Elsevier

NeuroImage

Volume 87, 15 February 2014, Pages 332-344
NeuroImage

A computational modelling study of transcranial direct current stimulation montages used in depression

https://doi.org/10.1016/j.neuroimage.2013.11.015Get rights and content

Highlights

  • First computational study to analyse various tDCS depression montages.

  • Compare tDCS depression montages in different realistic head models.

  • Sensitivity analyses on effects of electrodes were conducted on selected montages.

  • Anodal stimulation on F3 normally produced high E-field strength in the left DLPFC.

  • An extracephalic electrode resulted in a more widespread current distribution.

Abstract

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild electric current to the brain through electrodes placed on the scalp. Several clinical studies suggest that tDCS may have clinically meaningful efficacy in the treatment of depression. The objective of this study was to simulate and compare the effects of several tDCS montages either used in clinical trials or proposed, for the treatment of depression, in different high-resolution anatomically-accurate head models. Detailed segmented finite element head models of two subjects were presented, and a total of eleven tDCS electrode montages were simulated. Sensitivity analysis on the effects of changing the size of the anode, rotating both electrodes and displacing the anode was also conducted on selected montages. The F3–F8 and F3–F4 montages have been used in clinical trials reporting significant antidepressant effects and both result in relatively high electric fields in dorsolateral prefrontal cortices. Other montages using a fronto-extracephalic or fronto-occipital approach result in greater stimulation of central structures (e.g. anterior cingulate cortex) which may be advantageous in treating depression, but their efficacy has yet to be tested in randomised controlled trials. Results from sensitivity analysis suggest that electrode position and size may be adjusted slightly to accommodate other priorities, such as skin discomfort and damage.

Introduction

Transcranial direct current stimulation (tDCS) is a neuromodulatory technique which involves passing a mild electric current to the brain through electrodes placed on the scalp. This direct constant flow of current modulates underlying cortical activity with specific outcomes related to anodal or cathodal stimulation (Nitsche and Paulus, 2000, Nitsche and Paulus, 2001). The relative position (electrode montage) and size of the anode and cathode determine the distribution of current density throughout the brain (Bikson et al., 2010, Datta et al., 2011, Lee et al., 2012, Miranda et al., 2009, Wagner et al., 2007). Thus there is potential for stimulation to be focussed on specific cortical brain regions for therapeutic or investigative purposes or more diffuse effects can be produced if widespread activation of brain regions is desired.

A key application of tDCS has been investigated in the treatment of depression. Several recent open label and placebo-controlled trials, and a meta-analysis of mean change in depression scores from placebo-controlled studies suggest that tDCS may have clinically meaningful efficacy (Boggio et al., 2008, Brunoni et al., 2011, Fregni et al., 2006a, Fregni et al., 2006b, Kalu et al., 2012, Loo et al., 2012, Martin et al., 2011, Palm et al., 2011). These studies focused on anodal stimulation of the left dorsolateral prefrontal cortex (DLPFC), based on observations that this area has been associated with underactivity in depression (Grimm et al., 2008). However, studies differed in the location of the cathode, i.e. the return electrode — right supraorbital, right lateral orbitofrontal, right DLPFC or in an extracephalic position. Though the anodal left DLPFC electrode is often considered the “active” electrode, the placement of the cathode is important for several reasons: shunting of much of the current over the scalp may occur if the inter-electrode distance is too close (Datta et al., 2008, Miranda et al., 2006, Weaver et al., 1976), current density under the anode is affected by the placement of the reference or “return” electrode (Bikson et al., 2010, Datta et al., 2011), and the pattern of brain areas stimulated will be determined by the overall montage. All of these factors may have important therapeutic implications.

Pathophysiological changes in depression are system-wide, involving a network of various cortical and limbic structures rather than a solitary brain region such as the left DLPFC (Mayberg, 2007). Hypoactivity in cortical regions and hyperactivity in subcortical and limbic regions is often associated with symptoms of depression (Fitzgerald et al., 2008, Mayberg, 1997). Meta-analyses have identified frontal and temporal cortices, the insula and cerebellum as regions of hypoactivity while subcortical and limbic regions tend to be hyperactive. This distributed network of structures includes the DLPFC, medial prefrontal cortex (MPFC), orbitofrontal cortex (OFC), as well as the anterior cingulate cortex (ACC), insula and hippocampus (Fox et al., 2012, Mayberg, 2003). Most recently, functional connectivity studies have suggested altered activity at a network level during the resting state (Carballedo et al., 2011). In particular, there is increased functional connectivity in the subgenual anterior cingulate (sgACC), thalamus and OFC in people with depression (Greicius et al., 2007). Further, overactivity in the sgACC has been shown to be strongly negatively correlated with resting state underactivity in the left DLPFC (Fox et al., 2012).

Studies of deep brain stimulation (DBS) in depression have also provided insight into the critical regions involved in depression. Consistent with imaging studies, DBS interventions targeted at the sgACC have demonstrated efficacy in reducing symptoms of depression (Lozano et al., 2012, Mayberg et al., 2005). DBS to specific regions of the basal ganglia such as the nucleus accumbens (NAcc) and the ventral capsule/ventral striatum (VC/VS) have also been found to have significant antidepressant effects (Anderson et al., 2012, Bewernick et al., 2010, Bewernick et al., 2012, Malone et al., 2009).

As the therapeutic potential of tDCS in psychiatric disorders is further explored, information on how different electrode arrangements determine current density in key brain regions, is essential. This study compared the effects of several DCS montages, with realistic head models reconstructed from MRI head scans, by investigating the brain electric field (E-field) distribution and the average E-field in various brain regions. tDCS montages modelled were those used in recent tDCS depression studies: the F3–supraorbital (F3–SO) montage first used when interest was rekindled in tDCS from 2006 onwards (Boggio et al., 2008, Fregni et al., 2006a, Fregni et al., 2006b, Loo et al., 2010, Palm et al., 2011), and modified approaches in which the cathode was moved more laterally to reduce shunting, F3–F8 (Loo et al., 2012), to the right DLPFC, F3–F4 (Brunoni et al., 2011, Brunoni et al., 2013, Dell'Osso et al., 2012, Ferrucci et al., 2009a, Ferrucci et al., 2009b), or to an extracephalic position to achieve a more widespread pattern of brain activation, F3–extracephalic (F3–EC, brain sites based on the 10–20 EEG system; Martin et al., 2011). The bilateral supraorbital–extracephalic (SO–EC) montage most commonly used in earlier, pre-2000 studies, involving two small anodes at the frontal poles and an extracephalic cathode was also modelled (Arul-Anandam and Loo, 2009, Lippold and Redfearn, 1964, Redfearn et al., 1964). In addition, several hypothetical montages were modelled: supraorbital–occipital (SO–OCC), premised on maximal stimulation of the sgACC and other central and midline subcortical structures; temporal–extracephalic (TMP–EC), prioritising temporal lobe stimulation as neurotrophic changes in this region may have a key role in the pathophysiology of depression (Pittenger and Duman, 2007), and supraorbital–cerebellum (SO–CB), as abnormal cerebellar modulation of the cerebello-thalamo-cortical pathway has been implicated in the mood and cognitive symptoms associated with several psychiatric disorders, including bipolar disorder and depression (Hoppenbrouwers et al., 2008).

The montages were modelled in two subjects — one male and one female — to examine the extent to which inter-individual differences in head anatomy affect variation in electric field with different montages. Finally, a sensitivity analysis was performed to examine the effects of displacing the anodal electrode by ~ 1 cm, to inform on the likely importance of accuracy in electrode placement in clinical applications.

Section snippets

Image segmentation and mesh generation

Two different high-resolution computational head models were reconstructed from human subjects. One subject was a 35-year-old Asian male whose MRI head scan, labelled “Msub” (short for male subject), was truncated at the level of cervical vertebra 6. The other was a 42-year-old Caucasian female, labelled “Fsub” (female subject, Fig. 1S in Supplementary data): her scan was truncated at the level of the atlas-axis, i.e., cervical vertebrae 1–2. T1-weighted MRI scans of both subjects were obtained

Results

Fig. 4 shows the E-field magnitude and direction on the cortical surface of the brain for six selected tDCS electrode montages with Msub-aniso. Fig. 5 shows the E-field profile with the same head model in cross-sectional slices of the brain for the selected tDCS electrode montages. The montages which utilised the F3 anode and a contralateral frontal cephalic cathode (F3–SO, F3–F8, F3–F4-1 as shown in Fig. 4) exhibited higher current density predominately in the frontal lobes of the brain. F3–F8

Clinical implications of electrode montages

A number of recent tDCS studies have reported positive antidepressant effects in depressed patients (Boggio et al., 2008, Brunoni et al., 2011, Brunoni et al., 2013, Fregni et al., 2006a, Fregni et al., 2006b, Kalu et al., 2012, Loo et al., 2012, Martin et al., 2011, Palm et al., 2011). The rationale guiding the choice of electrode montage in these trials is up-regulation of the left DLPFC, with the anode placed on F3 (Boggio et al., 2008, Brunoni et al., 2011, Brunoni et al., 2013, Dell'Osso

Conclusion

With the aid of computational modelling, this study presented a systematic analysis of various tDCS electrode montages that have been used in clinical trials, as well as hypothetical montages specifically for the treatment of depression. The overall profile of E-field magnitude and direction, as well as the average E-field magnitudes in key brain regions were presented. While the clinical significance of these outcomes is not as yet well understood, these results may form a useful reference for

Acknowledgment

The authors would like to thank Prof. Caroline Rae and Dr. John Geng from Neuroscience Research Australia for their support in acquiring and processing the structural MRI and DT-MRI data, Dr. Elizabeth Tancred from the University of New South Wales for her expertise in the head anatomy, and Dr. Angelo Alonzo from the Black Dog Institute for his help in determining the accurate position of scalp electrodes.

References (73)

  • B. Dell'Osso et al.

    Transcranial direct current stimulation for the outpatient treatment of poor-responder depressed patients

    Eur. Psychiatry

    (2012)
  • R. Ferrucci et al.

    Transcranial direct current stimulation in severe, drug-resistant major depression

    J. Affect. Disord.

    (2009)
  • M. Fox et al.

    Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate

    Biol. Psychiatry

    (2012)
  • M. Greicius et al.

    Resting-state functional connectivity in major depression: abnormally increased contributions from subgenual cingulate cortex and thalamus

    Biol. Psychiatry

    (2007)
  • S. Grimm et al.

    Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: an fMRI study in severe major depressive disorder

    Biol. Psychiatry

    (2008)
  • S. Hoppenbrouwers et al.

    The role of the cerebellum in the pathophysiology and treatment of neuropsychiatric disorders: a review

    Brain Res. Rev.

    (2008)
  • Y. Lai et al.

    Estimation of in vivo human brain-to-skull conductivity ratio from simultaneous extra- and intra-cranial electrical potential recordings

    Clin. Neurophysiol.

    (2005)
  • W. Lee et al.

    Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: influence of white matter anisotropic conductivity

    NeuroImage

    (2012)
  • D. Malone et al.

    Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression

    Biol. Psychiatry

    (2009)
  • D. Martin et al.

    Fronto-extracephalic transcranial direct current stimulation as a treatment for major depression: an open-label pilot study

    J. Affect. Disord.

    (2011)
  • H. Mayberg

    Defining the neural circuitry of depression: toward a new nosology with therapeutic implications

    Biol. Psychiatry

    (2007)
  • H. Mayberg et al.

    Deep brain stimulation for treatment-resistant depression

    Neuron

    (2005)
  • M. Mendonca et al.

    Transcranial dc stimulation in fibromyalgia: optimized cortical target supported by high-resolution computational models

    J. Pain

    (2011)
  • P. Miranda et al.

    Modeling the current distribution during transcranial direct current stimulation

    Clin. Neurophysiol.

    (2006)
  • P. Miranda et al.

    What does the ratio of injected current to electrode area tell us about current density in the brain during tDCS?

    Clin. Neurophysiol.

    (2009)
  • V. Moliadze et al.

    Electrode-distance dependent after-effects of transcranial direct and random noise stimulation with extracephalic reference electrodes

    Clin. Neurophysiol.

    (2010)
  • P. Nicholson

    Specific impedance of cerebral white matter

    Exp. Neurol.

    (1965)
  • S. Shahid et al.

    Numerical investigation of white matter anisotropic conductivity in defining current distribution under tDCS

    Comput. Methods Programs Biomed.

    (2013)
  • D. Shattuck et al.

    BrainSuite: an automated cortical surface identification tool

    Med. Image Anal.

    (2002)
  • T. Wagner et al.

    Transcranial direct current stimulation: a computer-based human model study

    NeuroImage

    (2007)
  • C. Wolters et al.

    Influence of tissue conductivity anisotropy on EEG/MEG field and return current computation in a realistic head model: a simulation and visualization study using high-resolution finite element modeling

    NeuroImage

    (2006)
  • M. Akhtari et al.

    Conductivities of three-layer human skull

    Brain Topogr.

    (2000)
  • M. Akhtari et al.

    Conductivities of three-layer live human skull

    Brain Topogr.

    (2002)
  • S. Bai et al.

    A review of computational models of transcranial electrical stimulation

    Crit. Rev. Biomed. Eng.

    (2013)
  • P. Basser et al.

    New currents in electrical stimulation of excitable tissues

    Annu. Rev. Biomed. Eng.

    (2000)
  • S. Baumann et al.

    The electrical conductivity of human cerebrospinal fluid at body temperature

    IEEE Trans. Biomed. Eng.

    (1997)
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