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Realistic modeling of mesoscopic ephaptic coupling in the human brain.

PLoS Computational Biology. 2020;16(6):e1007923 DOI 10.1371/journal.pcbi.1007923


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Journal Title: PLoS Computational Biology

ISSN: 1553-734X (Print); 1553-7358 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Science: Biology (General)

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML



Giulio Ruffini

Ricardo Salvador

Ehsan Tadayon

Roser Sanchez-Todo

Alvaro Pascual-Leone

Emiliano Santarnecchi


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Time From Submission to Publication: 32 weeks


Abstract | Full Text

Several decades of research suggest that weak electric fields may influence neural processing, including those induced by neuronal activity and proposed as a substrate for a potential new cellular communication system, i.e., ephaptic transmission. Here we aim to model mesoscopic ephaptic activity in the human brain and explore its trajectory during aging by characterizing the electric field generated by cortical dipoles using realistic finite element modeling. Extrapolating from electrophysiological measurements, we first observe that modeled endogenous field magnitudes are comparable to those in measurements of weak but functionally relevant self-generated fields and to those produced by noninvasive transcranial brain stimulation, and therefore possibly able to modulate neuronal activity. Then, to evaluate the role of these fields in the human cortex in large MRI databases, we adapt an interaction approximation that considers the relative orientation of neuron and field to estimate the membrane potential perturbation in pyramidal cells. We use this approximation to define a simplified metric (EMOD1) that weights dipole coupling as a function of distance and relative orientation between emitter and receiver and evaluate it in a sample of 401 realistic human brain models from healthy subjects aged 16-83. Results reveal that ephaptic coupling, in the simplified mesoscopic modeling approach used here, significantly decreases with age, with higher involvement of sensorimotor regions and medial brain structures. This study suggests that by providing the means for fast and direct interaction between neurons, ephaptic modulation may contribute to the complexity of human function for cognition and behavior, and its modification across the lifespan and in response to pathology.