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Ramesh Srinivasan

Publications and source records attributed to Ramesh Srinivasan.

16 recordsLinked to original sources

Functional connectivity of frontal cortex in healthy and ADHD children reflected in EEG coherence.

Abnormal functional brain connectivity is a candidate factor in developmental brain disorders associated with cognitive dysfunction. We analyzed a substantial (10 min per subject) record of dense array electroencephalography with spectral power and coherence methods in attention-deficit hyperactivity disorder (ADHD) (n = 42) and control (n = 21) 10- to 13-year-old children. We found topographically distinct narrow band coherence differences between subject groups: ADHD subjects showed elevated coherence in the lower alpha (8 Hz) band and reduced coherence in the upper alpha (10-11 Hz) band. The 8-Hz ADHD elevation and a 2- to 6-Hz control group coherence elevation were independent of stimulus presentation. In response to visual stimulation, the ADHD group exhibited reduced evoked potential power and elevated frontal coherence. Only the upper alpha band control group coherence elevation discriminated according to ADHD group medication status. The findings suggest a static state of deficient connectivity in ADHD and a stimulus-induced state of overconnectivity within and between frontal hemispheres.

Adolescent↗

A theoretical basis for standing and traveling brain waves measured with human EEG with implications for an integrated consciousness.

OBJECTIVE: We propose a theoretical framework for EEG and evoked potential studies based on the single postulate that these data are composed of a combination of waves (as this term is used in the physical sciences) and thalamocortical network activity. METHODS: Using known properties of traveling and standing waves, independent of any neocortical dynamic theory, our simple postulate leads to experimental predictions, several of which have now been verified. A mathematical-physiological theory of "brain waves" based on known (but highly idealized) properties of cortical synaptic action and corticocortical fibers is used to support the framework. RESULTS: Brain waves are predicted with links between temporal frequencies and the spatial distributions of synaptic activity. Such dispersion relations, which essentially define more general phenomena as waves, are shown to restrict the spatial-temporal dynamics of synaptic action with many experimental EEG consequences. CONCLUSIONS: The proposed framework accounts for several salient features of spontaneous EEG and evoked potentials. SIGNIFICANCE: We conjecture that wave-like behavior of synaptic action may facilitate interactions between remote cell assemblies, providing an important mechanism for the functional integration underlying conscious experience.

Algorithms↗

Steady-state visual evoked potentials: distributed local sources and wave-like dynamics are sensitive to flicker frequency.

Steady-state visual evoked potentials (SSVEPs) are used in cognitive and clinical studies of brain function because of excellent signal-to-noise ratios and relative immunity to artifacts. SSVEPs also provide a means to characterize preferred frequencies of neocortical dynamic processes. In this study, SSVEPs were recorded with 110 electrodes while subjects viewed random dot patterns flickered between 3 and 30 Hz. Peaks in SSVEP power were observed at delta (3 Hz), lower alpha (7 and 8 Hz), and upper alpha band (12 and 13 Hz) frequencies; the spatial distribution of SSVEP power is also strongly dependent on the input frequency suggesting cortical resonances. We characterized the cortical sources that generate SSVEPs at different input frequencies by applying surface Laplacians and spatial spectral analysis. Laplacian SSVEPs recorded are sensitive to small changes (1-2 Hz) in the input frequency at occipital and parietal electrodes indicating distinct local sources. At 10 Hz, local source activity occurs in multiple cortical regions; Laplacian SSVEPs are also observed in lateral frontal electrodes. Laplacian SSVEPs are negligible at many frontal electrodes that elicit strong potential SSVEPs at delta, lower alpha, and upper alpha bands. One-dimensional (anterior-posterior) spatial spectra indicate that distinct large-scale source distributions contribute SSVEP power in these frequency bands. In the upper alpha band, spatial spectra indicate the presence of long-wavelength (> 15 cm) traveling waves propagating from occipital to prefrontal electrodes. In the delta and lower alpha band, spatial spectra indicate that long-wavelength source distributions over posterior and anterior regions form standing-wave patterns. These results suggest that the SSVEP is generated by both (relatively stationary) localized sources and distributed sources that exhibit characteristics of wave phenomena.

Adult↗

Source analysis of EEG oscillations using high-resolution EEG and MEG.

We investigated spatial properties of the source distributions that generate scalp electroencephalographic (EEG) oscillations. The inherent complexity of the spatio-temporal dynamics of EEG oscillations indicates that conceptual models that view source activity as consisting only of a few "equivalent dipoles" are inadequate. We present an approach that uses volume conduction models to characterize the distinct spatial filtering of cortical source activity by average reference EEG, high-resolution EEG, and magnetoencephalography (MEG). By comparing these three measures, we can make inferences about the sources of EEG oscillations without having to make prior assumptions about the sources. We apply this approach to spontaneous EEG oscillations observed with eyes closed at rest. Both EEG and MEG recordings show robust alpha rhythms over posterior regions of the cortex; however, the dominant frequency of these rhythms varies between EEG and MEG recordings. Frontal alpha and theta rhythms are generated almost exclusively by superficial radial dipole layers that generate robust EEG signals but very little MEG signals; these sources are presumably mainly in the gyral crowns of frontal cortex. MEG and high-resolution EEG estimates of alpha rhythms provide evidence of local tangential and radial sources in the posterior cortex, lying mainly on sulcal and gyral surfaces. Despite the detailed information about local radial and tangential sources potentially afforded by high-resolution EEG and MEG, it is also evident that the alpha and theta rhythms receive contributions from non-local source activity, for instance large dipole layers distributed over lobeal or (potentially) even larger spatial scales.

Animals↗

Clinical safety of Lactobacillus casei shirota as a probiotic in critically ill children.

OBJECTIVE: Diarrhea is frequently observed among critically ill children (CIC) admitted for intensive care. There is increasing evidence that probiotics decrease the incidence of acute infectious and nosocomial and antibiotic induced diarrhea amongst children hospitalized in nonintensive care settings. Despite theoretic advantages for the use of probiotics in CIC, safety has remained a concern in this vulnerable group. The objective of this study was to establish clinical safety (invasive infection/colonization) of Lactobacillus casei shirota (LCS) used as a probiotic in CIC. METHODS: Prospective, descriptive pilot study on children admitted to a pediatric intensive care unit. Data regarding safety were collected on the initial recruits to a randomized controlled trial aimed to study the effects of LCS on stool frequency and consistency in CIC. Safety was assessed by bacteriologic surveillance for LCS in surface swabs and endotracheal aspirates (colonization) as well as blood, urine, and sterile body fluid cultures (invasive infection/bacteremia). RESULTS: Safety data were available on 28 patients. LCS was cultured from the feces of five of the six study subjects who opened bowels during their stay on the pediatric intensive care unit. There was no evidence of either colonization or bacteremia with LCS in bacteriologic cultures obtained from study subjects. The preparation was well tolerated with no apparent side effects. CONCLUSIONS: Our pilot safety study suggests that the use of LCS as a probiotic in enterally fed CIC is safe.

Adolescent↗

Anatomical constraints on source models for high-resolution EEG and MEG derived from MRI.

Electroencephalography (EEG) remains the primary tool for measuring changes in dynamic brain function due to disease state with the millisecond temporal resolution of neuronal activity. In recent decades EEG has been supplanted by CT and MRI for the localization of tumors and lesions in the brain. In contrast to the excellent temporal resolution of EEG, the spatial information in EEG is limited by the volume conduction of currents through the tissues of the head. We have extracted source models (position and orientation) from MRI scans to investigate the theoretical relationship between brain sources and EEG recorded on the scalp. Although detailed information about the boundaries between different tissues can also be obtained from MRI, these models are only approximate because of our relatively poor knowledge of the conductivities of the different tissue compartments in living heads. We also compare the resolution of EEG with magnetoecephalography (MEG), which offers the advantage of requiring less detail about volume conduction in the head. The brain's magnetic field depends only on the position of sources in the brain and the position and orientation of the sensors. We demonstrate that EEG and MEG space average neural activity over comparably large volumes of the brain; however, they are preferentially sensitive to sources of different orientation suggesting a complementary role for EEG and MEG. High-resolution EEG methods potentially yield much better localization of source activity in superficial brain areas. These methods do not make any assumptions about the sources, and can be easily co-registered with the brain surface derived from MRI. While there is much information to be gained by using anatomical MRI to develop models of the generators of EEG/MEG, functional neuroimaging (e.g., fMRI) signals and EEG/MEG signals are not easily related.

Algorithms↗

Attentional modulation of SSVEP power depends on the network tagged by the flicker frequency.

Modulation of the steady-state visual evoked potential (SSVEP) by attention was studied in detail using 15 'tag' frequencies in the range of 2.5-20 Hz. The stimuli were two series of random disc search arrays superimposed on two concentric color-marked annuli respectively. Two series of arrays were updated independently; one updated at one fixed frequency (flicker) and the other updated randomly according to a white noise distribution (random broadband flicker, rbbf). On each trial, the observer was instructed to attend one annulus and to detect a target (a triangle) that occasionally appeared in a random disc array in the attended annulus. The SSVEP results show that the choice of flicker frequency selects which cortical network synchronizes to the flicker two distinct cortical networks showed different effects of attention. SSVEP power and the effects of attention on SSVEP power strongly depend on both flicker frequency and radial position of rbbf annulus. At flicker frequencies in the delta band (2-4 Hz), and in the upper alpha band (10-11 Hz), an occipital-frontal network appears to phase-lock to the flicker when attending to the flicker, increasing the magnitude of the SSVEP. At flicker frequencies in the lower alpha band (8-10 Hz), a global response to a peripheral flickering stimulus, that includes parietal cortex and posterior frontal cortex, has higher amplitude when attention is directed away from the flickering peripheral stimulus and towards a competing rbbf stimulus in the fovea. Increases in SSVEP power when attention is directed to peripheral flicker are always associated with increases in phase locking. By contrast, at frequencies in the lower alpha band, increases in SSVEP power when attention is directed away from the flicker and towards foveal stimuli are not associated with changes in phase-locking. Thus, whether attention to a flicker stimulus increases or decreases SSVEP amplitude and phase locking depends on which of two cortical networks, which have distinct spatial and dynamic properties, is selected by the flicker frequency.

Action Potentials↗

MEG phase follows conscious perception during binocular rivalry induced by visual stream segregation.

We have investigated an unusual form of binocular rivalry between two images that are flickered one to each eye, but are never presented simultaneously to the observer. The images were presented in alternation, with a brief dark period between the images. When the flicker frequency was < 5 Hz, the subjects primarily experienced a unitary flicker that alternated between the two images. When the flicker frequency was > 5 Hz, the subjects primarily experienced two single-image flickers that rival. We investigated magnetoencephalography (MEG) responses at the flicker frequency of the rival stimuli. We found that at some recording locations responses are phase-locked to the flicker that is consciously being perceived. At each flicker rate that induced rivalry, phase shifts following the conscious percept were found consistently at MEG sensors over midline frontal lobe. Most of these sensors show higher magnitude responses when two rivaling flickers are perceived than when a unitary alternating color flicker is perceived. At sensors over occipital lobe, the sensor locations that phase-locked to the perceived flicker depended on the color, orientation, and frequency of flicker. By contrast, sensors over parietal cortex respond preferentially to one flicker, even as the conscious percept changes. Apparently, a large-scale network of cell assemblies in occipital and frontal cortex, responds preferentially to the perceived stimulus during rivalry, and is sensitive to the timing of the flicker driving the conscious percept.

Adult↗

Four-dimensional ultrafast electron microscopy.

Electron microscopy is arguably the most powerful tool for spatial imaging of structures. As such, 2D and 3D microscopies provide static structures with subnanometer and increasingly with angstrom-scale spatial resolution. Here we report the development of 4D ultrafast electron microscopy, whose capability imparts another dimension to imaging in general and to dynamics in particular. We demonstrate its versatility by recording images and diffraction patterns of crystalline and amorphous materials and images of biological cells. The electron packets, which were generated with femtosecond laser pulses, have a de Broglie wavelength of 0.0335 angstroms at 120 keV and have as low as one electron per pulse. With such few particles, doses of few electrons per square ångstrom, and ultrafast temporal duration, the long sought after but hitherto unrealized quest for ultrafast electron microscopy has been realized. Ultrafast electron microscopy should have an impact on all areas of microscopy, including biological imaging.

Animals↗

Dark structures in molecular radiationless transitions determined by ultrafast diffraction.

The intermediate structures formed through radiationless transitions are termed "dark" because their existence is inferred indirectly from radiative transitions. We used ultrafast electron diffraction to directly determine these transient structures on both ground-state and excited-state potential energy surfaces of several aromatic molecules. The resolution in space and time (0.01 angstrom and 1 picosecond) enables differentiation between competing nonradiative pathways of bond breaking, vibronic coupling, and spin transition. For the systems reported here, the results reveal unexpected dynamical behavior. The observed ring opening of the structure depends on molecular substituents. This, together with the parallel bifurcation into physical and chemical channels, redefines structural dynamics of the energy landscape in radiationless processes.

Journal Article↗

Pamidronate lines.

Explore the source record for details and available documents.

Antineoplastic Agents↗

Direct determination of hydrogen-bonded structures in resonant and tautomeric reactions using ultrafast electron diffraction.

We elucidate the keto-enol tautomeric equilibrium in acetylacetone, the structure of both keto and enol forms, and the nature of the intramolecular O-H...O HB in enolic acetylacetone using our ultrafast electron diffraction apparatus, thereby shedding new light on the nature of the hydrogen bond in resonant tautomeric structures. The enolic structure exhibits some pi-resonance delocalization; however, this delocalization is not strong enough to give a symmetric skeletal geometry. The long O...O distance in the refined structure renders the homonuclear O-H...O hydrogen bond in acetylacetone localized and asymmetric.

Journal Article↗

Steatohepatitis and unsuspected micronodular cirrhosis in Dorfman-Chanarin syndrome with documented ABHD5 mutation.

Mutation in ABHD5 causes Dorfman-Chanarin syndrome (DCS), a multisystem triglyceride storage disorder. Ultrastructural study of leukocytes confirmed DCS in a child homozygous for a novel ABHD5 mutation, with ichthyosis, developmental delay, and steatohepatitis with cirrhosis, manifest only as elevated aminotranferase levels. We recommend early assessment for liver disease in DCS.

1-Acylglycerol-3-Phosphate O-Acyltransferase↗

Profile of GERD in the adult population of a northeast urban community.

STUDY: An observational, cross-sectional, epidemiology study of the characteristics of GERD in a large northeast urban population was performed using a self-responding 84-question survey. Four-hundred and ten surveys were completed from a population sample with demographics comparable to those of the 1990 US Census data. RESULTS: No differences in heartburn frequency (monthly) were found between white or black, male or female respondents. Heartburn was significantly (P = 0.01) less common in those over age 60 (36.9%) than in young (47.7%) or middle-age (57.3%) respondents. Impact of heartburn on social activities was less (P = 0.002) in the over 60 group (4.9%) compared with the young (19.3%) or middle-age (20.0%) groups. Although 49.8% of respondents were familiar to the term GERD, few were aware that swallowing difficulty (17.3%), asthma (9.3%) or hoarseness (11.5%) were possible symptoms and similar numbers considered stroke (33.2%) and cancer (31.7%) to be complications of GERD. CONCLUSIONS: Frequency of GERD symptoms in the United States is unaffected by gender or race but is lower in the elderly.

Adult↗

Implications of recording strategy for estimates of neocortical dynamics with electroencephalography.

Neocortical dynamics evidently involves very complex, nonlinear processes including top-down and bottom-up interactions across spatial scales. The dynamics may also be strongly influenced by global (periodic) boundary conditions. The primary experimental measure of human neocortical dynamics at short time scales ( approximately few ms) is the scalp electroencephalogram (EEG). It is shown that different recording and data analysis strategies are sensitive to different parts of the spatial spectrum. Thus experimental measures of system dynamics (e.g., correlation dimension estimates) can generally be expected to depend on experimental method. These ideas are illustrated in two ways: a large scale, quasilinear theory of neocortical dynamics in which standing wave phenomenon occur with predicted frequencies in the general range of EEG, and a relatively simple nonlinear physical system consisting of a linear string with attached nonlinear springs. The string/springs system is integrated numerically to illustrate transitions from periodic to chaotic behavior as mesoscopic nonlinear influences dominate macroscopic linear effects. The implications of these results for new theories of neocortical dynamics, experimental estimates of dynamic properties, and cognitive EEG studies are considered.

Journal Article↗