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D Chawla

Publications and source records attributed to D Chawla.

17 recordsLinked to original sources

Nonlinear PCA: characterizing interactions between modes of brain activity.

This paper presents a nonlinear principal component analysis (PCA) that identifies underlying sources causing the expression of spatial modes or patterns of activity in neuroimaging time-series. The critical aspect of this technique is that, in relation to conventional PCA, the sources can interact to produce (second-order) spatial modes that represent the modulation of one (first-order) spatial mode by another. This nonlinear PCA uses a simple neural network architecture that embodies a specific form for the nonlinear mixing of sources that cause observed data. This form is motivated by a second-order approximation to any general nonlinear mixing and emphasizes interactions among pairs of sources. By introducing these nonlinearities principal components obtain with a unique rotation and scaling that does not depend on the biologically implausible constraints adopted by conventional PCA. The technique is illustrated by application to functional (positron emission tomography and functional magnetic resonance imaging) imaging data where the ensuing first- and second-order modes can be interpreted in terms of distributed brain systems. The interactions among sources render the expression of any one mode context-sensitive, where that context is established by the expression of other modes. The examples considered include interactions between cognitive states and time (i.e. adaptation or plasticity in PET data) and among functionally specialized brain systems (using a fMRI study of colour and motion processing).

Acoustic Stimulation↗

Relating macroscopic measures of brain activity to fast, dynamic neuronal interactions.

In this article we used biologically plausible simulations of coupled neuronal populations to address the relationship between phasic and fast coherent neuronal interactions and macroscopic measures of activity that are integrated over time, such as the BOLD response in functional magnetic resonance imaging. Event-related, dynamic correlations were assessed using joint peristimulus time histograms and, in particular, the mutual information between stimulus-induced transients in two populations. This mutual information can be considered as an index of functional connectivity. Our simulations showed that functional connectivity or dynamic integration between two populations increases with mean background activity and stimulus-related rate modulation. Furthermore, as the background activity increases, the populations become increasingly sensitive to the intensity of the stimulus in terms of a predisposition to transient phase locking. This reflects an interaction between background activity and stimulus intensity in producing dynamic correlations, in that background activity augments stimulus-induced coherence modulation. This is interesting from a computational perspective because background activity establishes a context that may have a profound effect on event-related interactions or functional connectivity between neuronal populations. Finally, total firing rates, which subsume both background activity and stimulus-related rate modulation, were almost linearly related to the expression of dynamic correlations over large ranges of activities. These observations show that under the assumptions implicit in our model, rate-specific metrics based on rate or coherence modulation may be different perspectives on the same underlying dynamics. This suggests that activity (averaged over all peristimulus times), as measured in neuroimaging, may be tightly coupled to the expression of dynamic correlations.

Brain↗

The relationship between synchronization among neuronal populations and their mean activity levels.

In the past decade the importance of synchronized dynamics in the brain has emerged from both empirical and theoretical perspectives. Fast dynamic synchronous interactions of an oscillatory or nonoscillatory nature may constitute a form of temporal coding that underlies feature binding and perceptual synthesis. The relationship between synchronization among neuronal populations and the population firing rates addresses two important issues: the distinction between rate coding and synchronization coding models of neuronal interactions and the degree to which empirical measurements of population activity, such as those employed by neuroimaging, are sensitive to changes in synchronization. We examined the relationship between mean population activity and synchronization using biologically plausible simulations. In this article, we focus on continuous stationary dynamics. (In a companion article, Chawla (forthcoming), we address the same issue using stimulus-evoked transients.) By manipulation parameters such as extrinsic input, intrinsic noise, synaptic efficacy, density of extrinsic connections, the voltage-sensitive nature of postsynaptic mechanisms, the number of neurons, and the laminar structure within the populations, we were able to introduce variations in both mean activity and synchronization under a variety of simulated neuronal architectures. Analyses of the simulated spike trains and local field potentials showed that in nearly every domain of the model's parameter space, mean activity and synchronization were tightly coupled. This coupling appears to be mediated by an increase in synchronous gain when effective membrane time constants are lowered by increased activity. These observations show that under the assumptions implicit in our models, rate coding and synchrony coding in neural systems with reciprocal interconnections are two perspectives on the same underlying dynamic. This suggests that in the absence of specific mechanisms decoupling changes in synchronization from firing levels, indexes of brain activity that are based purely on synaptic activity (e.g., functional magnetic resonance imaging) may also be sensitive to changes in synchronous coupling.

Brain↗

Speed-dependent responses in V5: A replication study.

In a previous paper, we used fMRI to examine motion-sensitive responses in human area V5 as a function of stimulus speed. As predicted by electrophysiological findings, we observed optimal responses at intermediate speeds of around 7 to 30 degrees /s. These results revealed a nonlinear (inverted "U") dependency on speed that was also evident in V3a. In this paper we repeated the experiment using an improved stimulus and a larger range of speeds. We replicated our previous findings and extended our characterization of speed-dependent responses: Optimal responses were seen in V5 at speeds of 4 and 8 degrees /s and in V3a at speeds of 4 to 16 degrees /s. We were also able to show an interaction between speed (fast vs slow) and contrast (color > luminance) in V5. This interaction was anticipated on the basis of the different properties of the geniculate and extrageniculate inputs to V5. Finally, we were also able to demonstrate an interaction between motion (moving vs stationary) and contrast (color > luminance) in V4. This suggests that for V4, color-specific responses are augmented in the context of motion; or equivalently, that color contrast enhances any motion-sensitive responses in V4.

Artifacts↗

The physiological basis of attentional modulation in extrastriate visual areas.

Selective attention to color or motion enhances activity in specialized areas of extrastriate cortex, but mechanisms of attentional modulation remain unclear. By dissociating modulation of visually evoked transient activity from the baseline for a particular attentional set, human functional neuroimaging was used to investigate the physiological basis of such effects. Baseline activity in motion- and color-sensitive areas of extrastriate cortex was enhanced by selective attention to these attributes, even without moving or colored stimuli. Further, visually evoked responses increased along with baseline activity. These results are consistent with the hypothesis that attention modulates sensitivity of neuronal populations to inputs by changing background activity.

Attention↗

Revealing interactions among brain systems with nonlinear PCA.

In this work, we present a nonlinear principal component analysis (PCA) that identifies underlying sources causing the expression of spatial modes or patterns of activity in neuroimaging time series where these sources can interact to produce second-order modes. This nonlinear PCA uses a neural network architecture that embodies a specific form for the mixing of sources that is based on a second-order approximation to any general nonlinear mixing. The modes obtained have a unique rotation and scaling that does not depend on the biologically implausible constraints adopted by conventional PCA. Interactions among sources render the expression of any mode or brain system sensitive to the expression of others. The example considers interactions among functionally specialized brain systems (using a fMRI study of colour and motion processing).

Brain↗

Speed-dependent motion-sensitive responses in V5: an fMRI study.

This fMRI study examined motion-sensitive responses in human area V5 as a function of stimulus speed. Consistent with electrophysiological findings, we observed optimal responses at intermediate speeds of around 7 degrees/s to 30 degrees/s. The results are consistent with a nonlinear (inverted "U") dependency on speed that was also observed in V3a. V1 activation was observed to decrease linearly as speed increased. This is consistent with the fact that speed-sensitive cells in V1 have been shown to be tuned to much slower speeds than in V5.

Brain↗

Secretion of active human lecithin-cholesterol acyltransferase by insect cells infected with a recombinant baculovirus.

Difficulties in purifying the plasma enzyme lecithin-cholesterol acyltransferase (LCAT) have hampered detailed studies of its (patho)physiological role in lipoprotein metabolism and of structure-function relationships. Potentially, baculovirus-driven expression systems offer a powerful means to produce significant amounts of LCAT. Accordingly, full-length LCAT cDNA was cloned into pVL 1392, a high-level expression derivative of Autographa californica nuclear polyhedrosis virus (AcNPV), and the resultant plasmid was co-transfected into Trichoplusia ni insect cells (High 5 line) with a linearized viral DNA using lipofectin. Such viral DNA had a lethal mutation and grew only when recombined with a pVL1392-type rescue plasmid; cells infected with recombinant Autographa californica LCAT virus changed from a fibroblast-like morphology to rounded, but lacked the polyhedrin occlusion bodies characteristic of wild-type AcNPV infections. Enzymically active recombinant LCAT (rLCAT), sensitive to sulphydryl reagents, was secreted in the late phase of infection (36-48 h) but was absent with wild-type infections. The secreted protein had an apparent molecular mass of 53 kDa by SDS/PAGE, lower than that of native plasma LCAT; it was susceptible to endoglycosidase H digestion and was bound by concanavalin A, suggesting that precursor high-mannose N-glycan chains had not undergone full maturation to complex types. Pretreatment of the cells with tunicamycin to inhibit the first step of N-glycosylation led to intracellular accumulation of immature rLCAT (approximately 46-48 kDa) and a marked reduction in enzyme secreted. We conclude that the baculovirus gene-expression system will permit production of biologically active normal and mutant forms of LCAT protein.

Animals↗

Bowringia mildbraedii agglutinin: polypeptide composition, primary structure and homologies with other legume lectins.

The amino-acid sequences of the subunits of the lectin BMA from seeds of Bowringia mildbraedii have been determined. The data indicate that the lectin consists of a precursor polypeptide of approx. 29 kDa that is cleaved almost completely into two fragments of approx. 13.3 kDa (alpha subunit) and approx. 11.9 kDa (beta subunit), respectively. The beta subunit represents the N-terminal half of precursor polypeptides and is disulphide-linked in a beta beta dimer in the native (alpha beta)2 protein. BMA shows extensive amino-acid sequence homologies with known legume lectins. The site of post-translational proteolysis of the putative precursor occurs at a position similar to that identified in lectins obtained from other Sophoreae plants such as Sophora japonica and in Diocleae lectins such as Concanavalin A, but different from that of two chain lectins obtained from other tribes of the Papilionaceae.

Agglutinins↗

Interactions of Bowringia mildbraedii agglutinin with complex- and hybrid-type glycans.

Affinity chromatography on Bowringia mildbraedii agglutinin (BMA) Sepharose of glycopeptides confirmed a previous report using oligosaccharides (Animashaun, T. and Hughes, R. C. (1989) J. Biol. Chem. 264,4657-4663) that high affinity binding requires the sequence Man alpha 1---2 Man alpha 1----6 Man alpha 1----6 Man beta 1----4. However, moderate binding was still exhibited by structures lacking this sequence provided the oligosaccharide core sequence Man alpha 1----3[Man alpha 1----6]Man beta 1----4GlcNAc was present. This moderate binding was not affected by substitution with N-acetylglucosamine at C2 and C4, respectively, of the Man alpha 1----3 and Man beta 1----4 residues and BMA Sepharose should prove to be a useful tool for the isolation of bisected or non-bisected hybrid-type glycans.

Agglutinins↗

Effects of brefeldin A on oligosaccharide processing. Evidence for decreased branching of complex-type glycans and increased formation of hybrid-type glycans.

Brefeldin A (BFA), a drug that induces redistribution of Golgi-apparatus proteins into the endoplasmic reticulum, was used to determine the role of subcellular compartmentalization in the processing of asparagine-linked oligosaccharides. Baby-hamster kidney cells were pulse-labelled with [3H]mannose for 30-60 min and chased for up to several hours in the presence or in the absence of BFA or labelled continuously for several hours with and without the drug. Cellular glycoproteins were digested to glycopeptides with Pronase and either fractionated into glycan classes by lectin affinity chromatography or digested further by endoglycosidase H and endoglycosidase D. Released oligosaccharides obtained in the latter procedure were then separated from each other and from endoglycosidase-resistant glycopeptides by paper chromatography. The results show that BFA induces a very fast processing of protein-linked Glc3Man9GlcNAc2 oligosaccharide down to man5GlcNAc2 and conversion into complex-type and hybrid-type glycans. The major difference between untreated and BFA-treated cells is a large increase in bi-antennary and hybrid-type glycans in the latter cells. These results indicate that galactosylation of a mono-antennary GlcNAcMan5GlcNAc2 hybrid blocks subsequent action by mannosidase II and N-acetylglucosaminyl transferase II, producing galactosylated hybrid-type glycans. Similarly, galactosylation of the product of N-acetylglucosaminyltransferases I and II, i.e. a Man3GlcNAc2 core substituted with GlcNAc beta 1----2 on both alpha 1----3- and alpha 1----6-linked mannose residues, blocks branching N-acetylglucosaminyltransferases IV and V, thereby causing an increase in bi-antennary glycans and a decrease in tri- and tetra-antennary glycans.

Animals↗

Optimum needle length for DPT inoculation of Indian infants.

Correct placement of the injected DPT vaccine into the deep muscular layers decreases the local reactions, including the sterile abscess formation. However, recommendations on size of the needle to be used and the angle of injection are not easily available, are not uniform and are based on case reports. The only study based on scientific data of ultrasonographic measurement of fat layer and muscle layer thickness of thigh of only 24 infants of 4 months age covers only American children. (Hick et al, Pediatrics 1989; 84: 136-37). In the present study, we have produced similar data on 215 Indian children belonging to all those age groups in which DPT vaccinations are given. Mean thickness of skin + fat layer in the middle one-third of the anterolateral aspect of thigh was 1.03 +/- 0.23 cm, 1.04 +/- 0.21 cm, 0.95 +/- 0.19 cm and 1.06 +/- 0.27 cm in the age groups of 6-12 weeks (Groups I), 13-18 weeks (Group II), 19-24 weeks (Groups III) and 18 +/- 1 month (Group IV) respectively. These age groups correspond to the timings of first 3 primary doses and the first booster dose of the DPT vaccine in our immunization clinic. Mean thickness of all the soft tissues together at the same site were 1.87 +/- 0.35, 2.17 +/- 0.38, 2.07 +/- 0.39 and 2.07 +/- 0.26 cm respectively for the groups I to IV.(ABSTRACT TRUNCATED AT 250 WORDS)

Developing Countries↗

CT appearances in macronodular hepatosplenic tuberculosis: a review with five additional new cases.

Pseudotumoral or macronodular hepatosplenic tuberculosis (HSTB) is rare. Only 31 cases have been documented in imaging literature so far. Presented is the clinico-imaging review with five additional new cases of this uncommon variety. Due to nonspecific wide spectrum of imaging appearances, biopsy is mandatory in almost all cases. Clinical recovery and resolution of lesions on imaging may not be directly proportional.

Abdominal Pain↗

Zero-lag synchronous dynamics in triplets of interconnected cortical areas.

Oscillatory and synchronized activities involving widespread populations of neurons in neocortex are associated with the execution of complex sensorimotor tasks and have been proposed to participate in the 'binding' of sensory attributes during perceptual synthesis. How the brain constructs these coherent firing patterns remains largely unknown. Several mechanisms of intracortical synchronization have been considered, in particular mutual inhibition and reciprocal excitation. These mechanisms fail to account for the zero-lag correlations observed among areas located at different levels in the visual hierarchy because the asymmetric laminar organization of ascending and descending connections in this hierarchy would predict systematic inter-areal phase lags. Here we show through detailed computer simulations that, when triplets rather than pairs of reciprocally connected areas in a cortical hierarchy are considered, zero-lag synchronization emerges naturally from their three-way interactions. These simulations were motivated by the observation that most areas in the cat and macaque monkey visual cortex are organized in such triplets. Our results suggest that patterns of anatomical connections in the mammalian neocortex provide a structural basis for the multi-level synchronization of neuronal activity.

Action Potentials↗