar nucleus and orbitofrontal cortex respectively demonstrate selective reductions in neural activity in response to frequently as compared to infrequently repeated simulations of negative and positive future events. Implications for research on repeated simulations of the emotional future in both non-clinical and clinical populations are discussed. PMID:26390294

  19. The role of shared neural activations, mirror neurons, and morality in empathy--a critical comment.

    PubMed

    Lamm, Claus; Majdandžić, Jasminka

    2015-01-01

    In the last decade, the phenomenon of empathy has received widespread attention by the field of social neuroscience. This has provided fresh insights for theoretical models of empathy, and substantially influenced the academic and public conceptions about this complex social skill. The present paper highlights three key issues which are often linked to empathy, but which at the same time might obscure our understanding of it. These issues are: (1) shared neural activations and whether these can be interpreted as evidence for simulation accounts of empathy; (2) the causal link of empathy to our presumed mirror neuron system; and (3) the question whether increasing empathy will result in better moral decisions and behaviors. The aim of our review is to provide the basis for critically evaluating our current understanding of empathy, and its public reception, and to inspire new research directions. PMID:25455743

  20. Variations in prestimulus neural activity predict the emotion-enhanced memory effect.

    PubMed

    Yick, Yee Ying; Buratto, Luciano G; Schaefer, Alexandre

    2016-08-01

    Here, we report evidence that electrophysiological neural activity preceding the onset of emotional pictures can predict whether they will be remembered or forgotten 24 h later, whereas the same effect was not observed for neutral pictures. In contrast to previous research, we observed this effect using a paradigm in which participants could not predict the emotional or the neutral content of the pictures before their onset. These effects were obtained alongside significant behavioural effects of superior recognition memory for emotional compared with neutral items. These findings suggest that the preferential encoding of emotional events in memory is determined by fluctuations in the availability of processing resources just before event onset. This explanation argues in favour of mediational models of emotional memory, which contend that emotional information is preferentially encoded because it mobilizes a greater amount of processing resources than neutral information. PMID:27295027

  1. Attentional Dissociation in Hypnosis And Neural Connectivity: Preliminary Evidence from Bilateral Electrodermal Activity.

    PubMed

    Bob, Petr; Siroka, Ivana

    2016-01-01

    According to recent findings, interhemispheric interactions and information connectivity represent crucial mechanisms used in processing information across various sensory modalities. To study these interactions, the authors measured bilateral electrodermal activity (EDA) in 33 psychiatric outpatients. The results show that, during congruent Stroop stimuli in hypnosis, the patients with higher hypnotizability manifest a decreased level of interhemispheric information transfer measured by pointwise transinformation (PTI) that was calculated from left and right EDA records. These results show that specific shifts of attentional focus during hypnosis are related to changes of interhemispheric interactions that may be reflected in neural connectivity calculated from the bilateral EDA measurement. This attentional shift may cause dissociated attentional control disturbing integrative functions of consciousness and contextual experiences. PMID:27267677

  2. Adipose Tissue and Energy Expenditure: Central and Peripheral Neural Activation Pathways.

    PubMed

    Blaszkiewicz, Magdalena; Townsend, Kristy L

    2016-06-01

    Increasing energy expenditure is an appealing therapeutic target for the prevention and reversal of metabolic conditions such as obesity or type 2 diabetes. However, not enough research has investigated how to exploit pre-existing neural pathways, both in the central nervous system (CNS) and peripheral nervous system (PNS), in order to meet these needs. Here, we review several research areas in this field, including centrally acting pathways known to drive the activation of sympathetic nerves that can increase lipolysis and browning in white adipose tissue (WAT) or increase thermogenesis in brown adipose tissue (BAT), as well as other central and peripheral pathways able to increase energy expenditure of these tissues. In addition, we describe new work investigating the family of transient receptor potential (TRP) channels on metabolically important sensory nerves, as well as the role of the vagus nerve in regulating energy balance. PMID:27055864

  3. A hardware-based computational platform for Generalized Laguerre-Volterra MIMO model for neural activities.

    PubMed

    Li, Will X Y; Chan, Rosa H M; Zhang, Wei; Cheung, Ray C C; Song, Dong; Berger, Theodore W

    2011-01-01

    A parallelized and pipelined architecture based on FPGA and a higher-level Self Reconfiguration Platform are proposed in this paper to model Generalized Laguerre-Volterra MIMO system essential in identifying the time-varying neural dynamics underlying spike activities. Our proposed design is based on the Xilinx Virtex-6 FPGA platform and the processing core can produce data samples at a speed of 1.33 × 10(6)/s, which is 3.1 × 10(3) times faster than the corresponding C model running on an Intel i7-860 Quad Core Processor. The ongoing work of the construction of the advanced Self Reconfiguration Platform is presented and initial test results are provided. PMID:22256020

  4. Fluctuations in nuclear envelope's potential mediate synchronization of early neural activity

    SciTech Connect

    Yamashita, Masayuki

    2011-03-04

    Research highlights: {yields} Nuclear envelope's potential changes with a release of Ca{sup 2+}. {yields} Changes in nuclear envelope's potential underlie synchronous burst discharges. {yields} Nuclear envelope's potential generates periodic bursts of fluctuations. {yields} Fluctuations in nuclear envelope's potential function as a current noise generator. -- Abstract: Neural progenitor cells and developing neurons show periodic, synchronous Ca{sup 2+} rises even before synapse formation, and the origin of the synchronous activity remains unknown. Here, fluorescence measurement revealed that the membrane potential of the nuclear envelope, which forms an intracellular Ca{sup 2+} store, changed with a release of Ca{sup 2+} and generated spontaneous, periodic bursts of fluctuations in potential. Furthermore, changes in the nuclear envelope's potential underlay spike burst generations. These results support the model that voltage fluctuations of the nuclear envelope synchronize Ca{sup 2+} release between cells and also function as a current noise generator to cause synchronous burst discharges.

  5. Neural Response during the Activation of the Attachment System in Patients with Borderline Personality Disorder: An fMRI Study

    PubMed Central

    Buchheim, Anna; Erk, Susanne; George, Carol; Kächele, Horst; Martius, Philipp; Pokorny, Dan; Spitzer, Manfred; Walter, Henrik

    2016-01-01

    Individuals with borderline personality disorder (BPD) are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Eleven female patients with BPD without posttraumatic stress disorder (PTSD) and 17 healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System (AAP), an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for 2 min. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex (DLPFC) and the rostral cingulate zone (RCZ). We interpret this as a neural signature of BPD patients’ inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear. PMID:27531977

  6. Neural Response during the Activation of the Attachment System in Patients with Borderline Personality Disorder: An fMRI Study.

    PubMed

    Buchheim, Anna; Erk, Susanne; George, Carol; Kächele, Horst; Martius, Philipp; Pokorny, Dan; Spitzer, Manfred; Walter, Henrik

    2016-01-01

    Individuals with borderline personality disorder (BPD) are characterized by emotional instability, impaired emotion regulation and unresolved attachment patterns associated with abusive childhood experiences. We investigated the neural response during the activation of the attachment system in BPD patients compared to healthy controls using functional magnetic resonance imaging (fMRI). Eleven female patients with BPD without posttraumatic stress disorder (PTSD) and 17 healthy female controls matched for age and education were telling stories in the scanner in response to the Adult Attachment Projective Picture System (AAP), an eight-picture set assessment of adult attachment. The picture set includes theoretically-derived attachment scenes, such as separation, death, threat and potential abuse. The picture presentation order is designed to gradually increase the activation of the attachment system. Each picture stimulus was presented for 2 min. Analyses examine group differences in attachment classifications and neural activation patterns over the course of the task. Unresolved attachment was associated with increasing amygdala activation over the course of the attachment task in patients as well as controls. Unresolved controls, but not patients, showed activation in the right dorsolateral prefrontal cortex (DLPFC) and the rostral cingulate zone (RCZ). We interpret this as a neural signature of BPD patients' inability to exert top-down control under conditions of attachment distress. These findings point to possible neural mechanisms for underlying affective dysregulation in BPD in the context of attachment trauma and fear. PMID:27531977

  7. Chromosome Aberrations in Astronauts

    NASA Technical Reports Server (NTRS)

    George, Kerry A.; Durante, M.; Cucinotta, Francis A.

    2007-01-01

    A review of currently available data on in vivo induced chromosome damage in the blood lymphocytes of astronauts proves that, after protracted exposure of a few months or more to space radiation, cytogenetic biodosimetry analyses of blood collected within a week or two of return from space provides a reliable estimate of equivalent radiation dose and risk. Recent studies indicate that biodosimetry estimates from single spaceflights lie within the range expected from physical dosimetry and biophysical models, but very large uncertainties are associated with single individual measurements and the total sample population remains low. Retrospective doses may be more difficult to estimate because of the fairly rapid time-dependent loss of "stable" aberrations in blood lymphocytes. Also, biodosimetry estimates from individuals who participate in multiple missions, or very long (interplanetary) missions, may be complicated by an adaptive response to space radiation and/or changes in lymphocyte survival and repopulation. A discussion of published data is presented and specific issues related to space radiation biodosimetry protocols are discussed.

  8. Activity-dependent plasticity in the isolated embryonic avian brainstem following manipulations of rhythmic spontaneous neural activity.

    PubMed

    Vincen-Brown, Michael A; Revill, Ann L; Pilarski, Jason Q

    2016-07-15

    When rhythmic spontaneous neural activity (rSNA) first appears in the embryonic chick brainstem and cranial nerve motor axons it is principally driven by nicotinic neurotransmission (NT). At this early age, the nicotinic acetylcholine receptor (nAChR) agonist nicotine is known to critically disrupt rSNA at low concentrations (0.1-0.5μM), which are levels that mimic the blood plasma levels of a fetus following maternal cigarette smoking. Thus, we quantified the effect of persistent exposure to exogenous nicotine on rSNA using an in vitro developmental model. We found that rSNA was eliminated by continuous bath application of exogenous nicotine, but rSNA recovered activity within 6-12h despite the persistent activation and desensitization of nAChRs. During the recovery period rSNA was critically driven by chloride-mediated membrane depolarization instead of nicotinic NT. To test whether this observed compensation was unique to the antagonism of nicotinic NT or whether the loss of spiking behavior also played a role, we eliminated rSNA by lowering overall excitatory drive with a low [K(+)]o superfusate. In this context, rSNA again recovered, although the recovery time was much quicker, and exhibited a lower frequency, higher duration, and an increase in the number of bursts per episode when compared to control embryos. Importantly, we show that the main compensatory response to lower overall excitatory drive, similar to nicotinergic block, is a result of potentiated chloride mediated membrane depolarization. These results support increasing evidence that early neural circuits sense spiking behavior to maintain primordial bioelectric rhythms. Understanding the nature of developmental plasticity in the nervous system, especially versions that preserve rhythmic behaviors following clinically meaningful environmental stimuli, both normal and pathological, will require similar studies to determine the consequences of feedback compensation at more mature chronological ages

  9. A method for locating regions containing neural activation at a given confidence level from MEG data

    SciTech Connect

    Schmidt, D.M.; George, J.S.

    1996-02-01

    The MEG inverse problem does not have a general, unique solution. Unless restrictive model assumptions are made, there are generally many more free parameters than measurements and there exist silent sources - current distributions which produce no external magnetic field. By weighting solutions according to how well each fits our prior notion about what properties good solutions should have, it may be possible to obtain a single current distribution that best fits the data and our expectations. However, in general there will still exist a number of different current distributions which fit both the data and our prior expectations sufficiently well. For example, a simulated data set based on a single or several dipoles can generally be fit equally well by a distributed current minimum-norm reconstruction. In experimental data it is often possible to find a relatively small number of dipoles which both fit the data and have a norm not much larger than that of the minimum-norm solution. Moreover, the few-dipole solutions often have currents in different regions than the corresponding minimum-norm solution. Because there exist well-fitting current distributions which may have current in significantly different locations, it can be misleading to infer locations of stimulus-correlated neural activity based on a single, best-fitting current distribution. we demonstrate here a method for inferring the location and number of regions containing neural activation by considering all possible current distributions within a given model (not just the most likely one) weighted according to how well each fits both the data and our prior expectations.

  10. Neural activity patterns evoked by a spouse's incongruent emotional reactions when recalling marriage-relevant experiences.

    PubMed

    Petrican, Raluca; Rosenbaum, Rachel Shayna; Grady, Cheryl

    2015-10-01

    Resonance with the inner states of another social actor is regarded as a hallmark of emotional closeness. Nevertheless, sensitivity to potential incongruities between one's own and an intimate partner's subjective experience is reportedly also important for close relationship quality. Here, we tested whether perceivers show greater neurobehavioral responsiveness to a spouse's positive (rather than negative) context-incongruent emotions, and whether this effect is influenced by the perceiver's satisfaction with the relationship. Thus, we used fMRI to scan older long-term married female perceivers while they judged either their spouse's or a stranger's affect, based on incongruent nonverbal and verbal cues. The verbal cues were selected to evoke strongly polarized affective responses. Higher perceiver marital satisfaction predicted greater neural processing of the spouse's (rather than the strangers) nonverbal cues. Nevertheless, across all perceivers, greater neural processing of a spouse's (rather than a stranger's) nonverbal behavior was reliably observed only when the behavior was positive and the context was negative. The spouse's positive (rather than negative) nonverbal behavior evoked greater activity in putative mirror neuron areas, such as the bilateral inferior parietal lobule (IPL). This effect was related to a stronger inhibitory influence of cognitive control areas on mirror system activity in response to a spouse's negative nonverbal cues, an effect that strengthened with increasing perceiver marital satisfaction. Our valence-asymmetric findings imply that neurobehavioral responsiveness to a close other's emotions may depend, at least partly, on cognitive control resources, which are used to support the perceiver's interpersonal goals (here, goals that are relevant to relationship stability). PMID:26219536

  11. Activational and effort-related aspects of motivation: neural mechanisms and implications for psychopathology.

    PubMed

    Salamone, John D; Yohn, Samantha E; López-Cruz, Laura; San Miguel, Noemí; Correa, Mercè

    2016-05-01

    Motivation has been defined as the process that allows organisms to regulate their internal and external environment, and control the probability, proximity and availability of stimuli. As such, motivation is a complex process that is critical for survival, which involves multiple behavioural functions mediated by a number of interacting neural circuits. Classical theories of motivation suggest that there are both directional and activational aspects of motivation, and activational aspects (i.e. speed and vigour of both the instigation and persistence of behaviour) are critical for enabling organisms to overcome work-related obstacles or constraints that separate them from significant stimuli. The present review discusses the role of brain dopamine and related circuits in behavioural activation, exertion of effort in instrumental behaviour, and effort-related decision-making, based upon both animal and human studies. Impairments in behavioural activation and effort-related aspects of motivation are associated with psychiatric symptoms such as anergia, fatigue, lassitude and psychomotor retardation, which cross multiple pathologies, including depression, schizophrenia, and Parkinson's disease. Therefore, this review also attempts to provide an interdisciplinary approach that integrates findings from basic behavioural neuroscience, behavioural economics, clinical neuropsychology, psychiatry, and neurology, to provide a coherent framework for future research and theory in this critical field. Although dopamine systems are a critical part of the brain circuitry regulating behavioural activation, exertion of effort, and effort-related decision-making, mesolimbic dopamine is only one part of a distributed circuitry that includes multiple neurotransmitters and brain areas. Overall, there is a striking similarity between the brain areas involved in behavioural activation and effort-related processes in rodents and in humans. Animal models of effort-related decision

  12. The Neural Signature of Subliminal Visuomotor Priming: Brain Activity and Functional Connectivity Profiles.

    PubMed

    Ulrich, Martin; Kiefer, Markus

    2016-06-01

    Unconscious visuomotor priming defined as the advantage in reaction time (RT) or accuracy for target shapes mapped to the same (congruent condition) when compared with a different (incongruent condition) motor response as a preceding subliminally presented prime shape has been shown to modulate activity within a visuomotor network comprised of parietal and frontal motor areas in previous functional magnetic resonance imaging (fMRI) studies. The present fMRI study investigated whether, in addition to changes in brain activity, unconscious visuomotor priming results in a modulation of functional connectivity profiles. Activity associated with congruent compared with incongruent trials was lower in the bilateral inferior and medial superior frontal gyri, in the inferior parietal lobules, and in the right caudate nucleus and adjacent portions of the thalamus. Functional connectivity increased under congruent relative to incongruent conditions between ventral visual stream areas (e.g., calcarine, fusiform, and lingual gyri), the precentral gyrus, the supplementary motor area, posterior parietal areas, the inferior frontal gyrus, and the caudate nucleus. Our findings suggest that an increase in coupling between visuomotor regions, reflecting higher efficiency of processing, is an important neural mechanism underlying unconscious visuomotor priming, in addition to changes in the magnitude of activation. PMID:25858968

  13. Neural activation abnormalities during self-referential processing in schizophrenia: an fMRI study.

    PubMed

    Liu, Jiacheng; Corbera, Silvia; Wexler, Bruce Edward

    2014-06-30

    Impairments in self-awareness contribute to disability in schizophrenia. Studies have revealed activation abnormalities in schizophrenia in cortical midline structures associated with self-reference. We used functional magnetic resonance imaging to compare activation throughout the brain in people with schizophrenia and healthy controls (Kelly et al., 2002) while they indicated whether trait adjectives described attributes of themselves, their mother or a former president of the United States. Blood oxygenation level dependent signal in each condition was compared to resting fixation. Patients were less likely and slower to endorse positive self-attributes, and more likely and quicker to endorse negative self-attributes than controls. Activation abnormalities reported previously in cortical midline structures were again noted. In addition, patients showed greater signal increases in frontal, temporal gyri and insula, and smaller signal decreases in posterior regions than healthy controls when thinking about themselves. Group differences were less evident when subjects were thinking about their mothers and tended to go in the opposite direction when thinking about a president. Many of the areas showing abnormality have been shown in other studies to differ between patients and controls in structure and with other activation paradigms. We suggest that general neuropathology in schizophrenia alters the neural system configurations associated with self-representation. PMID:24795158

  14. Effects of negative air ions on activity of neural substrates involved in autonomic regulation in rats

    NASA Astrophysics Data System (ADS)

    Suzuki, Satoko; Yanagita, Shinya; Amemiya, Seiichiro; Kato, Yumi; Kubota, Natsuko; Ryushi, Tomoo; Kita, Ichiro

    2008-07-01

    The neural mechanism by which negative air ions (NAI) mediate the regulation of autonomic nervous system activity is still unknown. We examined the effects of NAI on physiological responses, such as blood pressure (BP), heart rate (HR), and heart rate variability (HRV) as well as neuronal activity, in the paraventricular nucleus of the hypothalamus (PVN), locus coeruleus (LC), nucleus ambiguus (NA), and nucleus of the solitary tract (NTS) with c-Fos immunohistochemistry in anesthetized, spontaneously breathing rats. In addition, we performed cervical vagotomy to reveal the afferent pathway involved in mediating the effects of NAI on autonomic regulation. NAI significantly decreased BP and HR, and increased HF power of the HRV spectrum. Significant decreases in c-Fos positive nuclei in the PVN and LC, and enhancement of c-Fos expression in the NA and NTS were induced by NAI. After vagotomy, these physiological and neuronal responses to NAI were not observed. These findings suggest that NAI can modulate autonomic regulation through inhibition of neuronal activity in PVN and LC as well as activation of NA neurons, and that these effects of NAI might be mediated via the vagus nerves.

  15. Hoarding disorder and obsessive-compulsive disorder show different patterns of neural activity during response inhibition

    PubMed Central

    Tolin, David F.; Witt, Suzanne T.; Stevens, Michael C.

    2014-01-01

    Although hoarding disorder (HD) has been historically conceptualized as a subtype or dimension of obsessive-compulsive disorder (OCD), preliminary evidence suggests that these two disorders have distinct neural underpinnings. The aim of the present study was to compare the hemodynamic responses of HD patients, OCD patients, and healthy controls (HC) during response inhibition on a high-conflict Go/NoGo task that has previously proved sensitive to OCD. Participants comprised 24 HD patients, 24 OCD patients, and 24 HCs who completed a Go/NoGo task during functional magnetic resonance imaging (fMRI). Although behavioral data showed no difference among the groups in Go/NoGo task performance, significant differences in hemodynamic activity were noted. During correct rejects (successful response inhibition), HD patients showed greater right precentral gyrus activation, whereas OCD patients exhibited greater right orbitofrontal activation, as assessed using a region of interest approach. During errors of commission (response inhibition failures), OCD patients, but not HD patients, were characterized by excessive activity in left and right orbitofrontal gyrus. The present results lend further support to the biological distinction between HD and OCD, and they are consistent with previous research suggesting frontal hypoactivity in HD patients during hoarding-unrelated tasks. PMID:24389161

  16. Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation.

    PubMed

    Rhee, Yong-Hee; Yi, Sang-Hoon; Kim, Joo Yeon; Chang, Mi-Yoon; Jo, A-Young; Kim, Jinyoung; Park, Chang-Hwan; Cho, Je-Yoel; Choi, Young-Jin; Sun, Woong; Lee, Sang-Hun

    2016-01-01

    The intracellular Raf-Erk signaling pathway is activated during neural stem cell (NSC) proliferation, and neuronal and astrocytic differentiation. A key question is how this signal can evoke multiple and even opposing NSC behaviors. We show here, using a constitutively active Raf (ca-Raf), that Raf-Erk activation in NSCs induces neuronal differentiation in a cell-autonomous manner. By contrast, it causes NSC proliferation and the formation of astrocytes in an extrinsic autocrine/paracrine manner. Thus, treatment of NSCs with medium (CM) conditioned in ca-Raf-transduced NSCs (Raf-CM; RCM) became activated to form proliferating astrocytes resembling radial glial cells (RGCs) or adult-type NSCs. Infusion of Raf-CM into injured mouse brains caused expansion of the NSC population in the subventricular zone, followed by the formation of new neurons that migrated to the damaged site. Our study shows an example how molecular mechanisms dissecting NSC behaviors can be utilized to develop regenerative therapies in brain disorders. PMID:27554447

  17. Wrestling model of the repertoire of activity propagation modes in quadruple neural networks.

    PubMed

    Shteingart, Hanan; Raichman, Nadav; Baruchi, Itay; Ben-Jacob, Eshel

    2010-01-01

    The spontaneous activity of engineered quadruple cultured neural networks (of four-coupled sub-networks) exhibits a repertoire of different types of mutual synchronization events. Each event corresponds to a specific activity propagation mode (APM) defined by the order of activity propagation between the sub-networks. We statistically characterized the frequency of spontaneous appearance of the different types of APMs. The relative frequencies of the APMs were then examined for their power-law properties. We found that the frequencies of appearance of the leading (most frequent) APMs have close to constant algebraic ratio reminiscent of Zipf's scaling of words. We show that the observations are consistent with a simplified "wrestling" model. This model represents an extension of the "boxing arena" model which was previously proposed to describe the ratio between the two activity modes in two coupled sub-networks. The additional new element in the "wrestling" model presented here is that the firing within each network is modeled by a time interval generator with similar intra-network Lévy distribution. We modeled the different burst-initiation zones' interaction by competition between the stochastic generators with Gaussian inter-network variability. Estimation of the model parameters revealed similarity across different cultures while the inter-burst-interval of the cultures was similar across different APMs as numerical simulation of the model predicts. PMID:20890451

  18. Neural stem cells secrete factors facilitating brain regeneration upon constitutive Raf-Erk activation

    PubMed Central

    Rhee, Yong-Hee; Yi, Sang-Hoon; Kim, Joo Yeon; Chang, Mi-Yoon; Jo, A-Young; Kim, Jinyoung; Park, Chang-Hwan; Cho, Je-Yoel; Choi, Young-Jin; Sun, Woong; Lee, Sang-Hun

    2016-01-01

    The intracellular Raf-Erk signaling pathway is activated during neural stem cell (NSC) proliferation, and neuronal and astrocytic differentiation. A key question is how this signal can evoke multiple and even opposing NSC behaviors. We show here, using a constitutively active Raf (ca-Raf), that Raf-Erk activation in NSCs induces neuronal differentiation in a cell-autonomous manner. By contrast, it causes NSC proliferation and the formation of astrocytes in an extrinsic autocrine/paracrine manner. Thus, treatment of NSCs with medium (CM) conditioned in ca-Raf-transduced NSCs (Raf-CM; RCM) became activated to form proliferating astrocytes resembling radial glial cells (RGCs) or adult-type NSCs. Infusion of Raf-CM into injured mouse brains caused expansion of the NSC population in the subventricular zone, followed by the formation of new neurons that migrated to the damaged site. Our study shows an example how molecular mechanisms dissecting NSC behaviors can be utilized to develop regenerative therapies in brain disorders. PMID:27554447

  19. Differential frequency modulation of neural activity in the lateral cerebellar nucleus in failed and successful grasps.

    PubMed

    Cooperrider, Jessica; Gale, John T; Gopalakrishnan, Raghavan; Chan, Hugh H; Wathen, Connor; Park, Hyun-Joo; Baker, Kenneth B; Shaikh, Aasef G; Machado, Andre G

    2016-03-01

    The olivo-cerebellar system has an essential role in the detection and adaptive correction of movement errors. While there is evidence of an error signal in the cerebellar cortex and inferior olivary nucleus, the deep cerebellar nuclei have been less thoroughly investigated. Here, we recorded local field potential activity in the rodent lateral cerebellar nucleus during a skilled reaching task and compared event-related changes in neural activity between unsuccessful and successful attempts. Increased low gamma (40-50 Hz) band power was present throughout the reach and grasp behavior, with no difference between successful and unsuccessful trials. Beta band (12-30 Hz) power, however, was significantly increased in unsuccessful reaches, compared to successful, throughout the trial, including during the epoch preceding knowledge of the trial's outcome. This beta band activity was greater in unsuccessful trials of high-performing days, compared to unsuccessful trials of low-performing days, indicating that this activity may reflect an error prediction signal, developed over the course of motor learning. These findings suggest an error-related discriminatory oscillatory hallmark of movement in the deep cerebellar nuclei. PMID:26698925

  20. Classification of human activity on water through micro-Dopplers using deep convolutional neural networks

    NASA Astrophysics Data System (ADS)

    Kim, Youngwook; Moon, Taesup

    2016-05-01

    Detecting humans and classifying their activities on the water has significant applications for surveillance, border patrols, and rescue operations. When humans are illuminated by radar signal, they produce micro-Doppler signatures due to moving limbs. There has been a number of research into recognizing humans on land by their unique micro-Doppler signatures, but there is scant research into detecting humans on water. In this study, we investigate the micro-Doppler signatures of humans on water, including a swimming person, a swimming person pulling a floating object, and a rowing person in a small boat. The measured swimming styles were free stroke, backstroke, and breaststroke. Each activity was observed to have a unique micro-Doppler signature. Human activities were classified based on their micro-Doppler signatures. For the classification, we propose to apply deep convolutional neural networks (DCNN), a powerful deep learning technique. Rather than using conventional supervised learning that relies on handcrafted features, we present an alternative deep learning approach. We apply the DCNN, one of the most successful deep learning algorithms for image recognition, directly to a raw micro-Doppler spectrogram of humans on the water. Without extracting any explicit features from the micro-Dopplers, the DCNN can learn the necessary features and build classification boundaries using the training data. We show that the DCNN can achieve accuracy of more than 87.8% for activity classification using 5- fold cross validation.

  1. Correction of Distributed Optical Aberrations

    SciTech Connect

    Baker, K; Olivier, S; Carrano, C; Phillion, D

    2006-02-12

    The objective of this project was to demonstrate the use of multiple distributed deformable mirrors (DMs) to improve the performance of optical systems with distributed aberrations. This concept is expected to provide dramatic improvement in the optical performance of systems in applications where the aberrations are distributed along the optical path or within the instrument itself. Our approach used multiple actuated DMs distributed to match the aberration distribution. The project developed the algorithms necessary to determine the required corrections and simulate the performance of these multiple DM systems.

  2. Coating-induced wavefront aberrations

    NASA Astrophysics Data System (ADS)

    Reiley, Daniel J.; Chipman, Russell A.

    1992-12-01

    The coatings which are used on telescope mirrors and other optical interfaces can have a profound effect on the image quality formed by an optical system. This paper evaluates the defocus and astigmatism which are caused by the s- and p-phase shifts of coatings. These coating-induced wavefront aberrations are usually insignificant, but can, under certain circumstances, overshadow the geometric wavefront aberrations of the system. The wavefront aberrations induced by reflection-enhanced coatings on an f/1.5 Cassegrain telescope are numerically evaluated as an example.

  3. Optical Neural Interfaces

    PubMed Central

    Warden, Melissa R.; Cardin, Jessica A.; Deisseroth, Karl

    2014-01-01

    Genetically encoded optical actuators and indicators have changed the landscape of neuroscience, enabling targetable control and readout of specific components of intact neural circuits in behaving animals. Here, we review the development of optical neural interfaces, focusing on hardware designed for optical control of neural activity, integrated optical control and electrical readout, and optical readout of population and single-cell neural activity in freely moving mammals. PMID:25014785

  4. Evaluation of neural reflex activation as a mode of action for the acute respiratory effects of ozone.

    PubMed

    Prueitt, Robyn L; Goodman, Julie E

    2016-09-01

    Exposure to elevated levels of ozone has been associated with a variety of respiratory-related health endpoints in both epidemiology and controlled human exposure studies, including lung function decrements and airway inflammation. A mode of action (MoA) for these effects has not been established, but it has been proposed that they may occur through ozone-induced activation of neural reflexes. We critically reviewed experimental studies of ozone exposure and neural reflex activation and applied the International Programme on Chemical Safety (IPCS) mode-of-action/human relevance framework to evaluate the biological plausibility and human relevance of this proposed MoA. Based on the currently available experimental data, we found that the proposed MoA of neural reflex activation is biologically plausible for the endpoint of ozone-induced lung function decrements at high ozone exposures, but further studies are needed to fill important data gaps regarding the relevance of this MoA at lower exposures. A role for the proposed MoA in ozone-induced airway inflammation is less plausible, as the evidence is conflicting and is also of unclear relevance given the lack of studies conducted at lower exposures. The evidence suggests a different MoA for ozone-induced inflammation that may still be linked to the key events in the proposed MoA, such that neural reflex activation may have some degree of involvement in modulating ozone-induced neutrophil influx, even if it is not a direct role. PMID:27569521

  5. Neural pathways that mediate the effects of afferent stimuli on paraventricular nucleus multiunit activity in freely moving rats.

    PubMed

    Mor, G; Saphier, D; Feldman, S

    1987-01-01

    The direct involvement of the hypothalamic paraventricular nucleus (PVN) in the control of adrenocortical secretion is now generally accepted. In order to contribute to our understanding of the electrical activity of cells in this region during adrenocortical activation, we have recorded multiunit electrical activity (MUA) in response to acute neural stimuli in freely moving male rats and have examined the pathways involved. Photic, acoustic, olfactory, and sciatic nerve stimulation all increased PVN MUA by between 130% and 250%. These responses were selectively blocked, according to the stimulus modality tested, by radiofrequency lesions of central neural structures. Thus PVN responses to photic stimulation were blocked by lesions of the suprachiasmatic nuclei and reduced by mammillary peduncle lesions but were unaffected by lesions of the bed nuclei of the stria terminalis. Responses to acoustic stimulation were blocked by lesions of the mammillary peduncles but not by those placed in the suprachiasmatic nuclei, the septum, or the bed nuclei of the stria terminalis. Lesions of the septum blocked the response to sciatic nerve stimulation but did not affect the response to olfactory stimulation with amyl acetate fumes, which was blocked by lesions of the bed nuclei of the stria terminalis. The data confirm those obtained in endocrine studies concerning the neural pathways involved in the transmission of neural stimuli that produce adrenocortical activation. PMID:3625806

  6. The Effects of Simulated Stuttering and Prolonged Speech on the Neural Activation Patterns of Stuttering and Nonstuttering Adults

    ERIC Educational Resources Information Center

    De Nil, Luc F.; Beal, Deryk S.; Lafaille, Sophie J.; Kroll, Robert M.; Crawley, Adrian P.; Gracco, Vincent L.

    2008-01-01

    Functional magnetic resonance imaging was used to investigate the neural correlates of passive listening, habitual speech and two modified speech patterns (simulated stuttering and prolonged speech) in stuttering and nonstuttering adults. Within-group comparisons revealed increased right hemisphere biased activation of speech-related regions…

  7. Meditation reduces pain-related neural activity in the anterior cingulate cortex, insula, secondary somatosensory cortex, and thalamus

    PubMed Central

    Nakata, Hiroki; Sakamoto, Kiwako; Kakigi, Ryusuke

    2014-01-01

    Recent studies have shown that meditation inhibits or relieves pain perception. To clarify the underlying mechanisms for this phenomenon, neuroimaging methods, such as functional magnetic resonance imaging, and neurophysiological methods, such as magnetoencephalography and electroencephalography, have been used. However, it has been difficult to interpret the results, because there is some paradoxical evidence. For example, some studies reported increased neural responses to pain stimulation during meditation in the anterior cingulate cortex (ACC) and insula, whereas others showed a decrease in these regions. There have been inconsistent findings to date. Moreover, in general, since the activities of the ACC and insula are correlated with pain perception, the increase in neural activities during meditation would be related to the enhancement of pain perception rather than its reduction. These contradictions might directly contribute to the ‘mystery of meditation.’ In this review, we presented previous findings for brain regions during meditation and the anatomical changes that occurred in the brain with long-term meditation training. We then discussed the findings of previous studies that examined pain-related neural activity during meditation. We also described the brain mechanisms responsible for pain relief during meditation, and possible reasons for paradoxical evidence among previous studies. By thoroughly overviewing previous findings, we hypothesized that meditation reduces pain-related neural activity in the ACC, insula, secondary somatosensory cortex, and thalamus. We suggest that the characteristics of the modulation of this activity may depend on the kind of meditation and/or number of years of experience of meditation, which were associated with paradoxical findings among previous studies that investigated pain-related neural activities during meditation. PMID:25566158

  8. Artificial neural network modelling of the antioxidant activity and phenolic compounds of bananas submitted to different drying treatments.

    PubMed

    Guiné, Raquel P F; Barroca, Maria João; Gonçalves, Fernando J; Alves, Mariana; Oliveira, Solange; Mendes, Mateus

    2015-02-01

    Bananas (cv. Musa nana and Musa cavendishii) fresh and dried by hot air at 50 and 70°C and lyophilisation were analysed for phenolic contents and antioxidant activity. All samples were subject to six extractions (three with methanol followed by three with acetone/water solution). The experimental data served to train a neural network adequate to describe the experimental observations for both output variables studied: total phenols and antioxidant activity. The results show that both bananas are similar and air drying decreased total phenols and antioxidant activity for both temperatures, whereas lyophilisation decreased the phenolic content in a lesser extent. Neural network experiments showed that antioxidant activity and phenolic compounds can be predicted accurately from the input variables: banana variety, dryness state and type and order of extract. Drying state and extract order were found to have larger impact in the values of antioxidant activity and phenolic compounds. PMID:25172734

  9. Analysis of cell identity, morphology, apoptosis and mitotic activity in a primary neural cell culture system in Drosophila

    PubMed Central

    2012-01-01

    In Drosophila, most neurogenetic research is carried out in vivo. Mammalian research demonstrates that primary cell culture techniques provide a powerful model to address cell autonomous and non-autonomous processes outside their endogenous environment. We developed a cell culture system in Drosophila using wildtype and genetically manipulated primary neural tissue for long-term observations. We assessed the molecular identity of distinct neural cell types by immunolabeling and genetically expressed fluorescent cell markers. We monitored mitotic activity of cell cultures derived from wildtype and tumorous larval brains. Our system provides a powerful approach to unveil developmental processes in the nervous system and to complement studies in vivo. PMID:22554060

  10. Almost periodic dynamical behaviors for generalized Cohen-Grossberg neural networks with discontinuous activations via differential inclusions

    NASA Astrophysics Data System (ADS)

    Wang, Dongshu; Huang, Lihong

    2014-10-01

    In this paper, we investigate the almost periodic dynamical behaviors for a class of general Cohen-Grossberg neural networks with discontinuous right-hand sides, time-varying and distributed delays. By means of retarded differential inclusions theory and nonsmooth analysis theory with generalized Lyapunov approach, we obtain the existence, uniqueness and global stability of almost periodic solution to the neural networks system. It is worthy to pointed out that, without assuming the boundedness or monotonicity of the discontinuous neuron activation functions, our results will also be valid. Finally, we give some numerical examples to show the applicability and effectiveness of our main results.

  11. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    NASA Astrophysics Data System (ADS)

    Secundo, Lavi

    , the correlation of ECoG activity to kinematic parameters of arm movement is context-dependent, an important constraint to consider in future development of BMI systems. The third chapter delves into a fundamental organizational principle of the primate motor system---cortical control of contralateral limb movements. However, ipsilateral motor areas also appear to play a role in the control of ipsilateral limb movements. Several studies in monkeys have shown that individual neurons in ipsilateral primary motor cortex (M1) may represent, on average, the direction of movements of the ipsilateral arm. Given the increasing body of evidence demonstrating that neural ensembles can reliably represent information with a high temporal resolution, here we characterize the distributed neural representation of ipsilateral upper limb kinematics in both monkey and man. In two macaque monkeys trained to perform center-out reaching movements, we found that the ensemble spiking activity in M1 could continuously represent ipsilateral limb position. We also recorded cortical field potentials from three human subjects and also consistently found evidence of a neural representation for ipsilateral movement parameters. Together, our results demonstrate the presence of a high-fidelity neural representation for ipsilateral movement and illustrates that it can be successfully incorporated into a brain-machine interface.

  12. Endothelin signaling activates Mef2c expression in the neural crest through a MEF2C-dependent positive-feedback transcriptional pathway.

    PubMed

    Hu, Jianxin; Verzi, Michael P; Robinson, Ashley S; Tang, Paul Ling-Fung; Hua, Lisa L; Xu, Shan-Mei; Kwok, Pui-Yan; Black, Brian L

    2015-08-15

    Endothelin signaling is essential for neural crest development, and dysregulated Endothelin signaling is associated with several neural crest-related disorders, including Waardenburg and other syndromes. However, despite the crucial roles of this pathway in neural crest development and disease, the transcriptional effectors directly activated by Endothelin signaling during neural crest development remain incompletely elucidated. Here, we establish that the MADS box transcription factor MEF2C is an immediate downstream transcriptional target and effector of Endothelin signaling in the neural crest. We show that Endothelin signaling activates Mef2c expression in the neural crest through a conserved enhancer in the Mef2c locus and that CRISPR-mediated deletion of this Mef2c neural crest enhancer from the mouse genome abolishes Endothelin induction of Mef2c expression. Moreover, we demonstrate that Endothelin signaling activates neural crest expression of Mef2c by de-repressing MEF2C activity through a Calmodulin-CamKII-histone deacetylase signaling cascade. Thus, these findings identify a MEF2C-dependent, positive-feedback mechanism for Endothelin induction and establish MEF2C as an immediate transcriptional effector and target of Endothelin signaling in the neural crest. PMID:26160899

  13. Historical aspects of aberration correction.

    PubMed

    Rose, Harald H

    2009-06-01

    A brief history of the development of direct aberration correction in electron microscopy is outlined starting from the famous Scherzer theorem established in 1936. Aberration correction is the long story of many seemingly fruitless efforts to improve the resolution of electron microscopes by compensating for the unavoidable resolution-limiting aberrations of round electron lenses over a period of 50 years. The successful breakthrough, in 1997, can be considered as a quantum step in electron microscopy because it provides genuine atomic resolution approaching the size of the radius of the hydrogen atom. The additional realization of monochromators, aberration-free imaging energy filters and spectrometers has been leading to a new generation of analytical electron microscopes providing elemental and electronic information about the object on an atomic scale. PMID:19254915

  14. Neurodifferentiating potential of 8-prenylnaringenin and related compounds in neural precursor cells and correlation with estrogen-like activity.

    PubMed

    Urmann, Corinna; Oberbauer, Eleni; Couillard-Després, Sébastien; Aigner, Ludwig; Riepl, Herbert

    2015-03-01

    Neurodegenerative diseases are an increasing burden for our ageing societies; there is an as yet unmet need for the development of effective therapies. Neurogenesis, i.e., the generation of new neurons in the adult brain from neural stem cells, has received increasing attention since it offers the potential for endogenous brain repair and functional regeneration. Adult neurogenesis is partially under the control of sex hormones such as estradiol, and boosting neurogenesis with estradiol in animals correlates with cognitive improvement. 8-Prenylnaringenin imitates as highly potent phytoestrogen the effects of estradiol. Here, we studied the potential of 8-prenylnaringenin, 6-prenylnaringenin, and related compounds on differentiation induction in vitro using neural precursor cells transiently transfected with a doublecortin promoter luciferase construct, which was recently shown to indicate neuronal fate and differentiation. The flavanones 8-prenylnaringenin and 6-prenylnaringenin showed slight activity in this assay but significant activity by immunostaining. Although the estrogen-like activities of 8-prenylnaringenin and 6-prenylnaringenin are very different, the activity in differentiation induction is similar. Interestingly, also some prenylflavonoids with extended prenyl groups, e.g., a geranyl group, showed increased differentiation activity, while estrogen-like activity is decreased. This allows the conclusion that estrogen-like activity of prenylflavanones does not correlate directly with the activity of differentiation induction in neural precursor cells. PMID:25714726

  15. Formation of cellular projections in neural progenitor cells depends on SK3 channel activity.

    PubMed

    Liebau, Stefan; Vaida, Bianca; Proepper, Christian; Grissmer, Stephan; Storch, Alexander; Boeckers, Tobias M; Dietl, Paul; Wittekindt, Oliver H

    2007-06-01

    Ion channels are potent modulators for developmental processes in progenitor cells. In a screening approach for different ion channels in neural progenitor cells (NPCs) we observed a 1-ethyl-2-benzimidazolinone (1-EBIO) activated inward current, which could be blocked by scyllatoxin (ScTX, IC50=2+/- 0.3 nmol/L). This initial evidence for the expression of the small conductance Ca2+ activated K+-channel SK3 was confirmed by the detection of SK3 transcripts and protein in NPCs. Interestingly, SK3 proteins were highly expressed in non-differentiated NPCs with a focused localization in lamellipodia as well as filopodial structures. The activation of SK3 channels using 1-EBIO lead to an immediate filopodial sprouting and the translocation of the protein into these novel filopodial protrusions. Both effects could be prevented by the pre-incubation of NPCs with ScTX. Our study gives first evidence that the formation and prolongation of filopodia in NPCs is, at least in part, effectively induced and regulated by SK3 channels. PMID:17459146

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

    PubMed

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

    2015-12-01

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

  17. Distinct neural activation patterns underlie economic decisions in high and low psychopathy scorers

    PubMed Central

    Almeida, Pedro R.; Ferreira-Santos, Fernando; Barbosa, Fernando; Marques-Teixeira, João; Marsh, Abigail A.

    2014-01-01

    Psychopathic traits affect social functioning and the ability to make adaptive decisions in social interactions. This study investigated how psychopathy affects the neural mechanisms that are recruited to make decisions in the ultimatum game. Thirty-five adult participants recruited from the community underwent functional magnetic resonance imaging scanning while they performed the ultimatum game under high and low cognitive load. Across load conditions, high psychopathy scorers rejected unfair offers in the same proportion as low scorers, but perceived them as less unfair. Among low scorers, the perceived fairness of offers predicted acceptance rates, whereas in high scorers no association was found. Imaging results revealed that responses in each group were associated with distinct patterns of brain activation, indicating divergent decision mechanisms. Acceptance of unfair offers was associated with dorsolateral prefrontal cortex activity in low scorers and ventromedial prefrontal cortex activity in high scorers. Overall, our findings point to distinct motivations for rejecting unfair offers in individuals who vary in psychopathic traits, with rejections in high psychopathy scorers being probably induced by frustration. Implications of these results for models of ventromedial prefrontal cortex dysfunction in psychopathy are discussed. PMID:23748499

  18. Adolescent-specific patterns of behavior and neural activity during social reinforcement learning

    PubMed Central

    Jones, Rebecca M.; Somerville, Leah H.; Li, Jian; Ruberry, Erika J.; Powers, Alisa; Mehta, Natasha; Dyke, Jonathan; Casey, BJ

    2014-01-01

    Humans are sophisticated social beings. Social cues from others are exceptionally salient, particularly during adolescence. Understanding how adolescents interpret and learn from variable social signals can provide insight into the observed shift in social sensitivity during this period. The current study tested 120 participants between the ages of 8 and 25 years on a social reinforcement learning task where the probability of receiving positive social feedback was parametrically manipulated. Seventy-eight of these participants completed the task during fMRI scanning. Modeling trial-by-trial learning, children and adults showed higher positive learning rates than adolescents, suggesting that adolescents demonstrated less differentiation in their reaction times for peers who provided more positive feedback. Forming expectations about receiving positive social reinforcement correlated with neural activity within the medial prefrontal cortex and ventral striatum across age. Adolescents, unlike children and adults, showed greater insular activity during positive prediction error learning and increased activity in the supplementary motor cortex and the putamen when receiving positive social feedback regardless of the expected outcome, suggesting that peer approval may motivate adolescents towards action. While different amounts of positive social reinforcement enhanced learning in children and adults, all positive social reinforcement equally motivated adolescents. Together, these findings indicate that sensitivity to peer approval during adolescence goes beyond simple reinforcement theory accounts and suggests possible explanations for how peers may motivate adolescent behavior. PMID:24550063

  19. Intersubject variability in fearful face processing: the link between behavior and neural activation.

    PubMed

    Doty, Tracy J; Japee, Shruti; Ingvar, Martin; Ungerleider, Leslie G

    2014-12-01

    Stimuli that signal threat show considerable variability in the extents to which they enhance behavior, even among healthy individuals. However, the neural underpinning of this behavioral variability is not well understood. By manipulating expectation of threat in an fMRI study of fearful versus neutral face categorization, we uncovered a network of areas underlying variability in threat processing in healthy adults. We explicitly altered expectations by presenting face images at three different expectation levels: 80 %, 50 %, and 20 %. Subjects were instructed to report as quickly and accurately as possible whether the face was fearful (signaled threat) or not. An uninformative cue preceded each face by 4 s. By taking the difference between reaction times (RTs) to fearful and neutral faces, we quantified an overall fear RT bias (i.e., faster to fearful than to neutral faces) for each subject. This bias correlated positively with late-trial fMRI activation (8 s after the face) during unexpected-fearful-face trials in bilateral ventromedial prefrontal cortex, the left subgenual cingulate cortex, and the right caudate nucleus, and correlated negatively with early-trial fMRI activation (4 s after the cue) during expected-neutral-face trials in bilateral dorsal striatum and the right ventral striatum. These results demonstrate that the variability in threat processing among healthy adults is reflected not only in behavior, but also in the magnitude of activation in medial prefrontal and striatal regions that appear to encode affective value. PMID:24841078

  20. Sustained neural activity to gaze and emotion perception in dynamic social scenes.

    PubMed

    Ulloa, José Luis; Puce, Aina; Hugueville, Laurent; George, Nathalie

    2014-03-01

    To understand social interactions, we must decode dynamic social cues from seen faces. Here, we used magnetoencephalography (MEG) to study the neural responses underlying the perception of emotional expressions and gaze direction changes as depicted in an interaction between two agents. Subjects viewed displays of paired faces that first established a social scenario of gazing at each other (mutual attention) or gazing laterally together (deviated group attention) and then dynamically displayed either an angry or happy facial expression. The initial gaze change elicited a significantly larger M170 under the deviated than the mutual attention scenario. At around 400 ms after the dynamic emotion onset, responses at posterior MEG sensors differentiated between emotions, and between 1000 and 2200 ms, left posterior sensors were additionally modulated by social scenario. Moreover, activity on right anterior sensors showed both an early and prolonged interaction between emotion and social scenario. These results suggest that activity in right anterior sensors reflects an early integration of emotion and social attention, while posterior activity first differentiated between emotions only, supporting the view of a dual route for emotion processing. Altogether, our data demonstrate that both transient and sustained neurophysiological responses underlie social processing when observing interactions between others. PMID:23202662

  1. Neural correlates of reduced awareness in instrumental activities of daily living in frontotemporal dementia.

    PubMed

    Amanzio, Martina; D'Agata, Federico; Palermo, Sara; Rubino, Elisa; Zucca, Milena; Galati, Antonello; Pinessi, Lorenzo; Castellano, Giancarlo; Rainero, Innocenzo

    2016-10-01

    A decline in instrumental activities of daily living has been described as the earliest functional deficit in patients with neurodegenerative disease. It embraces specific competencies such as: "recalling the date and telephone calls, orienting to new places, remembering the location of objects at home, understanding conversation and the plot of a movie, keeping belongings in order, doing mental calculations and handling money, remembering appointments and shopping lists and performing clerical work". Since changes in instrumental daily living activities are one of the descriptors of behavioural-variant frontotemporal dementia, we decided to investigate the neural correlates of a reduced awareness in this specific domain in twenty-three consecutive behavioural-variant frontotemporal dementia patients. Gray matter volume changes associated with a reduced awareness for the instrumental domain, assessed using a validated caregiver-patient discrepancy questionnaire, were examined. Interestingly, we found disabilities in instrumental daily living activities and a reduced awareness of these to be related to medial prefrontal cortex atrophy, where the mid-cingulate cortices, dorsal anterior insula and cuneous play an important role. Importantly, if the executive system does not function correctly, the comparator mechanism of action self-monitoring does not detect mismatches between the current and previous performance states stored in the personal database, and produces a reduced awareness for the instrumental domain. PMID:27534380

  2. Simultaneous all-optical manipulation and recording of neural circuit activity with cellular resolution in vivo

    PubMed Central

    Packer, Adam M.; Russell, Lloyd E.; Dalgleish, Henry W.P.; Häusser, Michael

    2016-01-01

    We describe an all-optical strategy for simultaneously manipulating and recording the activity of multiple neurons with cellular resolution in vivo. Concurrent two-photon optogenetic activation and calcium imaging is enabled by coexpression of a red-shifted opsin and a genetically encoded calcium indicator. A spatial light modulator allows tens of user-selected neurons to be targeted for spatiotemporally precise optogenetic activation, while simultaneous fast calcium imaging provides high-resolution network-wide readout of the manipulation with negligible optical crosstalk. Proof-of-principle experiments in mouse barrel cortex demonstrate interrogation of the same neuronal population during different behavioral states, and targeting of neuronal ensembles based on their functional signature. This approach extends the optogenetic toolkit beyond the specificity obtained with genetic or viral approaches, enabling high-throughput, flexible and long-term optical interrogation of functionally defined neural circuits with single-cell and single-spike resolution in the mammalian brain in vivo. PMID:25532138

  3. A neural network approach for on-line fault detection of nitrogen sensors in alternated active sludge treatment plants.

    PubMed

    Caccavale, F; Digiulio, P; Iamarino, M; Masi, S; Pierri, F

    2010-01-01

    In this paper, an effective strategy for fault detection of nitrogen sensors in alternated active sludge treatment plants is proposed and tested on a simulated set-up. It is based on two predictive neural networks, which are trained using a historical set of data collected during fault-free operation of a wastewater treatment plant and their ability to predict reduced (ammonium) and oxidized (nitrates and nitrites) nitrogen is tested. The neural networks are also characterized by good generalization ability and robustness with respect to the influent variability with time and weather conditions. Then, simulations have been carried out imposing different kinds of fault on both sensors, as isolated spikes, abrupt bias and increased noise. Processing of residuals, based on the difference between measured concentration values and neural networks predictions, allows a quick revealing of the fault as well as the isolation of the corrupted sensor. PMID:21123904

  4. 3D visual discomfort predictor: analysis of horizontal disparity and neural activity statistics.

    PubMed

    Park, Jincheol; Oh, Heeseok; Lee, Sanghoon; Bovik, Alan Conrad

    2015-03-01

    Being able to predict the degree of visual discomfort that is felt when viewing stereoscopic 3D (S3D) images is an important goal toward ameliorating causative factors, such as excessive horizontal disparity, misalignments or mismatches between the left and right views of stereo pairs, or conflicts between different depth cues. Ideally, such a model should account for such factors as capture and viewing geometries, the distribution of disparities, and the responses of visual neurons. When viewing modern 3D displays, visual discomfort is caused primarily by changes in binocular vergence while accommodation in held fixed at the viewing distance to a flat 3D screen. This results in unnatural mismatches between ocular fixations and ocular focus that does not occur in normal direct 3D viewing. This accommodation vergence conflict can cause adverse effects, such as headaches, fatigue, eye strain, and reduced visual ability. Binocular vision is ultimately realized by means of neural mechanisms that subserve the sensorimotor control of eye movements. Realizing that the neuronal responses are directly implicated in both the control and experience of 3D perception, we have developed a model-based neuronal and statistical framework called the 3D visual discomfort predictor (3D-VDP)that automatically predicts the level of visual discomfort that is experienced when viewing S3D images. 3D-VDP extracts two types of features: 1) coarse features derived from the statistics of binocular disparities and 2) fine features derived by estimating the neural activity associated with the processing of horizontal disparities. In particular, we deploy a model of horizontal disparity processing in the extrastriate middle temporal region of occipital lobe. We compare the performance of 3D-VDP with other recent discomfort prediction algorithms with respect to correlation against recorded subjective visual discomfort scores,and show that 3D-VDP is statistically superior to the other methods. PMID

  5. Improved Neural Signal Classification in a Rapid Serial Visual Presentation Task Using Active Learning.

    PubMed

    Marathe, Amar R; Lawhern, Vernon J; Wu, Dongrui; Slayback, David; Lance, Brent J

    2016-03-01

    The application space for brain-computer interface (BCI) technologies is rapidly expanding with improvements in technology. However, most real-time BCIs require extensive individualized calibration prior to use, and systems often have to be recalibrated to account for changes in the neural signals due to a variety of factors including changes in human state, the surrounding environment, and task conditions. Novel approaches to reduce calibration time or effort will dramatically improve the usability of BCI systems. Active Learning (AL) is an iterative semi-supervised learning technique for learning in situations in which data may be abundant, but labels for the data are difficult or expensive to obtain. In this paper, we apply AL to a simulated BCI system for target identification using data from a rapid serial visual presentation (RSVP) paradigm to minimize the amount of training samples needed to initially calibrate a neural classifier. Our results show AL can produce similar overall classification accuracy with significantly less labeled data (in some cases less than 20%) when compared to alternative calibration approaches. In fact, AL classification performance matches performance of 10-fold cross-validation (CV) in over 70% of subjects when training with less than 50% of the data. To our knowledge, this is the first work to demonstrate the use of AL for offline electroencephalography (EEG) calibration in a simulated BCI paradigm. While AL itself is not often amenable for use in real-time systems, this work opens the door to alternative AL-like systems that are more amenable for BCI applications and thus enables future efforts for developing highly adaptive BCI systems. PMID:26600162

  6. Neural activities in V1 create the bottom-up saliency map of natural scenes.

    PubMed

    Chen, Cheng; Zhang, Xilin; Wang, Yizhou; Zhou, Tiangang; Fang, Fang

    2016-06-01

    A saliency map is the bottom-up contribution to the deployment of exogenous attention. It, as well as its underlying neural mechanism, is hard to identify because of the influence of top-down signals. A recent study showed that neural activities in V1 could create a bottom-up saliency map (Zhang et al. in Neuron 73(1):183-192, 2012). In this paper, we tested whether their conclusion can generalize to complex natural scenes. In order to avoid top-down influences, each image was presented with a low contrast for only 50 ms and was followed by a high contrast mask, which rendered the whole image invisible to participants (confirmed by a forced-choice test). The Posner cueing paradigm was adopted to measure the spatial cueing effect (i.e., saliency) by an orientation discrimination task. A positive cueing effect was found, and the magnitude of the cueing effect was consistent with the saliency prediction of a computational saliency model. In a following fMRI experiment, we used the same masked natural scenes as stimuli and measured BOLD signals responding to the predicted salient region (relative to the background). We found that the BOLD signal in V1, but not in other cortical areas, could well predict the cueing effect. These results suggest that the bottom-up saliency map of natural scenes could be created in V1, providing further evidence for the V1 saliency theory (Li in Trends Cogn Sci 6(1):9-16, 2002). PMID:26879771

  7. What shall I be, what must I be: neural correlates of personal goal activation

    PubMed Central

    Strauman, Timothy J.; Detloff, Allison M.; Sestokas, Rima; Smith, David V.; Goetz, Elena L.; Rivera, Christine; Kwapil, Lori

    2013-01-01

    How is the brain engaged when people are thinking about their hopes, dreams, and obligations? Regulatory focus theory postulates two classes of personal goals and motivational systems for pursuing them. Ideal goals, such as hopes and aspirations, are pursued via the promotion system through “making good things happen.” Ought goals, such as obligations or responsibilities, are pursued via the prevention system through “keeping bad things from happening.” This study investigated the neural correlates of ideal and ought goal priming using an event-related fMRI design with rapid masked stimulus presentations. We exposed participants to their self-identified ideal and ought goals, yoked-control words and non-words. We also examined correlations between goal-related activation and measures of regulatory focus, behavioral activation/inhibition, and negative affect. Ideal priming led to activation in frontal and occipital regions as well as caudate and thalamus, whereas prevention goal priming was associated with activation in precuneus and posterior cingulate cortex. Individual differences in dysphoric/anxious affect and regulatory focus, but not differences in BAS/BIS strength, were predictive of differential activation in response to goal priming. The regions activated in response to ideal and ought goal priming broadly map onto the cortical midline network that has been shown to index processing of self-referential stimuli. Individual differences in regulatory focus and negative affect impact this network and appeared to influence the strength and accessibility of the promotion and prevention systems. The results support a fundamental distinction between promotion and prevention and extend our understanding of how personal goals influence behavior. PMID:23316145

  8. Detection of neural activity in the brains of Japanese honeybee workers during the formation of a "hot defensive bee ball".

    PubMed

    Ugajin, Atsushi; Kiya, Taketoshi; Kunieda, Takekazu; Ono, Masato; Yoshida, Tadaharu; Kubo, Takeo

    2012-01-01

    Anti-predator behaviors are essential to survival for most animals. The neural bases of such behaviors, however, remain largely unknown. Although honeybees commonly use their stingers to counterattack predators, the Japanese honeybee (Apis cerana japonica) uses a different strategy to fight against the giant hornet (Vespa mandarinia japonica). Instead of stinging the hornet, Japanese honeybees form a "hot defen