Biomedical subjects

Aaditya V Rangan

Publications and source records attributed to Aaditya V Rangan.

5 recordsLinked to original sources

PubMed2026

Genomic dimensions deconstruct the clinical heterogeneity of bipolar disorder.

Bipolar disorder's (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder-and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic-GABAergic gradient along the psychotic factor. BD's genetic architecture appears hierarchical-a general liability resolving into dimensions of course and comorbidity, beyond subtypes.

Journal Article↗

PubMed2006

Fast numerical methods for simulating large-scale integrate-and-fire neuronal networks.

We discuss numerical methods for simulating large-scale, integrate-and-fire (I&F) neuronal networks. Important elements in our numerical methods are (i) a neurophysiologically inspired integrating factor which casts the solution as a numerically tractable integral equation, and allows us to obtain stable and accurate individual neuronal trajectories (i.e., voltage and conductance time-courses) even when the I&F neuronal equations are stiff, such as in strongly fluctuating, high-conductance states; (ii) an iterated process of spike-spike corrections within groups of strongly coupled neurons to account for spike-spike interactions within a single large numerical time-step; and (iii) a clustering procedure of firing events in the network to take advantage of localized architectures, such as spatial scales of strong local interactions, which are often present in large-scale computational models-for example, those of the primary visual cortex. (We note that the spike-spike corrections in our methods are more involved than the correction of single neuron spike-time via a polynomial interpolation as in the modified Runge-Kutta methods commonly used in simulations of I&F neuronal networks.) Our methods can evolve networks with relatively strong local interactions in an asymptotically optimal way such that each neuron fires approximately once in [Formula: see text] operations, where N is the number of neurons in the system. We note that quantifications used in computational modeling are often statistical, since measurements in a real experiment to characterize physiological systems are typically statistical, such as firing rate, interspike interval distributions, and spike-triggered voltage distributions. We emphasize that it takes much less computational effort to resolve statistical properties of certain I&F neuronal networks than to fully resolve trajectories of each and every neuron within the system. For networks operating in realistic dynamical regimes, such as strongly fluctuating, high-conductance states, our methods are designed to achieve statistical accuracy when very large time-steps are used. Moreover, our methods can also achieve trajectory-wise accuracy when small time-steps are used.

Algorithms↗

PubMed2006

Maximum-entropy closures for kinetic theories of neuronal network dynamics.

We analyze (1 + 1)D kinetic equations for neuronal network dynamics, which are derived via an intuitive closure from a Boltzmann-like equation governing the evolution of a one-particle (i.e., one-neuron) probability density function. We demonstrate that this intuitive closure is a generalization of moment closures based on the maximum-entropy principle. By invoking maximum-entropy closures, we show how to systematically extend this kinetic theory to obtain higher-order, kinetic equations and to include coupled networks of both excitatory and inhibitory neurons.

Algorithms↗

PubMed2005

Modeling the spatiotemporal cortical activity associated with the line-motion illusion in primary visual cortex.

Our large-scale computational model of the primary visual cortex that incorporates orientation-specific, long-range couplings with slow NMDA conductances operates in a fluctuating dynamic state of intermittent desuppression (IDS), which captures the behavior of coherent spontaneous cortical activity, as revealed by in vivo optical imaging based on voltage-sensitive dyes. Here, we address the functional significance of the IDS cortical operating points by investigating our model cortex response to the Hikosaka line-motion illusion (LMI) stimulus-a cue of a quickly flashed stationary square followed a few milliseconds later by a stationary bar. As revealed by voltage-sensitive dye imaging, there is an intriguing similarity between the cortical spatiotemporal activity in response to (i) the Hikosaka LMI stimulus and (ii) a small moving square. This similarity is believed to be associated with the preattentive illusory motion perception. Our numerical cortex produces similar spatiotemporal patterns in response to the two stimuli above, which are both in very good agreement with experimental results. The essential network mechanisms underpinning the LMI phenomenon in our model are (i) the spatiotemporal structure of the LMI input as sculpted by the lateral geniculate nucleus, (ii) a priming effect of the long-range NMDA-type cortical coupling, and (iii) the NMDA conductance-voltage correlation manifested in the IDS state. This mechanism in our model cortex, in turn, suggests a physiological underpinning for the LMI-associated patterns in the visual cortex of anaesthetized cat.

Animals↗

PubMed2005

Architectural and synaptic mechanisms underlying coherent spontaneous activity in V1.

To investigate the existence and the characteristics of possible cortical operating points of the primary visual cortex, as manifested by the coherent spontaneous ongoing activity revealed by real-time optical imaging based on voltage-sensitive dyes, we studied numerically a very large-scale ( approximately 5 x 10(5)) conductance-based, integrate-and-fire neuronal network model of an approximately 16-mm(2) patch of 64 orientation hypercolumns, which incorporates both isotropic local couplings and lateral orientation-specific long-range connections with a slow NMDA component. A dynamic scenario of an intermittent desuppressed state (IDS) is identified in the computational model, which is a dynamic state of (i) high conductance, (ii) strong inhibition, and (iii) large fluctuations that arise from intermittent spiking events that are strongly correlated in time as well as in orientation domains, with the correlation time of the fluctuations controlled by the NMDA decay time scale. Our simulation results demonstrate that the IDS state captures numerically many aspects of experimental observation related to spontaneous ongoing activity, and the specific network mechanism of the IDS may suggest cortical mechanisms and the cortical operating point underlying observed spontaneous activity.

Animals↗