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      Scaling Properties of Dimensionality Reduction for Neural Populations and Network Models

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          Abstract

          Recent studies have applied dimensionality reduction methods to understand how the multi-dimensional structure of neural population activity gives rise to brain function. It is unclear, however, how the results obtained from dimensionality reduction generalize to recordings with larger numbers of neurons and trials or how these results relate to the underlying network structure. We address these questions by applying factor analysis to recordings in the visual cortex of non-human primates and to spiking network models that self-generate irregular activity through a balance of excitation and inhibition. We compared the scaling trends of two key outputs of dimensionality reduction—shared dimensionality and percent shared variance—with neuron and trial count. We found that the scaling properties of networks with non-clustered and clustered connectivity differed, and that the in vivo recordings were more consistent with the clustered network. Furthermore, recordings from tens of neurons were sufficient to identify the dominant modes of shared variability that generalize to larger portions of the network. These findings can help guide the interpretation of dimensionality reduction outputs in regimes of limited neuron and trial sampling and help relate these outputs to the underlying network structure.

          Author Summary

          We seek to understand how billions of neurons in the brain work together to give rise to everyday brain function. In most current experimental settings, we can only record from tens of neurons for a few hours at a time. A major question in systems neuroscience is whether our interpretation of how neurons interact would change if we monitor orders of magnitude more neurons and for substantially more time. In this study, we use realistic networks of model neurons, which allow us to analyze the activity from as many model neurons as we want for as long as we want. For these models, we found that we can identify the salient interactions among neurons and interpret their activity meaningfully within the range of neurons and recording time available in current experiments. Furthermore, we studied how the neural activity from the models reflects how the neurons are connected. These results help to guide the interpretation of analyses using populations of neurons in the context of the larger network to understand brain function.

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          Most cited references45

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          The importance of mixed selectivity in complex cognitive tasks.

          Single-neuron activity in the prefrontal cortex (PFC) is tuned to mixtures of multiple task-related aspects. Such mixed selectivity is highly heterogeneous, seemingly disordered and therefore difficult to interpret. We analysed the neural activity recorded in monkeys during an object sequence memory task to identify a role of mixed selectivity in subserving the cognitive functions ascribed to the PFC. We show that mixed selectivity neurons encode distributed information about all task-relevant aspects. Each aspect can be decoded from the population of neurons even when single-cell selectivity to that aspect is eliminated. Moreover, mixed selectivity offers a significant computational advantage over specialized responses in terms of the repertoire of input-output functions implementable by readout neurons. This advantage originates from the highly diverse nonlinear selectivity to mixtures of task-relevant variables, a signature of high-dimensional neural representations. Crucially, this dimensionality is predictive of animal behaviour as it collapses in error trials. Our findings recommend a shift of focus for future studies from neurons that have easily interpretable response tuning to the widely observed, but rarely analysed, mixed selectivity neurons.
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            Dynamics of sparsely connected networks of excitatory and inhibitory spiking neurons.

            N Brunel (2000)
            The dynamics of networks of sparsely connected excitatory and inhibitory integrate-and-fire neurons are studied analytically. The analysis reveals a rich repertoire of states, including synchronous states in which neurons fire regularly; asynchronous states with stationary global activity and very irregular individual cell activity; and states in which the global activity oscillates but individual cells fire irregularly, typically at rates lower than the global oscillation frequency. The network can switch between these states, provided the external frequency, or the balance between excitation and inhibition, is varied. Two types of network oscillations are observed. In the fast oscillatory state, the network frequency is almost fully controlled by the synaptic time scale. In the slow oscillatory state, the network frequency depends mostly on the membrane time constant. Finite size effects in the asynchronous state are also discussed.
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              Dimensionality reduction for large-scale neural recordings.

              Most sensory, cognitive and motor functions depend on the interactions of many neurons. In recent years, there has been rapid development and increasing use of technologies for recording from large numbers of neurons, either sequentially or simultaneously. A key question is what scientific insight can be gained by studying a population of recorded neurons beyond studying each neuron individually. Here, we examine three important motivations for population studies: single-trial hypotheses requiring statistical power, hypotheses of population response structure and exploratory analyses of large data sets. Many recent studies have adopted dimensionality reduction to analyze these populations and to find features that are not apparent at the level of individual neurons. We describe the dimensionality reduction methods commonly applied to population activity and offer practical advice about selecting methods and interpreting their outputs. This review is intended for experimental and computational researchers who seek to understand the role dimensionality reduction has had and can have in systems neuroscience, and who seek to apply these methods to their own data.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Comput Biol
                PLoS Comput. Biol
                plos
                ploscomp
                PLoS Computational Biology
                Public Library of Science (San Francisco, CA USA )
                1553-734X
                1553-7358
                December 2016
                7 December 2016
                : 12
                : 12
                : e1005141
                Affiliations
                [1 ]Center for the Neural Basis of Cognition, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
                [2 ]School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                [3 ]Department of Machine Learning, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
                [4 ]Center for Theoretical Neuroscience, Columbia University, New York City, New York, United States of America
                [5 ]Department of Mathematics, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                [6 ]Dominick Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America
                [7 ]Department of Ophthalmology and Vision Sciences, Albert Einstein College of Medicine, Bronx, New York, United States of America
                [8 ]Department of Systems and Computational Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America
                [9 ]Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                [10 ]Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                [11 ]Fox Center for Vision Restoration, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
                [12 ]Department of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
                [13 ]Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America
                The University of Texas at Austin, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                • Conceptualization: RCW BRC ALK BD MAS BMY.

                • Data curation: RCW BRC AK MAS BMY.

                • Formal analysis: RCW BRC MAS BMY.

                • Funding acquisition: RCW BRC ALK BD AK MAS BMY.

                • Investigation: RCW AK MAS BMY.

                • Methodology: RCW BRC ALK BD AK MAS BMY.

                • Project administration: RCW MAS BMY.

                • Resources: RCW ALK BD AK MAS BMY.

                • Software: RCW ALK BMY.

                • Supervision: MAS BMY.

                • Validation: RCW MAS BMY.

                • Visualization: RCW MAS BMY.

                • Writing – original draft: RCW MAS BMY.

                • Writing – review & editing: RCW BRC ALK BD AK MAS BMY.

                Author information
                http://orcid.org/0000-0001-9558-9513
                http://orcid.org/0000-0003-2422-6576
                http://orcid.org/0000-0003-1192-9942
                Article
                PCOMPBIOL-D-16-00731
                10.1371/journal.pcbi.1005141
                5142778
                27926936
                c6b5f15e-9f08-4836-9bd6-02b0be5f01b5
                © 2016 Williamson et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 May 2016
                : 11 September 2016
                Page count
                Figures: 9, Tables: 0, Pages: 27
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: GM008208
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: DA022762
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: F32DC014387
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: EY016774
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: EY022928
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: P30EY008098
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000121, Division of Mathematical Sciences;
                Award ID: 1313225
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000121, Division of Mathematical Sciences;
                Award ID: 1517082
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000915, Richard King Mellon Foundation;
                Award Recipient :
                Funded by: National Defense Science and Engineering Graduate Fellowship
                Award ID: 32 CFR 168a
                Award Recipient :
                Funded by: Irma T. Hirschl Career Scientist Award
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100001818, Research to Prevent Blindness;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100001818, Research to Prevent Blindness;
                Award Recipient :
                Funded by: Simons Foundation Collaboration on the Global Brain
                Award Recipient :
                Funded by: Simons Foundation Collaboration on the Global Brain
                Award Recipient :
                Funded by: Simons Foundation Collaboration on the Global Brain
                Award Recipient :
                Funded by: Simons Foundation Collaboration on the Global Brain
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100001607, Eye and Ear Foundation of Pittsburgh;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008047, Carnegie Mellon University;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008047, Carnegie Mellon University;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100008047, Carnegie Mellon University;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000071, National Institute of Child Health and Human Development;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000001, National Science Foundation;
                Award ID: BCS-1533672
                Award Recipient :
                RCW is supported by National Institute of Drug Abuse (NIDA, https://www.drugabuse.gov/, DA022762), National Institute of General Medical Sciences (NIGMS, https://www.nigms.nih.gov/, GM008208), and a Richard King Mellon Foundation ( http://foundationcenter.org/grantmaker/rkmellon/) Presidential Fellowship in the Life Sciences. BRC is supported by National Defense Science and Engineering Graduate Fellowship ( https://ndseg.asee.org/, 32 CFR 168a). ALK, BD, AK, and BMY are supported by Simons Foundation ( https://www.simonsfoundation.org/, 325293, 364994). ALK is also supported by NIH National Institute on Deafness and Other Communication Disorders (NIDCD, https://www.nidcd.nih.gov/, F32DC014387). BD, MAS, and BMY are supported by a Carnegie Mellon University ProSEED / Brainhub seed grant. BD is also supported by National Science Foundation (NSF, http://www.nsf.gov/, DMS-1313225, DMS-1517082). AK and MAS are supported by National Eye Institute (NEI, https://nei.nih.gov/, EY016774, EY022928, P30EY008098) and Research to Prevent Blindness ( https://www.rpbusa.org/). AK is also supported by a Irma T. Hirschl Career Scientist Award ( https://www.einstein.yu.edu/administration/grant-support/Hirschl.aspx). MAS is also supported by Eye and Ear Foundation of Pittsburgh ( http://eyeandear.org/). BMY is also supported by National Institute of Child Health and Human Development (NICHD, https://www.nichd.nih.gov/, HD071686) and National Science Foundation (NSF, http://www.nsf.gov/, BCS-1533672). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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                Custom metadata
                All neural recordings are publicly available in the following repository: http://doi.org/10.6080/K0NC5Z4X. Code for simulating the network models can be found at http://www.columbia.edu/~ak3625/index.shtml.

                Quantitative & Systems biology
                Quantitative & Systems biology

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