Rostral anterior cingulate cortex theta current density and response to antidepressants and placebo in major depression

Abstract

Objective To assess whether pretreatment theta current density in the rostral anterior cingulate (rACC) and medial orbitofrontal cortex (mOFC) differentiates responders from non-responders to antidepressant medication or placebo in a double-blinded study. Methods Pretreatment EEGs were collected from 72 subjects with Major Depressive Disorder (MDD) who participated in one of three placebo-controlled trials. Subjects were randomized to receive treatment with fluoxetine, venlafaxine, or placebo. Low-resolution brain electromagnetic tomography (LORETA) was used to assess theta current density in the rACC and mOFC. Results Medication responders showed elevated rACC and mOFC theta current density compared to medication non-responders (rACC: p=0.042; mOFC: p=0.039). There was no significant difference in either brain region between placebo responders and placebo non-responders. Conclusions Theta current density in the rACC and mOFC may be useful as a biomarker for prediction of response to antidepressant medication. Significance This is the first double-blinded treatment study to examine pretreatment rACC and mOFC theta current density in relation to antidepressant response and placebo response. Results support the potential clinical utility of this approach for predicting clinical outcome to antidepressant treatments in MDD.

Personalized Medicine: Review and Perspectives of Promising Baseline EEG Biomarkers in Major Depressive Disorder and Attention Deficit Hyperactivity Disorder

“…This suggests these two types of theta activity could have different implications and different origins. In line with Spronk et al [109], several studies have indeed shown low theta activity localized to the ACC, as estimated by source localization techniques, to respond worse to various antidepressant treatments [110,111,112,113]. These findings are in line with positron emission tomography and functional magnetic resonance imaging studies demonstrating low metabolic activity in the ACC is associated with worse treatment outcome; see also Pizzagalli [114] for an excellent review and meta-analysis on the rostral ACC (rACC) and treatment outcome.…”

Rostral anterior cingulate activity generates posterior versus anterior theta activity linked to agentic extraversion

“…More specifically, the major depression symptom of anhedonia, characterized by reward-insensitive behavior and blunted positive emotionality -and hence, apparently, the extremely low end of aE (Depue, 1995) -has been associated with abnormally low levels of activity in the ventral-rostral ACC (rACC) regions (Pizzagalli, Peccoralo, Davidson, & Cohen, 2006) and with blunted nucleus accumbens responses to reward signals (Wacker, Dillon, & Pizzagalli, 2009). Furthermore, pharmacological challenge studies have demonstrated that the ACC responds to dopaminergic drugs (e.g., Völlm et al, 2004), and ACC activity also qualifies as a predictor for psychopharmacological treatment responses (for selective norepinephrine and serotonin reuptake inhibitors, see Korb, Hunter, Cook, & Leuchter, 2009).…”

Electrophysiological predictors of clinical response to antidepressants

“…Responders had greater pretreatment theta activity (6.5-8 Hz), again localized by LORETA to the rACC when compared to nonresponders and there was a significant correlation of pretreatment theta and improvement in depression after treatment, which replicates the findings of Pizzagalli et al (2001). In the first double-blind, placebo controlled study to examine the relationship of pretreatment EEG and antidepressant response, Korb et al (2009) used LORETA to localize theta activity (4-7 Hz) to the same rACC region as specified by Pizzagalli et al (2001). Patients who responded to either fluoxetine or venlafaxine (n=22) had greater theta than nonresponders (n=15), whereas there was no difference between placebo responders (n=15) and nonresponders.…”