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  1. Article: The neurobiology of functional neurological disorders characterised by impaired awareness.

    Milano, Beatrice Annunziata / Moutoussis, Michael / Convertino, Laura

    Frontiers in psychiatry

    2023  Volume 14, Page(s) 1122865

    Abstract: We review the neurobiology of Functional Neurological Disorders (FND), i.e., neurological disorders not explained by currently identifiable histopathological processes, in order to focus on those characterised by impaired awareness (functionally impaired ...

    Abstract We review the neurobiology of Functional Neurological Disorders (FND), i.e., neurological disorders not explained by currently identifiable histopathological processes, in order to focus on those characterised by impaired awareness (functionally impaired awareness disorders, FIAD), and especially, on the paradigmatic case of Resignation Syndrome (RS). We thus provide an improved more integrated theory of FIAD, able to guide both research priorities and the diagnostic formulation of FIAD. We systematically address the diverse spectrum of clinical presentations of FND with impaired awareness, and offer a new framework for understanding FIAD. We find that unraveling the historical development of neurobiological theory of FIAD is of paramount importance for its current understanding. Then, we integrate contemporary clinical material in order to contextualise the neurobiology of FIAD within social, cultural, and psychological perspectives. We thus review neuro-computational insights in FND in general, to arrive at a more coherent account of FIAD. FIAD may be based on maladaptive predictive coding, shaped by stress, attention, uncertainty, and, ultimately, neurally encoded beliefs and their updates. We also critically appraise arguments in support of and against such Bayesian models. Finally, we discuss implications of our theoretical account and provide pointers towards an improved clinical diagnostic formulation of FIAD. We suggest directions for future research towards a more unified theory on which future interventions and management strategies could be based, as effective treatments and clinical trial evidence remain limited.
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Systematic Review
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2023.1122865
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  2. Article ; Online: Association cortical areas in the mouse contain a large population of fast-spiking GABAergic neurons that do not express parvalbumin.

    Courcelles, Erik Justin / Kjelsberg, Kasper / Convertino, Laura / Nair, Rajeevkumar Raveendran / Witter, Menno P / Nigro, Maximiliano José

    The European journal of neuroscience

    2024  

    Abstract: GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin-expressing fast-spiking ... ...

    Abstract GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin-expressing fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the density of parvalbumin interneurons has been shown to be lower in associative areas of the mouse cortex as compared with sensory and motor areas. Modelling work based on these quantifications linked the low-density of parvalbumin interneurons with specific computations of associative cortices. However, it is still unknown whether the total GABAergic population of association cortices is smaller or whether another GABAergic type can compensate for the low density of parvalbumin interneurons. In the present study, we investigated these hypotheses using a combination of neuroanatomy, mouse genetics and neurophysiology. We found that the GABAergic population of association areas is comparable with that of primary sensory areas, and it is enriched of fast-spiking neurons that do not express parvalbumin and were not accounted for by previous quantifications. We developed an intersectional viral strategy to demonstrate that the population of fast-spiking neurons is comparable across cortical regions. Our results provide quantifications of the density of fast-spiking GABAergic neurons and offers new biological constrains to refine current models of cortical computations.
    Language English
    Publishing date 2024-04-21
    Publishing country France
    Document type Journal Article
    ZDB-ID 645180-9
    ISSN 1460-9568 ; 0953-816X
    ISSN (online) 1460-9568
    ISSN 0953-816X
    DOI 10.1111/ejn.16341
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2548: Show issues Location:
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  3. Article: Synthetic Spatial Foraging With Active Inference in a Geocaching Task.

    Neacsu, Victorita / Convertino, Laura / Friston, Karl J

    Frontiers in neuroscience

    2022  Volume 16, Page(s) 802396

    Abstract: Humans are highly proficient in learning about the environments in which they operate. They form flexible spatial representations of their surroundings that can be leveraged with ease during spatial foraging and navigation. To capture these abilities, we ...

    Abstract Humans are highly proficient in learning about the environments in which they operate. They form flexible spatial representations of their surroundings that can be leveraged with ease during spatial foraging and navigation. To capture these abilities, we present a deep Active Inference model of goal-directed behavior, and the accompanying belief updating. Active Inference rests upon optimizing Bayesian beliefs to maximize model evidence or marginal likelihood. Bayesian beliefs are probability distributions over the causes of observable outcomes. These causes include an agent's actions, which enables one to treat planning as inference. We use simulations of a geocaching task to elucidate the belief updating-that underwrites spatial foraging-and the associated behavioral and neurophysiological responses. In a geocaching task, the aim is to find hidden objects in the environment using spatial coordinates. Here, synthetic agents learn about the environment via inference and learning (e.g., learning about the likelihoods of outcomes given latent states) to reach a target location, and then forage locally to discover the hidden object that offers clues for the next location.
    Language English
    Publishing date 2022-02-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2411902-7
    ISSN 1662-453X ; 1662-4548
    ISSN (online) 1662-453X
    ISSN 1662-4548
    DOI 10.3389/fnins.2022.802396
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  4. Article ; Online: Cancer Niches and Their Kikuchi Free Energy.

    Sajid, Noor / Convertino, Laura / Friston, Karl

    Entropy (Basel, Switzerland)

    2021  Volume 23, Issue 5

    Abstract: Biological forms depend on a progressive specialization of pluripotent stem cells. The differentiation of these cells in their spatial and functional environment defines the organism itself; however, cellular mutations may disrupt the mutual balance ... ...

    Abstract Biological forms depend on a progressive specialization of pluripotent stem cells. The differentiation of these cells in their spatial and functional environment defines the organism itself; however, cellular mutations may disrupt the mutual balance between a cell and its niche, where cell proliferation and specialization are released from their autopoietic homeostasis. This induces the construction of cancer niches and maintains their survival. In this paper, we characterise cancer niche construction as a direct consequence of interactions between clusters of cancer and healthy cells. Explicitly, we evaluate these higher-order interactions between niches of cancer and healthy cells using Kikuchi approximations to the free energy. Kikuchi's free energy is measured in terms of changes to the sum of energies of baseline clusters of cells (or nodes) minus the energies of overcounted cluster intersections (and interactions of interactions, etc.). We posit that these changes in energy node clusters correspond to a long-term reduction in the complexity of the system conducive to cancer niche survival. We validate this formulation through numerical simulations of apoptosis, local cancer growth, and metastasis, and highlight its implications for a computational understanding of the etiopathology of cancer.
    Language English
    Publishing date 2021-05-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2014734-X
    ISSN 1099-4300 ; 1099-4300
    ISSN (online) 1099-4300
    ISSN 1099-4300
    DOI 10.3390/e23050609
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  5. Article ; Online: Reduced grid-like theta modulation in schizophrenia.

    Convertino, Laura / Bush, Daniel / Zheng, Fanfan / Adams, Rick A / Burgess, Neil

    Brain : a journal of neurology

    2022  Volume 146, Issue 5, Page(s) 2191–2198

    Abstract: The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex and reduced theta coherence with medial prefrontal ... ...

    Abstract The hippocampal formation has been implicated in the pathophysiology of schizophrenia, with patients showing impairments in spatial and relational cognition, structural changes in entorhinal cortex and reduced theta coherence with medial prefrontal cortex. Both the entorhinal cortex and medial prefrontal cortex exhibit a 6-fold (or 'hexadirectional') modulation of neural activity during virtual navigation that is indicative of grid cell populations and associated with accurate spatial navigation. Here, we examined whether these grid-like patterns are disrupted in schizophrenia. We asked 17 participants with diagnoses of schizophrenia and 23 controls (matched for age, sex and IQ) to perform a virtual reality spatial navigation task during magnetoencephalography. The control group showed stronger 4-10 Hz theta power during movement onset, as well as hexadirectional modulation of theta band oscillatory activity in the right entorhinal cortex whose directional stability across trials correlated with navigational accuracy. This hexadirectional modulation was absent in schizophrenia patients, with a significant difference between groups. These results suggest that impairments in spatial and relational cognition associated with schizophrenia may arise from disrupted grid firing patterns in entorhinal cortex.
    MeSH term(s) Humans ; Schizophrenia ; Theta Rhythm/physiology ; Entorhinal Cortex ; Grid Cells/physiology ; Hippocampus
    Language English
    Publishing date 2022-11-08
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awac416
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    In stock of ZB MED Cologne/Königswinter

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  6. Article ; Online: Markov blankets in the brain.

    Hipólito, Inês / Ramstead, Maxwell J D / Convertino, Laura / Bhat, Anjali / Friston, Karl / Parr, Thomas

    Neuroscience and biobehavioral reviews

    2021  Volume 125, Page(s) 88–97

    Abstract: Recent characterisations of self-organising systems depend upon the presence of a 'Markov blanket': a statistical boundary that mediates the interactions between the inside and outside of a system. We leverage this idea to provide an analysis of ... ...

    Abstract Recent characterisations of self-organising systems depend upon the presence of a 'Markov blanket': a statistical boundary that mediates the interactions between the inside and outside of a system. We leverage this idea to provide an analysis of partitions in neuronal systems. This is applicable to brain architectures at multiple scales, enabling partitions into single neurons, brain regions, and brain-wide networks. This treatment is based upon the canonical micro-circuitry used in empirical studies of effective connectivity, so as to speak directly to practical applications. The notion of effective connectivity depends upon the dynamic coupling between functional units, whose form recapitulates that of a Markov blanket at each level of analysis. The nuance afforded by partitioning neural systems in this way highlights certain limitations of 'modular' perspectives of brain function that only consider a single level of description.
    MeSH term(s) Brain ; Brain Mapping ; Humans
    Language English
    Publishing date 2021-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 282464-4
    ISSN 1873-7528 ; 0149-7634
    ISSN (online) 1873-7528
    ISSN 0149-7634
    DOI 10.1016/j.neubiorev.2021.02.003
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1371: Show issues Location:
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  7. Book ; Online: Markov Blankets in the Brain

    Hipolito, Ines / Ramstead, Maxwell / Convertino, Laura / Bhat, Anjali / Friston, Karl / Parr, Thomas

    2020  

    Abstract: Recent characterisations of self-organising systems depend upon the presence of a Markov blanket: a statistical boundary that mediates the interactions between what is inside of and outside of a system. We leverage this idea to provide an analysis of ... ...

    Abstract Recent characterisations of self-organising systems depend upon the presence of a Markov blanket: a statistical boundary that mediates the interactions between what is inside of and outside of a system. We leverage this idea to provide an analysis of partitions in neuronal systems. This is applicable to brain architectures at multiple scales, enabling partitions into single neurons, brain regions, and brain-wide networks. This treatment is based upon the canonical micro-circuitry used in empirical studies of effective connectivity, so as to speak directly to practical applications. This depends upon the dynamic coupling between functional units, whose form recapitulates that of a Markov blanket at each level. The nuance afforded by partitioning neural systems in this way highlights certain limitations of modular perspectives of brain function that only consider a single level of description.

    Comment: 25 pages, 5 figures, 1 table, Glossary
    Keywords Quantitative Biology - Neurons and Cognition ; Physics - Biological Physics
    Subject code 612
    Publishing date 2020-06-04
    Publishing country us
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Computational Modeling of Electroencephalography and Functional Magnetic Resonance Imaging Paradigms Indicates a Consistent Loss of Pyramidal Cell Synaptic Gain in Schizophrenia.

    Adams, Rick A / Pinotsis, Dimitris / Tsirlis, Konstantinos / Unruh, Leonhardt / Mahajan, Aashna / Horas, Ana Montero / Convertino, Laura / Summerfelt, Ann / Sampath, Hemalatha / Du, Xiaoming Michael / Kochunov, Peter / Ji, Jie Lisa / Repovs, Grega / Murray, John D / Friston, Karl J / Hong, L Elliot / Anticevic, Alan

    Biological psychiatry

    2021  Volume 91, Issue 2, Page(s) 202–215

    Abstract: Background: Diminished synaptic gain-the sensitivity of postsynaptic responses to neural inputs-may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or ... ...

    Abstract Background: Diminished synaptic gain-the sensitivity of postsynaptic responses to neural inputs-may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms.
    Methods: People with schizophrenia diagnoses (PScz) (n = 108), their relatives (n = 57), and control subjects (n = 107) underwent 3 electroencephalography (EEG) paradigms-resting, mismatch negativity, and 40-Hz auditory steady-state response-and resting functional magnetic resonance imaging. Dynamic causal modeling was used to quantify synaptic connectivity in cortical microcircuits.
    Results: Classic group differences in EEG features between PScz and control subjects were replicated, including increased theta and other spectral changes (resting EEG), reduced mismatch negativity, and reduced 40-Hz power. Across all 4 paradigms, characteristic PScz data features were all best explained by models with greater self-inhibition (decreased synaptic gain) in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in PScz in 3 paradigms.
    Conclusions: First, characteristic EEG changes in PScz in 3 classic paradigms are all attributable to the same underlying parameter change: greater self-inhibition in pyramidal cells. Second, psychotic symptoms in PScz relate to disinhibition in neural circuits. These findings are more commensurate with the hypothesis that in PScz, a primary loss of synaptic gain on pyramidal cells is then compensated by interneuron downregulation (rather than the converse). They further suggest that psychotic symptoms relate to this secondary downregulation.
    MeSH term(s) Computer Simulation ; Electroencephalography ; Evoked Potentials, Auditory ; Humans ; Magnetic Resonance Imaging ; Pyramidal Cells ; Schizophrenia/diagnostic imaging
    Language English
    Publishing date 2021-08-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 209434-4
    ISSN 1873-2402 ; 0006-3223
    ISSN (online) 1873-2402
    ISSN 0006-3223
    DOI 10.1016/j.biopsych.2021.07.024
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