Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: A standardized low resolution tomography (sLORETA) study
Research Highlights
► Prefrontal tDCS (tDCS) reduces slow-wave activity. ► Prefrontal RtDCS tend to increase high-frequency activity. ► Prefrontal rtDCS improves performance (errors, accuracy) in a working memory task (n-back). ► This is accompanied by P2- and P3-amplitude increases. ► And by an increased left parahippocampal activity (sLORETA).
Introduction
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method that shifts neuronal resting membrane potentials towards depolarization or hyperpolarization, depending on whether anodal or cathodal stimulation is applied, leading to changes of cortical excitability and other functional parameters (Nitsche et al., 2008, Nitsche et al., 2003a, Nitsche et al., 2003b). More recently, Nitsche and Paulus, 2000, Nitsche and Paulus, 2001 revisited this approach in humans and demonstrated that anodal tDCS increases and cathodal tDCS decreases motor cortex excitability (Nitsche and Paulus, 2000, Nitsche and Paulus, 2001). When applied for 9–13 min, tDCS produces post-stimulation effects in the human motor cortex that are stable for up to 1 h and longer (Nitsche et al., 2003c, Nitsche and Paulus, 2001). As demonstrated in animal experiments, the primary mechanism of tDCS appears to be a subthreshold modulation of neuronal resting membrane potential (Purpura and McMurtry, 1965). Accordingly, pharmacologically blocking voltage-dependent ion channels in humans abolishes any effect of depolarizing anodal tDCS on cortical excitability, but does not influence the impact of hyperpolarizing cathodal tDCS (Nitsche et al., 2003a). Pharmacological studies have proven that tDCS related effects depend on changes of NMDA receptor-efficacy (Liebetanz et al., 2002). Recently, Stagg et al. (2009) demonstrated changes in GABA levels after anodal tDCS using magnetic resonance spectroscopy (MRS), suggesting that anodal excitatory effects do affect GABAergic inhibition in addition to NMDA-receptor dependency (Stagg et al., 2009). Based on initial studies, combining tDCS and EEG, a direct impact of tDCS on oscillatory activity was observed (Ardolino et al., 2005, Marshall et al., 2004). During slow-wave sleep (SWS) bilateral frontal sinusoidal anodal tDCS reduced the average power in the theta and alpha-1-bands in frontal, central and parietal electrode locations (Marshall et al., 2004). Compared to placebo stimulation, frontal anodal tDCS during SWS-rich sleep distinctly increased the retention of word pairs (Marshall et al., 2004). Ardolino et al. (2005) also found a widespread impact of tDCS on the EEG (Ardolino et al., 2005). Increasing amounts of delta and theta activity were found after cathodal DC stimulation (15 min, 1.5 mA) to the right motor cortex, extending beyond the primary stimulation site (Ardolino et al., 2005). These EEG pilot studies are indicative of possible large-scale network changes following tDCS. Using positron emission tomography, Lang et al. (2005) showed that anodal tDCS increased the rCBF in widespread cortical and subcortical areas in comparison to cathodal tDCS, while cathodal stimulation entailed an excitability decrease of the metabolic activity in the corresponding areas (Lang et al., 2005).
One mode of tDCS application, namely anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) and cathodal stimulation of the right supraorbital region, has been associated with working memory enhancement and improvement in other cognitive domains (Boggio et al., 2006, Dockery et al., 2009, Elmer et al., 2009, Ferrucci et al., 2008, Fertonani et al., 2010, Fiori et al., 2010, Fregni et al., 2005, Kincses et al., 2004, Marshall et al., 2004, Ohn et al., 2008).
Memory processes of healthy subjects were enhanced after left anodal DLPFC tDCS with the cathode placed on the right frontocortical regions (Fregni et al., 2005, Kincses et al., 2004, Marshall et al., 2004, Marshall et al., 2005, Ohn et al., 2008). Moreover, prefrontal tDCS is supposed to modulate pain perception (Boggio et al., 2009, Boggio et al., 2008b), seems to influence social behavior (Knoch et al., 2008) and shows an impact on risk taking behavior (Beeli et al., 2008a, Beeli et al., 2008b, Fecteau et al., 2007a, Fecteau et al., 2007b). Prefrontal tDCS may even influence the desire for specific foods (Fregni et al., 2008) and the reaction time to lies (Priori et al., 2008).
In depressed subjects promising pilot data of prefrontal tDCS were reported, suggesting a therapeutic action of real tDCS compared to sham tDCS (Boggio et al., 2007, Boggio et al., 2008a, Ferrucci et al., 2009, Fregni et al., 2006, Rigonatti et al., 2008), whereas the effect of one single tDCS-session on healthy subjects had no mood-altering effects (Koenigs et al., 2009).
The mechanism of action of prefrontal tDCS is not completely understood and to date there has been no study about the effects of prefrontal tDCS on resting EEG. Moreover, as prefrontal tDCS seems to influence a wide range of disorders and behaviors, resting state EEG and source analysis techniques may help to better understand prefrontal tDCS induced post-stimulation effects. Furthermore, TMS, MRS and imaging studies are only an indirect proof of the neuronal activity and were predominantly applied to the motor cortex in the past to test the effects of tDCS on brain physiology. We therefore investigated the effects of anodal tDCS of the left DLPFC and cathodal tDCS of the supraorbital region in a placebo-controlled cross-over study in healthy subjects, applying resting state EEG with spectral power analysis and standardized low resolution tomography (sLORETA). Following resting-state EEG all healthy subjects underwent a working memory task (n-back) with event-related potential (ERP) recording. As prefrontal tDCS has been found to influence working memory performance, we intended to replicate this behavioral finding and hypothesized that neurophysiological correlates should be detectable in ERPs related to cognitive processes.
Section snippets
Subjects
Ten healthy subjects (five women, five men, mean age = 28.89 years, SD = 2.67) participated in this study. All subjects underwent a semi-structured interview (including the M-CIDI-S interview and a semantic word fluency task (Wittchen and Müller, 1998) showing that they were without history of neurological and/or psychiatric diseases and free of medication affecting the central nervous system. All subjects were right-handed (Edinburgh handedness test (Oldfield, 1971)) and homogenous with regard to
Distinguishability of DC stimulators
All subjects were asked if they perceived a difference between the stimulation conditions and if they could specifically discern real from placebo tDCS. Nobody was able to distinguish real and sham tDCS, nor did the reported sensations differ between stimulation conditions.
Mood changes
No side effects of stimulation were reported. There were no significant differences in the PANAS before and after tDCS (see Table 1). The Positive Affect Scale showed no main effects for time (F(1,9) = 0.02, p = 0.96, n.s.) and
EEG study
Our results suggest that anodal tDCS above the left DLPFC with the cathode placed supraorbitally on the contralateral side may influence regional electrical activity in the surface EEG and deeper in the prefrontal lobe as revealed by sLORETA. However, the underlying mechanisms are not well understood and several hypotheses might be discussed, e.g. neuroplastic effects by prolonged weak depolarization/hyperpolarization, effects on connected networks or even brain conductivity heterogeneities.
As
Acknowledgments
This study is part of the Ph.D. thesis of Daniel Keeser at the Faculty of Medicine of the Ludwig-Maximilians University of Munich (in preparation). We gratefully acknowledge T. Sprenger for his invaluable advise, and thank M. Hartmann, D. Bars und H.J. Engelbregt for critically reading our manuscript.
References (100)
- et al.
EEG differences in children between eyes-closed and eyes-open resting conditions
Clin. Neurophysiol.
(2009) - et al.
Effects of transcranial direct current stimulation on working memory in patients with Parkinson's disease
J. Neurol. Sci.
(2006) - et al.
Go-no-go task performance improvement after anodal transcranial DC stimulation of the left dorsolateral prefrontal cortex in major depression
J. Affect. Disord.
(2007) - et al.
Modulation of emotions associated with images of human pain using anodal transcranial direct current stimulation (tDCS)
Neuropsychologia
(2009) - et al.
A parametric study of prefrontal cortex involvement in human working memory
Neuroimage
(1997) - et al.
Loss of control during instrumental learning: a source localization study
Neuroimage
(2010) - et al.
Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism
Eur. Neuropsychopharmacol.
(2002) - et al.
Transcranial direct current stimulation in severe, drug-resistant major depression
J. Affect. Disord.
(2009) - et al.
Naming facilitation induced by transcranial direct current stimulation
Behav. Brain Res.
(2010) - et al.
Transcranial direct current stimulation of the prefrontal cortex modulates the desire for specific foods
Appetite
(2008)
Dual pathways connecting the dorsolateral prefrontal cortex with the hippocampal formation and parahippocampal cortex in the rhesus monkey
Neuroscience
Generators of the late cognitive potentials in auditory and visual oddball tasks
Electroencephalogr. Clin. Neurophysiol.
Slow EEG pattern predicts reduced intrinsic functional connectivity in the default mode network: an inter-subject analysis
Neuroimage
Hemodynamic correlates of EEG: a heuristic
Neuroimage
Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism
Biol. Psychiatry
Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human
Neuropsychologia
Representations in human visual short-term memory: an event-related brain potential study
Neurosci. Lett.
Bilateral frontal transcranial direct current stimulation: failure to replicate classic findings in healthy subjects
Clin. Neurophysiol.
Cognitive effects of nicotine in humans: an fMRI study
Neuroimage
Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response
Biol. Psychiatry
Deep brain stimulation for treatment-resistant depression
Neuron
Antipsychotic effect of electroconvulsive therapy is related to normalization of subgenual cingulate theta activity in psychotic depression
J. Psychiatr. Res.
Integration of fMRI and simultaneous EEG: towards a comprehensive understanding of localization and time-course of brain activity in target detection
Neuroimage
Modulation of cortical excitability by weak direct current stimulation — technical, safety and functional aspects
Suppl. Clin. Neurophysiol.
Level of action of cathodal DC polarisation induced inhibition of the human motor cortex
Clin. Neurophysiol.
Transcranial direct current stimulation: state of the art 2008
Brain Stimul.
The assessment and analysis of handedness: the Edinburgh inventory
Neuropsychologia
LORETA imaging of P300 in schizophrenia with individual MRI and 128-channel EEG
Neuroimage
Skin lesions after treatment with transcranial direct current stimulation (tDCS)
Brain Stimul.
Low resolution electromagnetic tomography: a new method for localizing electrical activity in the brain
Int. J. Psychophysiol.
Updating P300: an integrative theory of P3a and P3b
Clin. Neurophysiol.
Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients
Brain Res. Bull.
Regional activation of the human medial temporal lobe during intentional encoding of objects and positions
Neuroimage
Transcranial direct stimulation and fluoxetine for the treatment of depression
Eur. Psychiatry
Prefrontal phase locking to hippocampal theta oscillations
Neuron
Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients
Biol. Psychiatry
The role of the nucleus accumbens and rostral anterior cingulate cortex in anhedonia: integration of resting EEG, fMRI, and volumetric techniques
Neuroimage
Recharging cognition with DC brain polarization
Trends Cogn. Sci.
Source localization of mesial temporal interictal epileptiform discharges: correlation with intracranial foramen ovale electrode recordings
Clin. Neurophysiol.
Depth electrode recorded cerebral responses with deep brain stimulation of the anterior thalamus for epilepsy
Clin. Neurophysiol.
Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain
J. Physiol.
Regional modulation of BOLD MRI responses to human sensorimotor activation by transcranial direct current stimulation
Magn. Reson. Med.
Modulating presence and impulsiveness by external stimulation of the brain
Behav. Brain Funct.
Brain stimulation modulates driving behavior
Behav. Brain Funct.
Single-trial analysis of oddball event-related potentials in simultaneous EEG-fMRI
Hum. Brain Mapp.
A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression
Int. J. Neuropsychopharmacol.
Modulatory effects of anodal transcranial direct current stimulation on perception and pain thresholds in healthy volunteers
Eur. J. Neurol.
Physiological characteristics of capacity constraints in working memory as revealed by functional MRI
Cereb. Cortex
Anodal transcranial direct current stimulation of the prefrontal cortex enhances complex verbal associative thought
J. Cogn. Neurosci.
rTMS of the left dorsolateral prefrontal cortex modulates dopamine release in the ipsilateral anterior cingulate cortex and orbitofrontal cortex
PLoS ONE
Cited by (0)
- 1
Both authors contributed equally to the manuscript.