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

Eur Neuropsychopharmacol. 2015 Aug;25(8):1190-200. doi: 10.1016/j.euroneuro.2015.03.007. Epub 2015 Apr 20.


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.

Publication types

  • Clinical Trial, Phase IV
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Brain Mapping
  • Citalopram / therapeutic use
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology
  • Electroencephalography
  • Female
  • Frontal Lobe / drug effects*
  • Frontal Lobe / physiopathology
  • Gyrus Cinguli / drug effects*
  • Gyrus Cinguli / physiopathology
  • Humans
  • Male
  • Prospective Studies
  • Psychiatric Status Rating Scales
  • Remission Induction
  • Sertraline / therapeutic use
  • Severity of Illness Index
  • Theta Rhythm / drug effects*
  • Venlafaxine Hydrochloride / therapeutic use


  • Antidepressive Agents
  • Citalopram
  • Venlafaxine Hydrochloride
  • Sertraline