Error-related Brain Activity as a Treatment Moderator and Index of Symptom Change during Cognitive-Behavioral Therapy or Selective Serotonin Reuptake Inhibitors

Abstract

Increased neural error monitoring, as measured by the error-related negativity (ERN), is a transdiagnostic neurobiological marker of anxiety. To date, little is known about whether the ERN can inform the choice between first-line anxiety disorder treatments and whether the ERN changes following treatment completion. The aim of the study was to therefore assess whether the ERN is a treatment moderator and index of symptom change during cognitive-behavioral therapy (CBT) or selective serotonin reuptake inhibitors (SSRIs). Participants included adult volunteers (M age=25.8±8.5; 67% female) with principal anxiety disorders (n=60) or no lifetime history of Axis I psychopathology (ie, healthy controls; n=26). A flanker task was used to elicit the ERN at baseline and 12 weeks later, following either CBT or SSRIs in the patient sample. Results indicated that baseline ERN was a significant treatment moderator such that a more enhanced baseline ERN was associated with greater reduction in anxiety symptoms within individuals who received CBT but not SSRIs. Results also revealed that the ERN increased pre- to post-treatment among patients randomized to SSRIs, but remained stable among patients randomized to CBT and healthy controls. Together, these novel findings highlight that ERN may help guide treatment decisions regarding engagement in CBT or SSRIs, especially among individuals with an enhanced ERN. The findings also suggest that SSRIs have the capacity to alter individual differences in the ERN, providing evidence that the ERN is not entirely static in patients with anxiety disorders.

Impact of pubertal timing and depression on error‐related brain activity in anxious youth

“…On the other hand, these findings are consistent with evidence suggesting that the ERN is a trait-like marker of anxiety, based on evidence that the ERN does not change after successful treatment for instance, in OCD (Hajcak et al, 2008; Riesel, Endrass, Auerbach, & Kathmann, 2015), nor does it correlated with the degree of anxiety symptom change (e.g. (Kujawa, Weinberg, et al, 2016), but see (Gorka et al, 2018)), and can be present in unaffected first-degree relatives of patients with anxiety (Carrasco, Harbin, et al, 2013; Riesel, Endrass, Kaufmann, & Kathmann, 2011). Therefore, put together, future studies should utilize a depression comparison group to determine if this effect is specific to the co-occurrence of depression and anxiety or also seen in the absence of anxiety.…”

Treatment-related changes towards normalization of the abnormal external signal processing in panic disorder

“…However, despite this recent study, the evidence of further significant changes of abnormal electrophysiological responses is still insufficient, particularly regarding the early processing of internal and external stimuli. For example, in performance monitoring, no study has yet found any evidence of significant changes of the enhanced ERPs evoked by the analysis of internal signals in patients suffering from an internalizing psychological disorder [7][8][9][10][11].…”

“…According to the reinforcement-learning theory, the Ne/ERN reflects a dopaminergic signal, sent from subcortical to cortical brain regions, which calls for adjustments of inaccurate performances [19]. Starting from the evidence of abnormal processing of errors in internalizing psychopathologies, some recent studies have investigated whether short periods of treatment induce a normalization of the augmented amplitude of the Ne/ERN in patients [7][8][9][10][11]. Despite substantial reductions of the symptoms after psychotherapy, these studies reported no significant effect of treatment on the Ne/ERN amplitude.…”

Electrophysiology as a theoretical and methodological hub for the neural sciences

“…Both biomarker and mechanism differ from an endophenotype, which describes an intermediate expression of genetic risk, usually in psychiatric populations (Iacono, ; Insel & Cuthbert, ). Fortuitously, frontal midline theta and related ERP features appear to be viable neural mechanisms (Section 3.1), endophenotypes (Kang et al, ; Zlojutro et al, ), diagnostic tools (Figure c), and predictors of treatment response (Burkhouse et al, ; Gorka et al, ) for patient groups defined by frontal dysfunction. These signatures can be up‐ and downregulated with pharmacology (Jocham & Ullsperger, ) and transcranical electric current (Reinhart & Woodman, ; Reinhart, Zhu, Park, & Woodman, ), demonstrating causal control over this signal and downstream effects on network instantiation and behavior in humans.…”

“…Video recording is commonly embedded with the signal (white sphere with black circle at top). These features demonstrate that the infrastructure already exists to capitalize upon any novel taskbased assessment of an EEG feature that contributes to diagnosis or prognosis for neurological or psychiatric disease [Colour figure can be viewed at wileyonlinelibrary.com] | 9 of 13 CAVANAGH 2016; Gorka et al, 2018) for patient groups defined by frontal dysfunction. These signatures can be up-and downregulated with pharmacology (Jocham & Ullsperger, 2009) and transcranical electric current (Reinhart & Woodman, 2014;Reinhart, Zhu, Park, & Woodman, 2015), demonstrating causal control over this signal and downstream effects on network instantiation and behavior in humans.…”