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      Basis profile curve identification to understand electrical stimulation effects in human brain networks

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          Abstract

          Brain networks can be explored by delivering brief pulses of electrical current in one area while measuring voltage responses in other areas. We propose a convergent paradigm to study brain dynamics, focusing on a single brain site to observe the average effect of stimulating each of many other brain sites. Viewed in this manner, visually-apparent motifs in the temporal response shape emerge from adjacent stimulation sites. This work constructs and illustrates a data-driven approach to determine characteristic spatiotemporal structure in these response shapes, summarized by a set of unique “basis profile curves” (BPCs). Each BPC may be mapped back to underlying anatomy in a natural way, quantifying projection strength from each stimulation site using simple metrics. Our technique is demonstrated for an array of implanted brain surface electrodes in a human patient. This framework enables straightforward interpretation of single-pulse brain stimulation data, and can be applied generically to explore the diverse milieu of interactions that comprise the connectome.

          Author summary

          We present a new machine learning framework to probe how brain regions interact using single-pulse electrical stimulation. Unlike previous studies, this approach does not assume a form for how one brain area will respond to stimulation in another area, but rather discovers the shape of the response in time from the data. We call the set of characteristic discovered response shapes “basis profile curves” (BPCs), and show how these can be mapped back onto the brain quantitatively. An illustrative example is included from one of our human patients to characterize inputs to the parahippocampal gyrus. A code package is downloadable from https://purl.stanford.edu/rc201dv0636 so the reader may explore the technique with their own data, or study sample data provided to reproduce the illustrative case presented in the manuscript.

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          Most cited references41

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          A multi-modal parcellation of human cerebral cortex

          Understanding the amazingly complex human cerebral cortex requires a map (or parcellation) of its major subdivisions, known as cortical areas. Making an accurate areal map has been a century-old objective in neuroscience. Using multi-modal magnetic resonance images from the Human Connectome Project (HCP) and an objective semi-automated neuroanatomical approach, we delineated 180 areas per hemisphere bounded by sharp changes in cortical architecture, function, connectivity, and/or topography in a precisely aligned group average of 210 healthy young adults. We characterized 97 new areas and 83 areas previously reported using post-mortem microscopy or other specialized study-specific approaches. To enable automated delineation and identification of these areas in new HCP subjects and in future studies, we trained a machine-learning classifier to recognize the multi-modal ‘fingerprint’ of each cortical area. This classifier detected the presence of 96.6% of the cortical areas in new subjects, replicated the group parcellation, and could correctly locate areas in individuals with atypical parcellations. The freely available parcellation and classifier will enable substantially improved neuroanatomical precision for studies of the structural and functional organization of human cerebral cortex and its variation across individuals and in development, aging, and disease.
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            Learning the parts of objects by non-negative matrix factorization.

            Is perception of the whole based on perception of its parts? There is psychological and physiological evidence for parts-based representations in the brain, and certain computational theories of object recognition rely on such representations. But little is known about how brains or computers might learn the parts of objects. Here we demonstrate an algorithm for non-negative matrix factorization that is able to learn parts of faces and semantic features of text. This is in contrast to other methods, such as principal components analysis and vector quantization, that learn holistic, not parts-based, representations. Non-negative matrix factorization is distinguished from the other methods by its use of non-negativity constraints. These constraints lead to a parts-based representation because they allow only additive, not subtractive, combinations. When non-negative matrix factorization is implemented as a neural network, parts-based representations emerge by virtue of two properties: the firing rates of neurons are never negative and synaptic strengths do not change sign.
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              An Introduction to the Bootstrap

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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ResourcesRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Funding acquisitionRole: InvestigationRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Comput Biol
                PLoS Comput Biol
                plos
                PLoS Computational Biology
                Public Library of Science (San Francisco, CA USA )
                1553-734X
                1553-7358
                September 2021
                2 September 2021
                : 17
                : 9
                : e1008710
                Affiliations
                [1 ] Department of Neurological Surgery, Mayo Clinic, Rochester, Minnesota, United States of America
                [2 ] Department of Biomedical Engineering & Physiology, Mayo Clinic, Rochester, Minnesota, United States of America
                [3 ] Google Research, Brain Team, Berlin, Germany
                [4 ] Machine Learning Group, Department of Computer Science, Berlin Institute of Technology, Berlin, Germany
                [5 ] Department of Artificial Intelligence, Korea University, Seoul, Republic of Korea
                [6 ] Max Planck Institute for Informatics, Saarbrücken, Germany
                University of Groningen, NETHERLANDS
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-6687-6422
                https://orcid.org/0000-0002-3861-7685
                https://orcid.org/0000-0002-8683-8909
                Article
                PCOMPBIOL-D-21-00124
                10.1371/journal.pcbi.1008710
                8412306
                34473701
                67c026b2-4030-4d51-a199-e5f823936ed9
                © 2021 Miller 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
                : 26 January 2021
                : 21 July 2021
                Page count
                Figures: 4, Tables: 0, Pages: 20
                Funding
                Funded by: Van Wagenen Society
                Award Recipient :
                Funded by: Brain Research Foundation (US)
                Award ID: Fay/Frank Seed Grant
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000874, Brain and Behavior Research Foundation;
                Award ID: NARSAD Young Investigator Grant
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: NCATS CTSA KL2 TR002379
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: NIMH CRCNS R01MH122258-01
                Award Recipient :
                Funded by: institute of information & communications technology planning & evaluation
                Award ID: 2017-0-00451
                Award Recipient :
                Funded by: institute of information & communications technology planning & evaluation
                Award ID: 2019-0-00079
                Award Recipient :
                Funded by: German Ministry for Education and Research
                Award ID: 01IS14013A-E, 01GQ1115, 01GQ0850, 01IS18025A, 031L0207D, 01IS18037A
                Award Recipient :
                Funded by: German Research Foundation
                Award ID: Math+, EXC 2046/1, Project ID 390685689
                Award Recipient :
                KJM was supported by the Van Wagenen Fellowship, the Brain Research Foundation with a Fay/Frank Seed Grant, and the Brain & Behavior Research Foundation with a NARSAD Young Investigator Grant. This work was also supported by NIH-NCATS CTSA KL2 TR002379 (KJM). DH was supported by the NIH-NIMH CRCNS R01MH122258-01. Manuscript contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. KRM was supported in part by the Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea Government (No. 2017-0-00451, Development of BCI based Brain and Cognitive Computing Technology for Recognizing User’s Intentions using Deep Learning) and (No. 2019-0-00079, Artificial Intelligence Graduate School Program, Korea University), and by the German Ministry for Education and Research (BMBF) under Grants 01IS14013A-E, 01GQ1115, 01GQ0850, 01IS18025A, 031L0207D and 01IS18037A; the German Research Foundation (DFG) under Grant Math+, EXC 2046/1, Project ID 390685689. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Functional Electrical Stimulation
                Physical Sciences
                Chemistry
                Electrochemistry
                Electrode Potentials
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Membrane Potential
                Evoked Potentials
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Neurophysiology
                Evoked Potentials
                Biology and Life Sciences
                Neuroscience
                Neurophysiology
                Evoked Potentials
                Physical Sciences
                Mathematics
                Statistics
                Statistical Noise
                Computer and Information Sciences
                Neural Networks
                Biology and Life Sciences
                Neuroscience
                Neural Networks
                Biology and Life Sciences
                Physiology
                Electrophysiology
                Biology and Life Sciences
                Neuroscience
                Brain Mapping
                Electrocorticography
                Research and Analysis Methods
                Imaging Techniques
                Neuroimaging
                Electrocorticography
                Biology and Life Sciences
                Neuroscience
                Neuroimaging
                Electrocorticography
                Engineering and Technology
                Signal Processing
                Signal to Noise Ratio
                Custom metadata
                Code written in MATLAB to reproduce all of the steps and illustrations contained in this manuscript is freely available along with the sample dataset at https://purl.stanford.edu/rc201dv0636, for use without restriction.

                Quantitative & Systems biology
                Quantitative & Systems biology

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