Abstract
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.
Highlights
Jefferys [1] defined population electric field effects as those “in which the synchronous activity of populations of neurons causes large electric fields that can affect the excitability of suitably oriented, but not closely neighboring, neurons”
We first review converging evidence from in-vitro and in-vivo studies that suggest the former, and using realistic finite element modeling, we show that the electric fields generated by transcranial electrical current stimulation are of the same magnitude as endogenous ones in this scale
Frohlich et al [3] showed that exogenous direct current (DC) and low frequency alternating current (AC) electric fields modulate neocortical network activity in slices with a threshold of 0.5 V/m
Summary
Jefferys [1] defined population electric field effects as those “in which the synchronous activity of populations of neurons causes large electric fields that can affect the excitability of suitably oriented, but not closely neighboring, neurons”. Frohlich et al [3] showed that exogenous direct current (DC) and low frequency alternating current (AC) electric fields modulate neocortical network activity in slices with a threshold of 0.5 V/m They found effects from the application of exogenous fields mimicking endogenous fields recorded from the slices. More recent research has further established the role of ephaptic interactions and the sensitivity of neuronal populations to weak fields both in-vitro and in-silico It demonstrates that endogenous fields are capable of mediating the propagation of self-regenerating slow (*0.1 m/s) neural waves [4,5] and that externally applied extracellular electric fields with amplitudes in the range of endogenous fields are sufficient to modulate or block the propagation of this activity both in vitro and in silico models [6]. Table B in S1 Text provides an overview spanning six decades of in-vivo and in-vitro research on the physiological impact of weak, low frequency (< 100 Hz) electric fields—both exogenous and endogenous
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