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      Demixed principal component analysis of neural population data

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          Abstract

          Neurons in higher cortical areas, such as the prefrontal cortex, are often tuned to a variety of sensory and motor variables, and are therefore said to display mixed selectivity. This complexity of single neuron responses can obscure what information these areas represent and how it is represented. Here we demonstrate the advantages of a new dimensionality reduction technique, demixed principal component analysis (dPCA), that decomposes population activity into a few components. In addition to systematically capturing the majority of the variance of the data, dPCA also exposes the dependence of the neural representation on task parameters such as stimuli, decisions, or rewards. To illustrate our method we reanalyze population data from four datasets comprising different species, different cortical areas and different experimental tasks. In each case, dPCA provides a concise way of visualizing the data that summarizes the task-dependent features of the population response in a single figure.

          DOI: http://dx.doi.org/10.7554/eLife.10989.001

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          Many neuroscience experiments today involve using electrodes to record from the brain of an animal, such as a mouse or a monkey, while the animal performs a task. The goal of such experiments is to understand how a particular brain region works. However, modern experimental techniques allow the activity of hundreds of neurons to be recorded simultaneously. Analysing such large amounts of data then becomes a challenge in itself.

          This is particularly true for brain regions such as the prefrontal cortex that are involved in the cognitive processes that allow an animal to acquire knowledge. Individual neurons in the prefrontal cortex encode many different types of information relevant to a given task. Imagine, for example, that an animal has to select one of two objects to obtain a reward. The same group of prefrontal cortex neurons will encode the object presented to the animal, the animal’s decision and its confidence in that decision. This simultaneous representation of different elements of a task is called a ‘mixed’ representation, and is difficult to analyse.

          Kobak, Brendel et al. have now developed a data analysis tool that can ‘demix’ neural activity. The tool breaks down the activity of a population of neurons into its individual components. Each of these relates to only a single aspect of the task and is thus easier to interpret. Information about stimuli, for example, is distinguished from information about the animal’s confidence levels.

          Kobak, Brendel et al. used the demixing tool to reanalyse existing datasets recorded from several different animals, tasks and brain regions. In each case, the tool provided a complete, concise and transparent summary of the data. The next steps will be to apply the analysis tool to new datasets to see how well it performs in practice. At a technical level, the tool could also be extended in a number of different directions to enable it to deal with more complicated experimental designs in future.

          DOI: http://dx.doi.org/10.7554/eLife.10989.002

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          Most cited references43

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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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            Neural population dynamics during reaching

            Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from an analogous approach to primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well that analogy holds. Single-neuron responses in motor cortex appear strikingly complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. We found that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behavior. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate unexpected yet surprisingly simple structure in the population response. That underlying structure explains many of the confusing features of individual-neuron responses.
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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: Reviewing editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                12 April 2016
                2016
                : 5
                : e10989
                Affiliations
                [1 ]deptChampalimaud Neuroscience Program , Champalimaud Centre for the Unknown , Lisbon, Portugal
                [2 ]École Normale Supérieure , Paris, France
                [3 ]Centre for Integrative Neuroscience, University of Tübingen , Tübingen, Germany
                [4 ]Wake Forest University School of Medicine , Winston-Salem, United States
                [5 ]Cold Spring Harbor Laboratory , Cold Spring Harbor, United States
                [6 ]deptInstituto de Fisiología Celular-Neurociencias , Universidad Nacional Autónoma de México , Mexico City, Mexico
                [7 ]El Colegio Nacional , Mexico City, Mexico
                [8 ]Harvard University , Cambridge, United States
                [9]University of Edinburgh , United Kingdom
                [10]University of Edinburgh , United Kingdom
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-5639-7209
                http://orcid.org/0000-0002-8002-922X
                Article
                10989
                10.7554/eLife.10989
                4887222
                27067378
                d610a823-76cd-4396-a069-c40c8108034c
                © 2016, Kobak et al

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 19 August 2015
                : 07 April 2016
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005032, Fundação Bial;
                Award ID: Fellowship, 389/14
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                2.5
                A new data analysis tool provides a concise way of visualizing neural data that summarizes all the relevant features of the population response in a single figure.

                Life sciences
                prefrontal cortex,principal component analysis,dimensionality reduction,population activity,rat,other,rhesus macaque

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