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Pachitariu Lab / Publications
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30 Publications

Showing 21-30 of 30 results
06/27/17 | Robustness of spike deconvolution for calcium imaging of neural spiking.
Pachitariu M, Stringer C, Harris KD
bioRxiv. 2017 Jun 27:156786. doi: https://doi.org/10.1101/156786

Calcium imaging is a powerful method to record the activity of neural populations, but inferring spike times from calcium signals is a challenging problem. We compared multiple approaches using multiple datasets with ground truth electrophysiology, and found that simple non-negative deconvolution (NND) outperformed all other algorithms. We introduce a novel benchmark applicable to recordings without electrophysiological ground truth, based on the correlation of responses to two stimulus repeats, and used this to show that unconstrained NND also outperformed the other algorithms when run on 'zoomed out' datasets of ~10,000 cell recordings. Finally, we show that NND-based methods match the performance of a supervised method based on convolutional neural networks, while avoiding some of the biases of such methods, and at much faster running times. We therefore recommend that spikes be inferred from calcium traces using simple NND, due to its simplicity, efficiency and accuracy.

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01/09/17 | Visual motion computation in recurrent neural networks.
Pachitariu M, Sahani M
bioRxiv. 2017 Jan 09:099101. doi: https://doi.org/10.1101/099101

Populations of neurons in primary visual cortex (V1) transform direct thalamic inputs into a cortical representation which acquires new spatio-temporal properties. One of these properties, motion selectivity, has not been strongly tied to putative neural mechanisms, and its origins remain poorly understood. Here we propose that motion selectivity is acquired through the recurrent mechanisms of a network of strongly connected neurons. We first show that a bank of V1 spatiotemporal receptive fields can be generated accurately by a network which receives only instantaneous inputs from the retina. The temporal structure of the receptive fields is generated by the long timescale dynamics associated with the high magnitude eigenvalues of the recurrent connectivity matrix. When these eigenvalues have complex parts, they generate receptive fields that are inseparable in time and space, such as those tuned to motion direction. We also show that the recurrent connectivity patterns can be learnt directly from the statistics of natural movies using a temporally-asymmetric Hebbian learning rule. Probed with drifting grating stimuli and moving bars, neurons in the model show patterns of responses analogous to those of direction-selective simple cells in primary visual cortex. These computations are enabled by a specific pattern of recurrent connections, that can be tested by combining connectome reconstructions with functional recordings.

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12/07/16 | Inhibitory control of correlated intrinsic variability in cortical networks.
Stringer C, Pachitariu M, Steinmetz NA, Okun M, Bartho P, Harris KD, Sahani M, Lesica NA
eLife. 2016 Dec 07;5:. doi: 10.7554/eLife.19695

Cortical networks exhibit intrinsic dynamics that drive coordinated, large-scale fluctuations across neuronal populations and create noise correlations that impact sensory coding. To investigate the network-level mechanisms that underlie these dynamics, we developed novel computational techniques to fit a deterministic spiking network model directly to multi-neuron recordings from different rodent species, sensory modalities, and behavioral states. The model generated correlated variability without external noise and accurately reproduced the diverse activity patterns in our recordings. Analysis of the model parameters suggested that differences in noise correlations across recordings were due primarily to differences in the strength of feedback inhibition. Further analysis of our recordings confirmed that putative inhibitory neurons were indeed more active during desynchronized cortical states with weak noise correlations. Our results demonstrate that network models with intrinsically-generated variability can accurately reproduce the activity patterns observed in multi-neuron recordings and suggest that inhibition modulates the interactions between intrinsic dynamics and sensory inputs to control the strength of noise correlations.

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12/05/16 | Fast and accurate spike sorting of high-channel count probes with KiloSort.
Pachitariu M, Steinmetz NA, Kadir SN, Carandini M, Harris KD
Neural Information Processing Systems (NIPS 2016). 2016 Dec 05:

New silicon technology is enabling large-scale electrophysiological recordings in vivo from hundreds to thousands of channels. Interpreting these recordings requires scalable and accurate automated methods for spike sorting, which should minimize the time required for manual curation of the results. Here we introduce KiloSort, a new integrated spike sorting framework that uses template matching both during spike detection and during spike clustering. KiloSort models the electrical voltage as a sum of template waveforms triggered on the spike times, which allows overlapping spikes to be identified and resolved. Unlike previous algorithms that compress the data with PCA, KiloSort operates on the raw data which allows it to construct a more accurate model of the waveforms. Processing times are faster than in previous algorithms thanks to batch-based optimization on GPUs. We compare KiloSort to an established algorithm and show favorable performance, at much reduced processing times. A novel post-clustering merging step based on the continuity of the templates further reduced substantially the number of manual operations required on this data, for the neurons with near-zero error rates, paving the way for fully automated spike sorting of multichannel electrode recordings.

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06/17/15 | Learning enhances sensory and multiple non-sensory representations in primary visual cortex.
Poort J, Khan AG, Pachitariu M, Nemri A, Orsolic I, Krupic J, Bauza M, Sahani M, Keller GB, Mrsic-Flogel TD, Hofer SB
Neuron. 2015 Jun 17;86(6):1478-90. doi: 10.1016/j.neuron.2015.05.037

We determined how learning modifies neural representations in primary visual cortex (V1) during acquisition of a visually guided behavioral task. We imaged the activity of the same layer 2/3 neuronal populations as mice learned to discriminate two visual patterns while running through a virtual corridor, where one pattern was rewarded. Improvements in behavioral performance were closely associated with increasingly distinguishable population-level representations of task-relevant stimuli, as a result of stabilization of existing and recruitment of new neurons selective for these stimuli. These effects correlated with the appearance of multiple task-dependent signals during learning: those that increased neuronal selectivity across the population when expert animals engaged in the task, and those reflecting anticipation or behavioral choices specifically in neuronal subsets preferring the rewarded stimulus. Therefore, learning engages diverse mechanisms that modify sensory and non-sensory representations in V1 to adjust its processing to task requirements and the behavioral relevance of visual stimuli.

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02/04/15 | State-dependent population coding in primary auditory cortex.
Pachitariu M, Lyamzin DR, Sahani M, Lesica NA
The Journal of Neuroscience : the official journal of the Society for Neuroscience. 2015 Feb 04;35(5):2058-73. doi: 10.1523/JNEUROSCI.3318-14.2015

Sensory function is mediated by interactions between external stimuli and intrinsic cortical dynamics that are evident in the modulation of evoked responses by cortical state. A number of recent studies across different modalities have demonstrated that the patterns of activity in neuronal populations can vary strongly between synchronized and desynchronized cortical states, i.e., in the presence or absence of intrinsically generated up and down states. Here we investigated the impact of cortical state on the population coding of tones and speech in the primary auditory cortex (A1) of gerbils, and found that responses were qualitatively different in synchronized and desynchronized cortical states. Activity in synchronized A1 was only weakly modulated by sensory input, and the spike patterns evoked by tones and speech were unreliable and constrained to a small range of patterns. In contrast, responses to tones and speech in desynchronized A1 were temporally precise and reliable across trials, and different speech tokens evoked diverse spike patterns with extremely weak noise correlations, allowing responses to be decoded with nearly perfect accuracy. Restricting the analysis of synchronized A1 to activity within up states yielded similar results, suggesting that up states are not equivalent to brief periods of desynchronization. These findings demonstrate that the representational capacity of A1 depends strongly on cortical state, and suggest that cortical state should be considered as an explicit variable in all studies of sensory processing.

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12/05/13 | Extracting regions of interest from biological images with convolutional sparse block coding.
Pachitariu M, Packer AM, Pettit N, Dalgleish H, Häusser M, Sahani M
Neural Information Processing Systems (NIPS 2013). 2013 Dec 05:

Biological tissue is often composed of cells with similar morphologies replicated throughout large volumes and many biological applications rely on the accurate identification of these cells and their locations from image data. Here we develop a generative model that captures the regularities present in images composed of repeating elements of a few different types. Formally, the model can be described as convolutional sparse block coding. For inference we use a variant of convolutional matching pursuit adapted to block-based representations. We extend the K-SVD learning algorithm to subspaces by retaining several principal vectors from the SVD decomposition instead of just one. Good models with little cross-talk between subspaces can be obtained by learning the blocks incrementally. We perform extensive experiments on simulated images and the inference algorithm consistently recovers a large proportion of the cells with a small number of false positives. We fit the convolutional model to noisy GCaMP6 two-photon images of spiking neurons and to Nissl-stained slices of cortical tissue and show that it recovers cell body locations without supervision. The flexibility of the block-based representation is reflected in the variability of the recovered cell shapes.

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12/05/13 | Recurrent linear models of simultaneously-recorded neural populations.
Pachitariu M, Petreska B, Sahani M
Neural Information Processing Systems (NIPS 2013). 2013 Dec 05:

Population neural recordings with long-range temporal structure are often best understood in terms of a shared underlying low-dimensional dynamical process. Advances in recording technology provide access to an ever larger fraction of the population, but the standard computational approaches available to identify the collective dynamics scale poorly with the size of the dataset. Here we describe a new, scalable approach to discovering the low-dimensional dynamics that underlie simultaneously recorded spike trains from a neural population. Our method is based on recurrent linear models (RLMs), and relates closely to timeseries models based on recurrent neural networks. We formulate RLMs for neural data by generalising the Kalman-filter-based likelihood calculation for latent linear dynamical systems (LDS) models to incorporate a generalised-linear observation process. We show that RLMs describe motor-cortical population data better than either directly-coupled generalised-linear models or latent linear dynamical system models with generalised-linear observations. We also introduce the cascaded linear model (CLM) to capture low-dimensional instantaneous correlations in neural populations. The CLM describes the cortical recordings better than either Ising or Gaussian models and, like the RLM, can be fit exactly and quickly. The CLM can also be seen as a generalization of a low-rank Gaussian model, in this case factor analysis. The computational tractability of the RLM and CLM allow both to scale to very high-dimensional neural data.

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01/23/13 | Regularization and nonlinearities for neural language models: when are they needed?
Pachitariu M, Sahani M
arXiv. 2013 Jan 23:arXiv:1301.5650

Neural language models (LMs) based on recurrent neural networks (RNN) are some of the most successful word and character-level LMs. Why do they work so well, in particular better than linear neural LMs? Possible explanations are that RNNs have an implicitly better regularization or that RNNs have a higher capacity for storing patterns due to their nonlinearities or both. Here we argue for the first explanation in the limit of little training data and the second explanation for large amounts of text data. We show state-of-the-art performance on the popular and small Penn dataset when RNN LMs are regularized with random dropout. Nonetheless, we show even better performance from a simplified, much less expressive linear RNN model without off-diagonal entries in the recurrent matrix. We call this model an impulse-response LM (IRLM). Using random dropout, column normalization and annealed learning rates, IRLMs develop neurons that keep a memory of up to 50 words in the past and achieve a perplexity of 102.5 on the Penn dataset. On two large datasets however, the same regularization methods are unsuccessful for both models and the RNN's expressivity allows it to overtake the IRLM by 10 and 20 percent perplexity, respectively. Despite the perplexity gap, IRLMs still outperform RNNs on the Microsoft Research Sentence Completion (MRSC) task. We develop a slightly modified IRLM that separates long-context units (LCUs) from short-context units and show that the LCUs alone achieve a state-of-the-art performance on the MRSC task of 60.8%. Our analysis indicates that a fruitful direction of research for neural LMs lies in developing more accessible internal representations, and suggests an optimization regime of very high momentum terms for effectively training such models.

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12/03/12 | Learning visual motion in recurrent neural networks.
Pachitariu M, Sahani M
Neural Information Processing Systems (NIPS 2012). 12/2003:

We present a dynamic nonlinear generative model for visual motion based on a latent representation of binary-gated Gaussian variables. Trained on sequences of images, the model learns to represent different movement directions in different variables. We use an online approximate-inference scheme that can be mapped to the dynamics of networks of neurons. Probed with drifting grating stimuli and moving bars of light, neurons in the model show patterns of responses analogous to those of direction-selective simple cells in primary visual cortex. Most model neurons also show speed tuning and respond equally well to a range of motion directions and speeds aligned to the constraint line of their respective preferred speed. We show how these computations are enabled by a specific pattern of recurrent connections learned by the model.

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