Frontal and rostral anterior cingulate (rACC) theta EEG in depression: Implications for treatment outcome?

Martijn Arns; Amit Etkin; Ulrich Hegerl; Leanne M. Williams; Charles DeBattista; Donna M. Palmer; Paul B. Fitzgerald; Anthony Harris; Roger deBeuss; Evian Gordon

doi:10.1016/j.euroneuro.2015.03.007

Frontal and rostral anterior cingulate (rACC) theta EEG in depression: Implications for treatment outcome?

Martijn Arns^*
, Amit Etkin
, Ulrich Hegerl
, Leanne M. Williams
, Charles DeBattista
, Donna M. Palmer
, Paul B. Fitzgerald
, Anthony Harris
, Roger deBeuss
, Evian Gordon

^*Corresponding author for this work

Research Institute Brainclinics
Veterans Affairs Palo Alto Healthcare System, and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, CA, USA
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA
Department of Psychiatry and Psychotherapy, University of Leipzig, Germany
Brain Resource Ltd, Sydney, NSW, Australia
Brain Resource Ltd, San Francisco, CA, USA
Brain Dynamics Center, Westmead Millennium Institute for Medical Research and Sydney Medical School – Westmead, University of Sydney, Sydney, NSW, Australia
Monash Alfred Psychiatry Research Centre, Monash University Central Clinical School and the Alfred, Melbourne, VIC, Australia
Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, Australia
Department of Psychology, University of North Carolina at Asheville, Asheville, NC, USA

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression (HRSD₁₇). The resting-state EEG was assessed at baseline with eyes closed and source localization (eLORETA) was employed to extract theta from the rACC and frontal cortex. Patients with MDD had elevated theta in both frontal cortex and rACC, with small effect sizes. High frontal and rACC theta were associated with treatment non-response, but not with non-remission, and this effect was most pronounced in a subgroup with previous treatment failures. Low theta in frontal cortex and rACC are found in responders to antidepressant treatments with a small effect size. Future studies should investigate in more detail the role of previous treatment (failure) in the association between theta and treatment outcome.

Original language	English
Pages (from-to)	1190-1200
Number of pages	11
Journal	European Neuropsychopharmacology
Volume	25
Issue number	8
DOIs	https://doi.org/10.1016/j.euroneuro.2015.03.007
Publication status	Published - 1 Aug 2015

Funding

MA reports research grants and options from Brain Resource Ltd. (Sydney, Australia), acted as a paid consultant for the United BioSource Corporation (UBC), Bracket and Vivatech and is a co-inventor on 3 patent applications (A61B5/0402; US2007/0299323, A1; WO2010/139361 A1) related to EEG, neuromodulation and psychophysiology, but does not own these nor receives any proceeds related to these patents. AE reports research funds from Brain Resource Ltd. related to this study; UH was an advisory board member for Lilly, Lundbeck, Takeda Pharmaceuticals, Servier and Otsuka Pharma; a consultant for Nycomed; and a speaker for Bristol-Myers Squibb, Medice Arzneimittel, Novartis and Roche Pharma in the last 3 years; CD has received support from Brain Resource, CNS response, St. Jude, Astra Zeneca, Takeda, Assurex and is a consultant for Pfizer and Genentech; DMP has received income and stock options with the role of science and data processing manager as an employee with Brain Resource Ltd. AH has received consultancy fees from Janssen Australia and Lundbeck Australia. He has received payments for educational sessions run for Janssen Australia and the Lundbeck Institute. He has recently been an investigator on industry-sponsored trials by Hoffman-La Roche, Janssen-Cilag Australia and Brain Resource Ltd. RD has received research grants from Brain Resource Ltd.; EG is founder and receives income as Chief Executive Officer and Chairman for Brain Resource Ltd. He has stock options in Brain Resource Ltd. PBF is supported by a NHMRC Practitioner Fellowship (606907). PBF has received equipment for research from MagVenture A/S, Medtronic Ltd., Cervel Neurotech and Brainsway Ltd. and funding for research from Cervel Neurotech. We acknowledge the iSPOT-D Investigators Group, the contributions of iSPOT-D principal investigators at each site and the central management team (global coordinator Claire Day) and Chris Spooner for support in the data-analyses. Furthermore, we want to acknowledge earlier comments and suggestions from Diego Pizzagalli. This study was funded by the Brain Resource Company Operations Ltd . The clinical trials registration identifier is NCT00693849 . Data-analyses and writing of this manuscript were unconstrained and no financial support was involved in the data-analyses and writing of this manuscript.

Keywords

Anterior cingulate
Depression
EEG
LORETA
QEEG
Theta

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.euroneuro.2015.03.007

1-s2.0-S0924977X1500084X-mainFinal published version, 2.9 MBLicence: Taverne

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title = "Frontal and rostral anterior cingulate (rACC) theta EEG in depression: Implications for treatment outcome?",

abstract = "In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed and source localization (eLORETA) was employed to extract theta from the rACC and frontal cortex. Patients with MDD had elevated theta in both frontal cortex and rACC, with small effect sizes. High frontal and rACC theta were associated with treatment non-response, but not with non-remission, and this effect was most pronounced in a subgroup with previous treatment failures. Low theta in frontal cortex and rACC are found in responders to antidepressant treatments with a small effect size. Future studies should investigate in more detail the role of previous treatment (failure) in the association between theta and treatment outcome.",

keywords = "Anterior cingulate, Depression, EEG, LORETA, QEEG, Theta",

author = "Martijn Arns and Amit Etkin and Ulrich Hegerl and Williams, \{Leanne M.\} and Charles DeBattista and Palmer, \{Donna M.\} and Fitzgerald, \{Paul B.\} and Anthony Harris and Roger deBeuss and Evian Gordon",

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T2 - Implications for treatment outcome?

AU - Arns, Martijn

AU - Etkin, Amit

AU - Hegerl, Ulrich

AU - Williams, Leanne M.

AU - DeBattista, Charles

AU - Palmer, Donna M.

AU - Fitzgerald, Paul B.

AU - Harris, Anthony

AU - deBeuss, Roger

AU - Gordon, Evian

PY - 2015/8/1

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N2 - In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed and source localization (eLORETA) was employed to extract theta from the rACC and frontal cortex. Patients with MDD had elevated theta in both frontal cortex and rACC, with small effect sizes. High frontal and rACC theta were associated with treatment non-response, but not with non-remission, and this effect was most pronounced in a subgroup with previous treatment failures. Low theta in frontal cortex and rACC are found in responders to antidepressant treatments with a small effect size. Future studies should investigate in more detail the role of previous treatment (failure) in the association between theta and treatment outcome.

AB - In major depressive disorder (MDD), elevated theta current density in the rostral anterior cingulate (rACC), as estimated by source localization of scalp-recorded electroencenphalogram (EEG), has been associated with response to antidepressant treatments, whereas elevated frontal theta has been linked to non-response. This study used source localization to attempt to integrate these apparently opposite results and test, whether antidepressant response is associated with elevated rACC theta and non-response with elevated frontal theta and whether theta activity is a differential predictor of response to different types of commonly used antidepressants. In the international Study to Predict Optimized Treatment in Depression (iSPOT-D), a multi-center, international, randomized, prospective practical trial, 1008 MDD participants were randomized to escitalopram, sertraline or venlafaxine-XR. The study also recruited 336 healthy controls. Treatment response and remission were established after eight weeks using the 17-item Hamilton Rating Scale for Depression (HRSD17). The resting-state EEG was assessed at baseline with eyes closed and source localization (eLORETA) was employed to extract theta from the rACC and frontal cortex. Patients with MDD had elevated theta in both frontal cortex and rACC, with small effect sizes. High frontal and rACC theta were associated with treatment non-response, but not with non-remission, and this effect was most pronounced in a subgroup with previous treatment failures. Low theta in frontal cortex and rACC are found in responders to antidepressant treatments with a small effect size. Future studies should investigate in more detail the role of previous treatment (failure) in the association between theta and treatment outcome.

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KW - Depression

KW - EEG

KW - LORETA

KW - QEEG

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SN - 0924-977X

VL - 25

SP - 1190

EP - 1200

JO - European Neuropsychopharmacology

JF - European Neuropsychopharmacology

IS - 8

ER -

Frontal and rostral anterior cingulate (rACC) theta EEG in depression: Implications for treatment outcome?

Abstract

Funding

Keywords

UN SDGs

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