Magnetoencephalographic Correlates of Emotional Processing in Major Depression Before and After Pharmacological Treatment

Abstract

Background:In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation.Methods:Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale.Results:Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy.Conclusions:The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.

The pulvinar nucleus and antidepressant treatment: dynamic modeling of antidepressant response and remission with ultra-high field functional MRI

“…MD patients exhibit a reduced visual arousal in the right TPJ [49]. Treatment elevated TPJhypoactivity towards activity levels of healthy controls [50]. These studies corroborate a role of the TPJ in enabling internal predictions about external sensory events [51], which might be altered in MD.…”

Motivated attention and family risk for depression: Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal blunted emotional responsivity

“…Consistent with previous findings in depressed patients (Domschke et al, 2015, Kayser et al, 2000, Kayser et al, 2001, Moratti et al, 2008, Zwanzger et al, 2016), particularly in those with a family history of depression (Moratti et al, 2015), we found that an early, emotion-specific right-lateralized activation of occipitotemporal cortex at around 200 ms post stimulus onset was less robust in high compared with low risk individuals. Even stronger reductions of these early emotional effects were observed for individuals with a lifetime history of MDD compared to those without; however, the present analysis indicated these effects were unrelated and not necessarily additive.…”

“…This could be due to a failure to allocate more attention to motivationally significant stimuli via re-entrant subcortical feedback of anterior brain regions to visual cortex (e.g., Keil et al, 2009, Keil et al, 2012, Moratti et al, 2011, Sabatinelli et al, 2007, Sabatinelli et al, 2013), or because of active, prefrontal top-down regulation of these posterior regions (Pessoa, 2008, Tang et al, 2015), or both. Either way, early onset and putative origin of these effects in right extrastriate cortex strongly suggests attentional modulation that preceded conscious awareness of motivationally salient stimuli (Domschke et al, 2015, LeDoux, 1989, LeDoux, 2015, Tamietto and de Gelder, 2010). Moreover, the spatial localization appears to complement previous reports of right temporoparietal cortical thinning and greater EEG alpha in individuals with parental depression (Bruder et al, 2005, Bruder et al, 2007, Bruder et al, 2012, Peterson et al, 2009).…”

“…Blunted electrophysiological responses involving right temporoparietal cortex to emotionally-arousing stimuli in MDD may even constitute a biomarker of treatment success. In a pre-/post-treatment design with 25 MDD patients receiving the serotonergic/noradrenergic antidepressant mirtazapine for four weeks, baseline hypoactivation of rTPJ and bilateral dorsolateral prefrontal cortex (dlPFC) during emotional picture presentation normalized with successful treatment (Domschke et al, 2015). These effects emerged as early as 150 ms after stimulus onset, suggesting dysfunctional processing (rTPJ) and top-down regulation (dlPFC) of emotional stimuli at a preconscious level.…”

Neuronal generator patterns at scalp elicited by lateralized aversive pictures reveal consecutive stages of motivated attention

“…Therefore, the negative arousal-related emotional ERP effects, which include an early right-greater-than-left asymmetry over occipitotemporal regions that is modulated by hemifield, may be rather universal. However, we and others have found marked reductions of emotional ERP modulations in clinically-depressed patients suggesting hypofunction of right temporoparietal regions (e.g., Foti et al, 2010; Kayser et al, 2000, 2001; Moratti et al, 2008), and recent electrophysiologic evidence indicates that blunted responses to emotionally-arousing stimuli in major depression may serve as a possible biomarker of treatment success (Domschke et al, 2015; Zwanzger et al, 2016). Moreover, similar electrophysiological deficits may even be present in individuals at high family risk for depression (Moratti et al, 2015), as found with a preliminary analysis for a subsample of this cohort (Kayser et al, 2014).…”