**Assistant Professor, Department of BiologyMember, ION**

Ph.D. Columbia University

B.Sc. Sharif University of Technology, Tehran, Iran

yashar@uoregon.edu

Lab Website**Office:** 238 Huestis **Phone: **541-346-7636

**Research Interests: **Theoretical neuroscience

**Overview: **Our lab's research is in theoretical neuroscience. Our broad interest is in understanding how large networks of neurons, e.g. those in the mammalian cerebral cortex, process sensory inputs and give rise to higher-level cognitive functions through their collective dynamics on multiple time scales. To shed light on the complexity of neurobiological phenomena we use mathematical models that capture a few core concepts or computational and dynamical principles. We also work on developing new statistical and computational tools for analyzing large, high-dimensional neurobiological and behavioral datasets. In pursuing these goals we use techniques from statistical physics, random matrix theory, machine learning and information theory. We collaborate with experimental labs here in the University of Oregon and elsewhere.

Current questions of interest include the following. How do randomness and nonnormality in the connectivity structure of networks affect their dynamics? What roles do the horizontal and feedback connections in sensory cortical areas play in contextual modulation (how e.g. the response of neurons in the visual cortex is affected by the visual context surrounding that stimulus) and ultimately in the dynamical representation of objects? Can the breakup of neural response types in the early auditory system be explained by efficient coding principles?

**RECENT PUBLICATIONS**

**Inferring neural circuit structure from datasets of heterogeneous tuning curves.**

PLoS Comput Biol. 2019 Apr 19;15(4):e1006816

Authors: Arakaki T, Barello G, Ahmadian Y

Abstract

Tuning curves characterizing the response selectivities of biological neurons can exhibit large degrees of irregularity and diversity across neurons. Theoretical network models that feature heterogeneous cell populations or partially random connectivity also give rise to diverse tuning curves. Empirical tuning curve distributions can thus be utilized to make model-based inferences about the statistics of single-cell parameters and network connectivity. However, a general framework for such an inference or fitting procedure is lacking. We address this problem by proposing to view mechanistic network models as implicit generative models whose parameters can be optimized to fit the distribution of experimentally measured tuning curves. A major obstacle for fitting such models is that their likelihood function is not explicitly available or is highly intractable. Recent advances in machine learning provide ways for fitting implicit generative models without the need to evaluate the likelihood and its gradient. Generative Adversarial Networks (GANs) provide one such framework which has been successful in traditional machine learning tasks. We apply this approach in two separate experiments, showing how GANs can be used to fit commonly used mechanistic circuit models in theoretical neuroscience to datasets of tuning curves. This fitting procedure avoids the computationally expensive step of inferring latent variables, such as the biophysical parameters of, or synaptic connections between, particular recorded cells. Instead, it directly learns generalizable model parameters characterizing the network's statistical structure such as the statistics of strength and spatial range of connections between different cell types. Another strength of this approach is that it fits the joint high-dimensional distribution of tuning curves, instead of matching a few summary statistics picked a priori by the user, resulting in a more accurate inference of circuit properties. More generally, this framework opens the door to direct model-based inference of circuit structure from data beyond single-cell tuning curves, such as simultaneous population recordings.

PMID: 31002660 [PubMed - as supplied by publisher]

**The Dynamical Regime of Sensory Cortex: Stable Dynamics around a Single Stimulus-Tuned Attractor Account for Patterns of Noise Variability.**

Neuron. 2018 May 16;98(4):846-860.e5

Authors: Hennequin G, Ahmadian Y, Rubin DB, Lengyel M, Miller KD

Abstract

Correlated variability in cortical activity is ubiquitously quenched following stimulus onset, in a stimulus-dependent manner. These modulations have been attributed to circuit dynamics involving either multiple stable states ("attractors") or chaotic activity. Here we show that a qualitatively different dynamical regime, involving fluctuations about a single, stimulus-driven attractor in a loosely balanced excitatory-inhibitory network (the stochastic "stabilized supralinear network"), best explains these modulations. Given the supralinear input/output functions of cortical neurons, increased stimulus drive strengthens effective network connectivity. This shifts the balance from interactions that amplify variability to suppressive inhibitory feedback, quenching correlated variability around more strongly driven steady states. Comparing to previously published and original data analyses, we show that this mechanism, unlike previous proposals, uniquely accounts for the spatial patterns and fast temporal dynamics of variability suppression. Specifying the cortical operating regime is key to understanding the computations underlying perception.

PMID: 29772203 [PubMed - in process]

**Properties of networks with partially structured and partially random connectivity.**

Phys Rev E Stat Nonlin Soft Matter Phys. 2015 Jan;91(1):012820

Authors: Ahmadian Y, Fumarola F, Miller KD

Abstract

Networks studied in many disciplines, including neuroscience and mathematical biology, have connectivity that may be stochastic about some underlying mean connectivity represented by a non-normal matrix. Furthermore, the stochasticity may not be independent and identically distributed (iid) across elements of the connectivity matrix. More generally, the problem of understanding the behavior of stochastic matrices with nontrivial mean structure and correlations arises in many settings. We address this by characterizing large random N×N matrices of the form A=M+LJR, where M,L, and R are arbitrary deterministic matrices and J is a random matrix of zero-mean iid elements. M can be non-normal, and L and R allow correlations that have separable dependence on row and column indices. We first provide a general formula for the eigenvalue density of A. For A non-normal, the eigenvalues do not suffice to specify the dynamics induced by A, so we also provide general formulas for the transient evolution of the magnitude of activity and frequency power spectrum in an N-dimensional linear dynamical system with a coupling matrix given by A. These quantities can also be thought of as characterizing the stability and the magnitude of the linear response of a nonlinear network to small perturbations about a fixed point. We derive these formulas and work them out analytically for some examples of M,L, and R motivated by neurobiological models. We also argue that the persistence as N→∞ of a finite number of randomly distributed outlying eigenvalues outside the support of the eigenvalue density of A, as previously observed, arises in regions of the complex plane Ω where there are nonzero singular values of L(-1)(z1-M)R(-1) (for z∈Ω) that vanish as N→∞. When such singular values do not exist and L and R are equal to the identity, there is a correspondence in the normalized Frobenius norm (but not in the operator norm) between the support of the spectrum of A for J of norm σ and the σ pseudospectrum of M.

PMID: 25679669 [PubMed - indexed for MEDLINE]

**Analysis of the stabilized supralinear network.**

Neural Comput. 2013 Aug;25(8):1994-2037

Authors: Ahmadian Y, Rubin DB, Miller KD

Abstract

We study a rate-model neural network composed of excitatory and inhibitory neurons in which neuronal input-output functions are power laws with a power greater than 1, as observed in primary visual cortex. This supralinear input-output function leads to supralinear summation of network responses to multiple inputs for weak inputs. We show that for stronger inputs, which would drive the excitatory subnetwork to instability, the network will dynamically stabilize provided feedback inhibition is sufficiently strong. For a wide range of network and stimulus parameters, this dynamic stabilization yields a transition from supralinear to sublinear summation of network responses to multiple inputs. We compare this to the dynamic stabilization in the balanced network, which yields only linear behavior. We more exhaustively analyze the two-dimensional case of one excitatory and one inhibitory population. We show that in this case, dynamic stabilization will occur whenever the determinant of the weight matrix is positive and the inhibitory time constant is sufficiently small, and analyze the conditions for supersaturation, or decrease of firing rates with increasing stimulus contrast (which represents increasing input firing rates). In work to be presented elsewhere, we have found that this transition from supralinear to sublinear summation can explain a wide variety of nonlinearities in cerebral cortical processing.

PMID: 23663149 [PubMed - indexed for MEDLINE]

**Modeling the impact of common noise inputs on the network activity of retinal ganglion cells.**

J Comput Neurosci. 2012 Aug;33(1):97-121

Authors: Vidne M, Ahmadian Y, Shlens J, Pillow JW, Kulkarni J, Litke AM, Chichilnisky EJ, Simoncelli E, Paninski L

Abstract

Synchronized spontaneous firing among retinal ganglion cells (RGCs), on timescales faster than visual responses, has been reported in many studies. Two candidate mechanisms of synchronized firing include direct coupling and shared noisy inputs. In neighboring parasol cells of primate retina, which exhibit rapid synchronized firing that has been studied extensively, recent experimental work indicates that direct electrical or synaptic coupling is weak, but shared synaptic input in the absence of modulated stimuli is strong. However, previous modeling efforts have not accounted for this aspect of firing in the parasol cell population. Here we develop a new model that incorporates the effects of common noise, and apply it to analyze the light responses and synchronized firing of a large, densely-sampled network of over 250 simultaneously recorded parasol cells. We use a generalized linear model in which the spike rate in each cell is determined by the linear combination of the spatio-temporally filtered visual input, the temporally filtered prior spikes of that cell, and unobserved sources representing common noise. The model accurately captures the statistical structure of the spike trains and the encoding of the visual stimulus, without the direct coupling assumption present in previous modeling work. Finally, we examined the problem of decoding the visual stimulus from the spike train given the estimated parameters. The common-noise model produces Bayesian decoding performance as accurate as that of a model with direct coupling, but with significantly more robustness to spike timing perturbations.

PMID: 22203465 [PubMed - indexed for MEDLINE]

**Learning unbelievable probabilities.**

Adv Neural Inf Process Syst. 2011 Dec;24:738-746

Authors: Pitkow X, Ahmadian Y, Miller KD

Abstract

Loopy belief propagation performs approximate inference on graphical models with loops. One might hope to compensate for the approximation by adjusting model parameters. Learning algorithms for this purpose have been explored previously, and the claim has been made that every set of locally consistent marginals can arise from belief propagation run on a graphical model. On the contrary, here we show that many probability distributions have marginals that cannot be reached by belief propagation using any set of model parameters or any learning algorithm. We call such marginals 'unbelievable.' This problem occurs whenever the Hessian of the Bethe free energy is not positive-definite at the target marginals. All learning algorithms for belief propagation necessarily fail in these cases, producing beliefs or sets of beliefs that may even be worse than the pre-learning approximation. We then show that averaging inaccurate beliefs, each obtained from belief propagation using model parameters perturbed about some learned mean values, can achieve the unbelievable marginals.

PMID: 28781497 [PubMed]

**Designing optimal stimuli to control neuronal spike timing.**

J Neurophysiol. 2011 Aug;106(2):1038-53

Authors: Ahmadian Y, Packer AM, Yuste R, Paninski L

Abstract

Recent advances in experimental stimulation methods have raised the following important computational question: how can we choose a stimulus that will drive a neuron to output a target spike train with optimal precision, given physiological constraints? Here we adopt an approach based on models that describe how a stimulating agent (such as an injected electrical current or a laser light interacting with caged neurotransmitters or photosensitive ion channels) affects the spiking activity of neurons. Based on these models, we solve the reverse problem of finding the best time-dependent modulation of the input, subject to hardware limitations as well as physiologically inspired safety measures, that causes the neuron to emit a spike train that with highest probability will be close to a target spike train. We adopt fast convex constrained optimization methods to solve this problem. Our methods can potentially be implemented in real time and may also be generalized to the case of many cells, suitable for neural prosthesis applications. With the use of biologically sensible parameters and constraints, our method finds stimulation patterns that generate very precise spike trains in simulated experiments. We also tested the intracellular current injection method on pyramidal cells in mouse cortical slices, quantifying the dependence of spiking reliability and timing precision on constraints imposed on the applied currents.

PMID: 21511704 [PubMed - indexed for MEDLINE]

**Incorporating naturalistic correlation structure improves spectrogram reconstruction from neuronal activity in the songbird auditory midbrain.**

J Neurosci. 2011 Mar 09;31(10):3828-42

Authors: Ramirez AD, Ahmadian Y, Schumacher J, Schneider D, Woolley SM, Paninski L

Abstract

Birdsong is comprised of rich spectral and temporal organization, which might be used for vocal perception. To quantify how this structure could be used, we have reconstructed birdsong spectrograms by combining the spike trains of zebra finch auditory midbrain neurons with information about the correlations present in song. We calculated maximum a posteriori estimates of song spectrograms using a generalized linear model of neuronal responses and a series of prior distributions, each carrying different amounts of statistical information about zebra finch song. We found that spike trains from a population of mesencephalicus lateral dorsalis (MLd) neurons combined with an uncorrelated Gaussian prior can estimate the amplitude envelope of song spectrograms. The same set of responses can be combined with Gaussian priors that have correlations matched to those found across multiple zebra finch songs to yield song spectrograms similar to those presented to the animal. The fidelity of spectrogram reconstructions from MLd responses relies more heavily on prior knowledge of spectral correlations than temporal correlations. However, the best reconstructions combine MLd responses with both spectral and temporal correlations.

PMID: 21389238 [PubMed - indexed for MEDLINE]