Double transcranial direct current stimulation of the brain increases cerebral energy levels and systemic glucose tolerance in men

Abstract

Transcranial direct current stimulation (tDCS) is a neuromodulatory method that has been tested experimentally and has already been used as an adjuvant therapeutic option to treat a number of neurological disorders and neuropsychiatric diseases. Beyond its well known local effects within the brain, tDCS also transiently promotes systemic glucose uptake and reduces the activity of the neurohormonal stress axes. We aimed to test whether the effects of a single tDCS application could be replicated upon double stimulation to persistently improve systemic glucose tolerance and stress axes activity in humans. In a single‐blinded cross‐over study, we examined 15 healthy male volunteers. Anodal tDCS vs sham was applied twice in series. Systemic glucose tolerance was investigated by the standard hyperinsulinaemic‐euglycaemic glucose clamp procedure, and parameters of neurohormonal stress axes activity were measured. Because tDCS‐induced brain energy consumption has been shown to be part of the mechanism underlying the assumed effects, we monitored the cerebral high‐energy phosphates ATP and phosphocreatine by 31phosphorus magnetic resonance spectroscopy. As hypothesised, analyses revealed that double anodal tDCS persistently increases glucose tolerance compared to sham. Moreover, we observed a significant rise in cerebral high‐energy phosphate content upon double tDCS. Accordingly, the activity of the neurohormonal stress axes was reduced upon tDCS compared to sham. Our data demonstrate that double tDCS promotes systemic glucose uptake and reduces stress axes activity in healthy humans. These effects suggest that repetitive tDCS may be a future non‐pharmacological option for combating glucose intolerance in type 2 diabetes patients.

Magnetic resonance spectroscopy with transcranial direct current stimulation to explore the underlying biochemical and physiological mechanism of the human brain: A systematic review

“…T A B L E 3 MR system, MRS parameters and MRS fitting software Rae et al, 2013;Rango et al, 2008;Ryan et al, 2018;Siniatchkin et al, 2012;Tremblay et al, 2014Tremblay et al, , 2016Wardzinski et al, 2019;Wilke et al, 2017;Zappasodi et al, 2018) dealing with human subjects were selected for the review. Figure 1 is a flow diagram summarising the inclusion process of the studies.…”

“…Table 6 shows a symbolised neurometabolite concentration modulation of all neurometabolites in the different areas of the brain in the healthy subjects measured following tDCS. Jalali et al 2018 Right temporal cortex Barron et al 2018Koolschijn et al 2019 Right supplementary motor cortex Ryan et al 2018 Right motor cortex Bachtiar et al 2018Binkofski et al 2011Carlson et al 2018* Jauch-Chara et al 2015Kistenmacher et al 2017Nwaroh et al 2020Rango et al 2018Tremblay et al 2015Wardzinski et al 2019 Visual cortex Siniatchnik et al 2011 Right parietal cortex Clark et al 2011 Right DLPFC Dickler et al 2018Hone-Blanchet et al 2016Rae et al 2013 Left DLPFC Dickler et al 2018Hone-Blanchet et al 2016Rae et al 2013 Left motor cortex Antonenko et al 2017Auvichayapat et al 2017, 2018Bachtiar et al 2018Bachtiar et al 2016Carlson et al 2018* Kim et al 2014Patel et al Ryan et al Stagg et al 2009, 2011Tremblay et al 2015Wilke et al 2017Zappasodi et al 2018 Left IFG Harris et al 2019 Left pSTG Dwyer et al 2019 F I G U R E 3 Brain regions where tDCS was applied with their corresponding published articles and literature included in this review. Colour coding indicates one study per colour, which used the bi-hemispheric stimulation.…”

The Onset of Diabetes During Transcranial Direct Current Stimulation Treatment of Anorexia Nervosa — A Case Report

“…Wardzinski et al (28) successfully increased the systemic glucose tolerance and cerebral high-energy phosphate content by utilizing the anodal stimulation of the right motor area (C4) with the cathode over Fp1. A protocol of 2 sessions of 1 mA tDCS lasting 20 min was used.…”

Lactate infusion increases brain energy content during euglycemia but not hypoglycemia in healthy men

“…However, at 3.0 T, as applied in our study, the limited bandwidth of the excitation pulse leads to a slightly lower β‐ATP peak. Therefore, ATP was calculated as the sum of α‐, β‐ and γ‐ATP, which also allows for comparisons with previous work that proceeded identically . PCr represents a high energy reservoir linked to ATP in a bidirectional reaction, in which ATP is formed by PCr and vice versa, catalyzed by the creatine‐phosphokinase at a 1: 1 (PCr: ATP) molar ratio.…”

“…Therefore, ATP was calculated as the sum of α-, βand γ-ATP, which also allows for comparisons with previous work that proceeded identically. [22][23][24] PCr represents a high energy reservoir linked to ATP in a bidirectional reaction, in which ATP is formed by PCr and vice versa, catalyzed by the creatine-phosphokinase at a 1: 1 (PCr: ATP) molar ratio. Because the balance of this reaction prefers ATP formation, the energy demands of cells are initially satisfied by a shift in this equilibrium.…”