The ISAD (Infraslow Neurofeedback for Anxiety and Depression) Study: A Protocol for a Trans-Diagnostic, Randomized, Double-Blind, Sham-Controlled, Dose-Response, Parallel-Group Trial

Abstract

Background: The core intrinsic connectivity networks (ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individual’s with internalizing disorders (IDs; e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localised electroencephalogram neurofeedback (EEG-NFB) therapy targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a transdiagnostic, randomized, double-blind, sham-controlled, dose-response, parallel-group trial of standardized low-resolution electromagnetic tomography electrophysiological infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA eISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary aim will be to assess the clinical efficacy of sLORETA eISF-NFB via relevant patient-reported outcomes (PROs). Methods: We will randomly assign participants with a current diagnosis of MDD, GAD, and/or SOC to one of four groups: 1) 12 sessions of posterior cingulate cortex (PCC) up-training (n=15), 2) 6 sessions of yoked-sham training followed by 6 sessions of PCC up-training (n=15), 3) 12 sessions of concurrent mid-cingulate (MCC) down-training and PCC up-training (n=15), or 4) 6 sessions of yoked-sham training followed by 6 sessions of concurrent MCC down-training and PCC up-training. Transdiagnostic PROs, as well as resting-state neuro-physiological measures (EEG; electrocardiography, ECG; electrodermal activity, EDA), will be collected from all subjects at baseline, mid-training, 1 week post-training, and 1 month post-training. We will further compare baseline PROs and neuro-physiological measures to age- and sex-matched non-ID (i.e. no ID diagnosis) controls. Discussion: This protocol will outline the rationale and research methodology for a clinical trial of sLORETA eISF-NFB targeting key nodes within the core ICNs in a population with IDs with the primary aim being to assess its specific (e.g. non-placebo induced) efficacy via PROs. Trial Registration: Our study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial Id: ACTRN12619001428156)

Is There a Difference in EEG Characteristics in Acute, Chronic, and Experimentally Induced Musculoskeletal Pain States? a Systematic Review

“…In such cases, future studies can refer to existing divisions used for neuromodulatory approaches utilizing slow and infraslow oscillations for various conditions. [102][103][104][105] Surprisingly, an important observation is that none of the included studies has evaluated a full band EEG in the studied population. A growing body of literature is available indicating the important role of frequency bands below 1 Hz (slow and infraslow bands) in pain processing and modulation.…”