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  1. Book ; Online: Brain as a complex system, harnessing systems neuroscience tools & notions for an empirical approach

    Safavi, Shervin

    2023  

    Abstract: Finding general principles underlying brain function has been appealing to scientists. Indeed, in some branches of science like physics and chemistry (and to some degree biology) a general theory often can capture the essence of a wide range of phenomena. ...

    Abstract Finding general principles underlying brain function has been appealing to scientists. Indeed, in some branches of science like physics and chemistry (and to some degree biology) a general theory often can capture the essence of a wide range of phenomena. Whether we can find such principles in neuroscience, and [assuming they do exist] what those principles are, are important questions. Abstracting the brain as a complex system is one of the perspectives that may help us answer this question. While it is commonly accepted that the brain is a (or even the) prominent example of a complex system, the far reaching implications of this are still arguably overlooked in our approaches to neuroscientific questions. One of the reasons for the lack of attention could be the apparent difference in foci of investigations in these two fields -- neuroscience and complex systems. This thesis is an effort toward providing a bridge between systems neuroscience and complex systems by harnessing systems neuroscience tools & notions for building empirical approaches toward the brain as a complex system. Perhaps, in the spirit of searching for principles, we should abstract and approach the brain as a complex adaptive system as the more complete perspective (rather than just a complex system). In the end, the brain, even the most "complex system", need to survive in the environment. Indeed, in the field of complex adaptive systems, the intention is understanding very similar questions in nature. As an outlook, we also touch on some research directions pertaining to the adaptivity of the brain as well.

    Comment: PhD thesis. Complete thesis is available here https://tobias-lib.ub.uni-tuebingen.de/xmlui/handle/10900/128071
    Keywords Quantitative Biology - Neurons and Cognition
    Subject code 501
    Publishing date 2023-12-20
    Publishing country us
    Document type Book ; Online
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  2. Article ; Online: Multistability, perceptual value, and internal foraging.

    Safavi, Shervin / Dayan, Peter

    Neuron

    2022  Volume 110, Issue 19, Page(s) 3076–3090

    Abstract: Substantial experimental, theoretical, and computational insights into sensory processing have been derived from the phenomena of perceptual multistability-when two or more percepts alternate or switch in response to a single sensory input. Here, we ... ...

    Abstract Substantial experimental, theoretical, and computational insights into sensory processing have been derived from the phenomena of perceptual multistability-when two or more percepts alternate or switch in response to a single sensory input. Here, we review a range of findings suggesting that alternations can be seen as internal choices by the brain responding to values. We discuss how elements of external, experimenter-controlled values and internal, uncertainty- and aesthetics-dependent values influence multistability. We then consider the implications for the involvement in switching of regions, such as the anterior cingulate cortex, which are more conventionally tied to value-dependent operations such as cognitive control and foraging.
    MeSH term(s) Brain/physiology ; Uncertainty ; Vision, Binocular/physiology ; Visual Perception/physiology
    Language English
    Publishing date 2022-08-29
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2022.07.024
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  3. Article ; Online: From Univariate to Multivariate Coupling Between Continuous Signals and Point Processes: A Mathematical Framework.

    Safavi, Shervin / Logothetis, Nikos K / Besserve, Michel

    Neural computation

    2021  Volume 33, Issue 7, Page(s) 1751–1817

    Abstract: Time series data sets often contain heterogeneous signals, composed of both continuously changing quantities and discretely occurring events. The coupling between these measurements may provide insights into key underlying mechanisms of the systems under ...

    Abstract Time series data sets often contain heterogeneous signals, composed of both continuously changing quantities and discretely occurring events. The coupling between these measurements may provide insights into key underlying mechanisms of the systems under study. To better extract this information, we investigate the asymptotic statistical properties of coupling measures between continuous signals and point processes. We first introduce martingale stochastic integration theory as a mathematical model for a family of statistical quantities that include the phase locking value, a classical coupling measure to characterize complex dynamics. Based on the martingale central limit theorem, we can then derive the asymptotic gaussian distribution of estimates of such coupling measure that can be exploited for statistical testing. Second, based on multivariate extensions of this result and random matrix theory, we establish a principled way to analyze the low-rank coupling between a large number of point processes and continuous signals. For a null hypothesis of no coupling, we establish sufficient conditions for the empirical distribution of squared singular values of the matrix to converge, as the number of measured signals increases, to the well-known Marchenko-Pastur (MP) law, and the largest squared singular value converges to the upper end of the MP support. This justifies a simple thresholding approach to assess the significance of multivariate coupling. Finally, we illustrate with simulations the relevance of our univariate and multivariate results in the context of neural time series, addressing how to reliably quantify the interplay between multichannel local field potential signals and the spiking activity of a large population of neurons.
    MeSH term(s) Mathematics ; Models, Theoretical ; Neurons
    Language English
    Publishing date 2021-08-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1025692-1
    ISSN 1530-888X ; 0899-7667
    ISSN (online) 1530-888X
    ISSN 0899-7667
    DOI 10.1162/neco_a_01389
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  4. Book ; Online ; Thesis: Brain as a Complex System, harnessing systems neuroscience tools & notions for an empirical approach

    Safavi, Shervin [Verfasser] / Logothetis, Nikos K. [Gutachter]

    2022  

    Author's details Shervin Safavi ; Gutachter: Nikos K. Logothetis
    Keywords Naturwissenschaften ; Science
    Subject code sg500
    Language English
    Publisher Universitätsbibliothek Tübingen
    Publishing place Tübingen
    Document type Book ; Online ; Thesis
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  5. Article ; Online: Uncovering the organization of neural circuits with Generalized Phase Locking Analysis.

    Safavi, Shervin / Panagiotaropoulos, Theofanis I / Kapoor, Vishal / Ramirez-Villegas, Juan F / Logothetis, Nikos K / Besserve, Michel

    PLoS computational biology

    2023  Volume 19, Issue 4, Page(s) e1010983

    Abstract: Despite the considerable progress of in vivo neural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high ... ...

    Abstract Despite the considerable progress of in vivo neural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high dimensional functional connectivity measures to mechanistic models of network activity. We address this issue by investigating spike-field coupling (SFC) measurements, which quantify the synchronization between, on the one hand, the action potentials produced by neurons, and on the other hand mesoscopic "field" signals, reflecting subthreshold activities at possibly multiple recording sites. As the number of recording sites gets large, the amount of pairwise SFC measurements becomes overwhelmingly challenging to interpret. We develop Generalized Phase Locking Analysis (GPLA) as an interpretable dimensionality reduction of this multivariate SFC. GPLA describes the dominant coupling between field activity and neural ensembles across space and frequencies. We show that GPLA features are biophysically interpretable when used in conjunction with appropriate network models, such that we can identify the influence of underlying circuit properties on these features. We demonstrate the statistical benefits and interpretability of this approach in various computational models and Utah array recordings. The results suggest that GPLA, used jointly with biophysical modeling, can help uncover the contribution of recurrent microcircuits to the spatio-temporal dynamics observed in multi-channel experimental recordings.
    MeSH term(s) Nerve Net/physiology ; Models, Neurological ; Neurons/physiology ; Action Potentials/physiology
    Language English
    Publishing date 2023-04-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2193340-6
    ISSN 1553-7358 ; 1553-734X
    ISSN (online) 1553-7358
    ISSN 1553-734X
    DOI 10.1371/journal.pcbi.1010983
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  6. Article ; Online: Bistability of prefrontal states gates access to consciousness.

    Dwarakanath, Abhilash / Kapoor, Vishal / Werner, Joachim / Safavi, Shervin / Fedorov, Leonid A / Logothetis, Nikos K / Panagiotaropoulos, Theofanis I

    Neuron

    2023  Volume 111, Issue 10, Page(s) 1666–1683.e4

    Abstract: Access of sensory information to consciousness has been linked to the ignition of content-specific representations in association cortices. How does ignition interact with intrinsic cortical state fluctuations to give rise to conscious perception? We ... ...

    Abstract Access of sensory information to consciousness has been linked to the ignition of content-specific representations in association cortices. How does ignition interact with intrinsic cortical state fluctuations to give rise to conscious perception? We addressed this question in the prefrontal cortex (PFC) by combining multi-electrode recordings with a binocular rivalry (BR) paradigm inducing spontaneously driven changes in the content of consciousness, inferred from the reflexive optokinetic nystagmus (OKN) pattern. We find that fluctuations between low-frequency (LF, 1-9 Hz) and beta (∼20-40 Hz) local field potentials (LFPs) reflect competition between spontaneous updates and stability of conscious contents, respectively. Both LF and beta events were locally modulated. The phase of the former locked differentially to the competing populations just before a spontaneous transition while the latter synchronized the neuronal ensemble coding the consciously perceived content. These results suggest that prefrontal state fluctuations gate conscious perception by mediating internal states that facilitate perceptual update and stability.
    MeSH term(s) Visual Perception/physiology ; Consciousness/physiology ; Prefrontal Cortex/physiology ; Cerebral Cortex ; Nystagmus, Optokinetic
    Language English
    Publishing date 2023-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2023.02.027
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  7. Book ; Online: From univariate to multivariate coupling between continuous signals and point processes

    Safavi, Shervin / Logothetis, Nikos K. / Besserve, Michel

    a mathematical framework

    2020  

    Abstract: Time series datasets often contain heterogeneous signals, composed of both continuously changing quantities and discretely occurring events. The coupling between these measurements may provide insights into key underlying mechanisms of the systems under ... ...

    Abstract Time series datasets often contain heterogeneous signals, composed of both continuously changing quantities and discretely occurring events. The coupling between these measurements may provide insights into key underlying mechanisms of the systems under study. To better extract this information, we investigate the asymptotic statistical properties of coupling measures between continuous signals and point processes. We first introduce martingale stochastic integration theory as a mathematical model for a family of statistical quantities that include the Phase Locking Value, a classical coupling measure to characterize complex dynamics. Based on the martingale Central Limit Theorem, we can then derive the asymptotic Gaussian distribution of estimates of such coupling measure, that can be exploited for statistical testing. Second, based on multivariate extensions of this result and Random Matrix Theory, we establish a principled way to analyze the low rank coupling between a large number of point processes and continuous signals. For a null hypothesis of no coupling, we establish sufficient conditions for the empirical distribution of squared singular values of the matrix to converge, as the number of measured signals increases, to the well-known Marchenko-Pastur (MP) law, and the largest squared singular value converges to the upper end of the MPs support. This justifies a simple thresholding approach to assess the significance of multivariate coupling. Finally, we illustrate with simulations the relevance of our univariate and multivariate results in the context of neural time series, addressing how to reliably quantify the interplay between multi channel Local Field Potential signals and the spiking activity of a large population of neurons.

    Comment: 50 pages
    Keywords Statistics - Methodology ; Quantitative Biology - Neurons and Cognition ; Statistics - Applications
    Subject code 510
    Publishing date 2020-05-08
    Publishing country us
    Document type Book ; Online
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  8. Article ; Online: Decoding internally generated transitions of conscious contents in the prefrontal cortex without subjective reports.

    Kapoor, Vishal / Dwarakanath, Abhilash / Safavi, Shervin / Werner, Joachim / Besserve, Michel / Panagiotaropoulos, Theofanis I / Logothetis, Nikos K

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 1535

    Abstract: A major debate about the neural correlates of conscious perception concerns its cortical organization, namely, whether it includes the prefrontal cortex (PFC), which mediates executive functions, or it is constrained within posterior cortices. It has ... ...

    Abstract A major debate about the neural correlates of conscious perception concerns its cortical organization, namely, whether it includes the prefrontal cortex (PFC), which mediates executive functions, or it is constrained within posterior cortices. It has been suggested that PFC activity during paradigms investigating conscious perception is conflated with post-perceptual processes associated with reporting the contents of consciousness or feedforward signals originating from exogenous stimulus manipulations and relayed via posterior cortical areas. We addressed this debate by simultaneously probing neuronal populations in the rhesus macaque (Macaca mulatta) PFC during a no-report paradigm, capable of instigating internally generated transitions in conscious perception, without changes in visual stimulation. We find that feature-selective prefrontal neurons are modulated concomitantly with subjective perception and perceptual suppression of their preferred stimulus during both externally induced and internally generated changes in conscious perception. Importantly, this enables reliable single-trial, population decoding of conscious contents. Control experiments confirm significant decoding of stimulus contents, even when oculomotor responses, used for inferring perception, are suppressed. These findings suggest that internally generated changes in the contents of conscious visual perception are reliably reflected within the activity of prefrontal populations in the absence of volitional reports or changes in sensory input.
    MeSH term(s) Animals ; Consciousness/physiology ; Macaca mulatta ; Photic Stimulation ; Prefrontal Cortex/physiology ; Visual Perception/physiology
    Language English
    Publishing date 2022-03-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-28897-2
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  9. Article: Bistability of prefrontal states gates access to consciousness

    Dwarakanath, Abhilash / Kapoor, Vishal / Werner, Joachim / Safavi, Shervin / Fedorov, Leonid A. / Logothetis, Nikos K. / Panagiotaropoulos, Theofanis I.

    Neuron

    2023  Volume 111, Issue 10, Page(s) 1666–1683

    Abstract: Abstract not released by publisher. ...

    Title translation Bistabilität von präfrontalen Zuständen ermöglicht Zugang zum Bewusstsein
    Abstract Abstract not released by publisher.
    Keywords Affen ; Awareness ; Beta Rhythm ; Beta-Rhythmus ; Bewusstheit ; Bewusstseinszustände ; Binocular Vision ; Binokulares Sehen ; Consciousness States ; Electrical Activity ; Elektrische Aktivität ; Monkeys ; Nystagmus ; Prefrontal Cortex ; Präfrontaler Kortex ; Visual Perception ; Visuelle Wahrnehmung
    Language English
    Document type Article
    ZDB-ID 808167-0
    ISSN 1097-4199 ; 0896-6273
    ISSN (online) 1097-4199
    ISSN 0896-6273
    DOI 10.1016/j.neuron.2023.02.027
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  10. Article: Is the frontal lobe involved in conscious perception?

    Safavi, Shervin / Kapoor, Vishal / Logothetis, Nikos K / Panagiotaropoulos, Theofanis I

    Frontiers in psychology

    2014  Volume 5, Page(s) 1063

    Language English
    Publishing date 2014-09-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2563826-9
    ISSN 1664-1078
    ISSN 1664-1078
    DOI 10.3389/fpsyg.2014.01063
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