Neuromodulation of Axon Terminals

Cerebral Cortex, 2017; 1–9 doi: 10.1093/cercor/bhx158   Download PDF:NeuromodulationofAxons

Darpan Chakraborty, Dennis Q. Truong, Marom Bikson and Hanoch Kaphzan


Abstract: Understanding which cellular compartments are influenced during neuromodulation underpins any rational effort to explain and optimize outcomes. Axon terminals have long been speculated to be sensitive to polarization, but experimentally informed models for CNS stimulation are lacking. We conducted simultaneous intracellular recording from the neuron soma and axon terminal (blebs) during extracellular stimulation with weak sustained (DC) uniform electric fields in mouse cortical slices. Use of weak direct current stimulation (DCS) allowed isolation and quantification of changes in axon terminal biophysics, relevant to both suprathreshold (e.g., deep brain stimulation, spinal cord stimulation, and transcranial magnetic stimulation) and subthreshold (e.g., transcranial DCS and transcranial alternating current stimulation) neuromodulation approaches. Axon terminals polarized with sensitivity (mV of membrane polarization per V/ m electric field) 4 times than somas. Even weak polarization (<2 mV) of axon terminals significantly changes action potential dynamics (including amplitude, duration, conduction velocity) in response to an intracellular pulse. Regarding a cellular theory of neuromodulation, we explain how suprathreshold CNS stimulation activates the action potential at terminals while subthreshold approaches modulate synaptic efficacy through axon terminal polarization. We demonstrate that by virtue of axon polarization and resulting changes in action potential dynamics, neuromodulation can influence analog– digital information processing.

2017 Brain Stimulation and Imaging Meeting, Vancouver Canada, June 23-24

Meeting website link

June 24: 1:45 PM
Lucas Parra, Professor of Biomedical Engineering, The City College of the City University of New York Center for Discovery and Innovation, New York, NY, USA

Watch excerpts form the talk here and here

June 24: 2:15 PM
Marom Bikson, Professor of Biomedical Engineering at The City College of New York (CCNY) of the City University of New York (CUNY) and co-Director of the Neural Engineering Group at the New York Center for Biomedical Engineering

Download Bikson slides: BrainStim2017_final

Friday 6/23 at 3 pm in CDI 3rd floor conference room (3.352)

Laurent Koessler from CNRS and Lorraine University will be speaking
Title:  Brain source detection and localization using multi-scale EEG recording.
Abstract: In drug-resistant epilepsy surgery investigations, epileptogenic zone and brain functional areas localization are required. This localization relies on scalp and intracerebral EEG recordings. In Nancy (France) I developed a program concerning simultaneous scalp and intracerebral EEG recordings. Using this methodological approach, 1) in vivo human brain tissue conductivities can be estimated, 2) relationship from brain sources to scalp EEG correlates can be studied and 3) non invasive electrical source localization can be validated.
Tomorrow June 21st at 2pm in CDI 3rd floor conference room (3.352)
Bashar Badran from the Medical Universty of South Carolina and University of New Mexico will be speaking

Title: Development, optimization, and neurophysiological effects of transcutaneous auricular vagus nerve stimulation (taVNS)

Abstract: taVNS is an emerging new form of neuromodulation involving transcutaneous electrical stimulation of the auricular branch of the vagus nerve. Still in its infancy and showing much clinical promise, the optimal human stimulation parameters and direct brain effects are undetermined. This lecture will present the findings of two important studies that aim to solve the taVNS problem of infinite parametric solutions. The first, a taVNS parametric study exploring 9 different combinations of pulse width and frequency and their activation of the vagal tone as measured by physiological recordings. The second is a novel multi-modal imaging study that establishes concurrent taVNS/fMRI and explores the direct brain effect of taVNS on the human brain’s BOLD response. These findings aim to establish an aim and direction of the optimal taVNS parameters to guide future trials.

Neuroimage. 2017 May 31;157:69-80. doi: 10.1016/j.neuroimage.2017.05.059.

Optimal use of EEG recordings to target active brain areas with transcranial electrical stimulation.

Dmochowski JP, Koessler L, Norcia AM, Bikson M, Parra LC.

Full paper: OptimalUseEEG_2016

Abstract: To demonstrate causal relationships between brain and behavior, investigators would like to guide brain stimulation using measurements of neural activity. Particularly promising in this context are electroencephalography (EEG) and transcranial electrical stimulation (TES), as they are linked by a reciprocity principle which, despite being known for decades, has not led to a formalism for relating EEG recordings to optimal stimulation parameters. Here we derive a closed-form expression for the TES configuration that optimally stimulates (i.e., targets) the sources of recorded EEG, without making assumptions about source location or distribution. We also derive a duality between TES targeting and EEG source localization, and demonstrate that in cases where source localization fails, so does the proposed targeting. Numerical simulations with multiple head models confirm these theoretical predictions and quantify the achieved stimulation in terms of focality and intensity. We show that constraining the stimulation currents automatically selects optimal montages that involve only a few (4-7) electrodes, with only incremental loss in performance when targeting focal activations. The proposed technique allows brain scientists and clinicians to rationally target the sources of observed EEG and thus overcomes a major obstacle to the realization of individualized or closed-loop brain stimulation.

“Noninvasive Neuromodulation Goes Deep” Jacek Dmochowski and Marom Bikson, Cell.

Modulating deep regions of the brain with noninvasive technology has challenged researchers for decades. In a new study, Grossman et al. leverage the emergence of a slowly oscillating ‘‘beat’’ from intersecting high-frequency electric fields to stimulate deep brain regions, opening a frontier in the biophysics and technology of brain stimulation. Download PDF: FullPaper