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      Imaging Cerebral Activity in Amyotrophic Lateral Sclerosis

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          Advances in neuroimaging, complementing histopathological insights, have established a multi-system involvement of cerebral networks beyond the traditional neuromuscular pathological view of amyotrophic lateral sclerosis (ALS). The development of effective disease-modifying therapy remains a priority and this will be facilitated by improved biomarkers of motor system integrity against which to assess the efficacy of candidate drugs. Functional MRI (FMRI) is an established measure of both cerebral activity and connectivity, but there is an increasing recognition of neuronal oscillations in facilitating long-distance communication across the cortical surface. Such dynamic synchronization vastly expands the connectivity foundations defined by traditional neuronal architecture. This review considers the unique pathogenic insights afforded by the capture of cerebral disease activity in ALS using FMRI and encephalography.

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          Most cited references 167

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          Event-related EEG/MEG synchronization and desynchronization: basic principles.

          An internally or externally paced event results not only in the generation of an event-related potential (ERP) but also in a change in the ongoing EEG/MEG in form of an event-related desynchronization (ERD) or event-related synchronization (ERS). The ERP on the one side and the ERD/ERS on the other side are different responses of neuronal structures in the brain. While the former is phase-locked, the latter is not phase-locked to the event. The most important difference between both phenomena is that the ERD/ERS is highly frequency band-specific, whereby either the same or different locations on the scalp can display ERD and ERS simultaneously. Quantification of ERD/ERS in time and space is demonstrated on data from a number of movement experiments.
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            Neurodegenerative diseases target large-scale human brain networks.

            During development, the healthy human brain constructs a host of large-scale, distributed, function-critical neural networks. Neurodegenerative diseases have been thought to target these systems, but this hypothesis has not been systematically tested in living humans. We used network-sensitive neuroimaging methods to show that five different neurodegenerative syndromes cause circumscribed atrophy within five distinct, healthy, human intrinsic functional connectivity networks. We further discovered a direct link between intrinsic connectivity and gray matter structure. Across healthy individuals, nodes within each functional network exhibited tightly correlated gray matter volumes. The findings suggest that human neural networks can be defined by synchronous baseline activity, a unified corticotrophic fate, and selective vulnerability to neurodegenerative illness. Future studies may clarify how these complex systems are assembled during development and undermined by disease.
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              Rhythms for Cognition: Communication through Coherence.

               Pascal Fries (2015)
              I propose that synchronization affects communication between neuronal groups. Gamma-band (30-90 Hz) synchronization modulates excitation rapidly enough that it escapes the following inhibition and activates postsynaptic neurons effectively. Synchronization also ensures that a presynaptic activation pattern arrives at postsynaptic neurons in a temporally coordinated manner. At a postsynaptic neuron, multiple presynaptic groups converge, e.g., representing different stimuli. If a stimulus is selected by attention, its neuronal representation shows stronger and higher-frequency gamma-band synchronization. Thereby, the attended stimulus representation selectively entrains postsynaptic neurons. The entrainment creates sequences of short excitation and longer inhibition that are coordinated between pre- and postsynaptic groups to transmit the attended representation and shut out competing inputs. The predominantly bottom-up-directed gamma-band influences are controlled by predominantly top-down-directed alpha-beta-band (8-20 Hz) influences. Attention itself samples stimuli at a 7-8 Hz theta rhythm. Thus, several rhythms and their interplay render neuronal communication effective, precise, and selective.

                Author and article information

                Front Neurol
                Front Neurol
                Front. Neurol.
                Frontiers in Neurology
                Frontiers Media S.A.
                08 January 2019
                : 9
                1Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford, United Kingdom
                2Computational Neuroimaging Group, Academic Unit of Neurology, Trinity College Dublin , Dublin, Ireland
                3Wellcome Centre for Integrative Neuroimaging, University of Oxford , Oxford, United Kingdom
                Author notes

                Edited by: Francesca Trojsi, Università Degli Studi Della Campania “Luigi Vanvitelli” Naples, Italy

                Reviewed by: Edoardo Gioele Spinelli, Vita-Salute San Raffaele University, Italy; Rodolfo Gabriel Gatto, University of Illinois at Chicago, United States

                *Correspondence: Martin R. Turner martin.turner@

                This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neurology

                Copyright © 2019 Proudfoot, Bede and Turner.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 167, Pages: 13, Words: 11003
                Funded by: Health Research Board 10.13039/100010414
                Funded by: Irish Institute of Clinical Neuroscience 10.13039/501100003840
                Funded by: Iris O'Brien Foundation 10.13039/100013029
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