Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation
Abstract
Transcranial electric stimulation aims to stimulate the brain by applying weak electrical currents at the scalp. However, the magnitude and spatial distribution of electric fields in the human brain are unknown. We measured electric potentials intracranially in ten epilepsy patients and estimate electric fields across the entire brain by leveraging calibrated current-flow models. When stimulating at 2 mA, cortical electric fields reach 0.4 V/m, the lower limit of effectiveness in animal studies. When individual whole-head anatomy is considered, the predicted electric field magnitudes correlate with the recorded values in cortical (r=0.89) and depth (r=0.84) electrodes. Accurate models require adjustment of tissue conductivity values reported in the literature, but accuracy is not improved when incorporating white matter anisotropy or different skull compartments. This is the first study to validate and calibrate current-flow models with in vivo intracranial recordings in humans, providing a solid foundation to target stimulation and interpret clinical trials.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke
- Yu Huang
- Anli A Liu
- Belen Lafon
- Daniel Friedman
- Michael Dayan
- Xiuyuan Wang
- Marom Bikson
- Werner K Doyle
- Orrin Devinsky
- Lucas C Parra
National Institute of Mental Health
- Yu Huang
- Anli A Liu
- Belen Lafon
- Daniel Friedman
- Michael Dayan
- Xiuyuan Wang
- Marom Bikson
- Werner K Doyle
- Orrin Devinsky
- Lucas C Parra
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Richard Ivry, University of California, Berkeley, United States
Ethics
Human subjects: This study was performed at the New York University Medical Center (NYUMC). The protocol was approved by the NYUMC Institutional Review Board(IRB) and all patients provided written informed consent prior to their participation in the study. A physician was present at the bedside during the entire procedure to monitor for clinical safety.
Version history
- Received: June 16, 2016
- Accepted: February 6, 2017
- Accepted Manuscript published: February 7, 2017 (version 1)
- Version of Record published: March 28, 2017 (version 2)
- Version of Record updated: February 15, 2018 (version 3)
Copyright
© 2017, Huang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further reading
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Alternative RNA splicing is an essential and dynamic process in neuronal differentiation and synapse maturation, and dysregulation of this process has been associated with neurodegenerative diseases. Recent studies have revealed the importance of RNA-binding proteins in the regulation of neuronal splicing programs. However, the molecular mechanisms involved in the control of these splicing regulators are still unclear. Here, we show that KIS, a kinase upregulated in the developmental brain, imposes a genome-wide alteration in exon usage during neuronal differentiation in mice. KIS contains a protein-recognition domain common to spliceosomal components and phosphorylates PTBP2, counteracting the role of this splicing factor in exon exclusion. At the molecular level, phosphorylation of unstructured domains within PTBP2 causes its dissociation from two co-regulators, Matrin3 and hnRNPM, and hinders the RNA-binding capability of the complex. Furthermore, KIS and PTBP2 display strong and opposing functional interactions in synaptic spine emergence and maturation. Taken together, our data uncover a post-translational control of splicing regulators that link transcriptional and alternative exon usage programs in neuronal development.