Baseline functional connectivity may predict placebo responses to accelerated rTMS treatment in major depression

Guo-Rong Wu, Xiaowan Wang, Chris Baeken, Guo-Rong Wu, Xiaowan Wang, Chris Baeken

Abstract

Although in theory sham repetitive transcranial magnetic stimulation (rTMS) has no inherent therapeutic value, nonetheless, such placebo stimulations may have relevant therapeutic effects in clinically depressed patients. On the other hand, antidepressant responses to sham rTMS are quite heterogeneous across individuals and its neural underpinnings have not been explored yet. The current brain imaging study aims to detect baseline neural fingerprints resulting in clinically beneficial placebo rTMS treatment responses. We collected resting-state functional magnetic resonance imaging data prior to a registered randomized clinical trial of accelerated placebo stimulation protocol in patients documented with treatment-resistant depression (https://ichgcp.net/clinical-trials-registry/NCT01832805). In addition to global brain connectivity and rostral anterior cingulate cortex (rACC) seed-based functional connectivity (FC), elastic-net regression and cross-validation procedures were used to identify baseline intrinsic brain connectivity biomarkers for sham-rTMS responses. Placebo responses to accelerated sham rTMS were correlated with baseline global brain connectivity in the rACC/ventral medial prefrontal cortex (vmPFC). Concerning the rACC seed-based FC analysis, the placebo response was associated positively with the precuneus/posterior cingulate (PCun/PCC) cortex and negatively with the middle frontal gyrus. Our findings provide first brain imaging evidence for placebo responses to sham stimulation being predictable from rACC rsFC profiles, especially in brain areas implicated in (re)appraisal and self-focus processes.

Keywords: depression; functional connectivity; placebo responses; rostral ACC; sham iTBS; sham rTMS.

Conflict of interest statement

The authors declare that they have no conflict of interest.

© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.

Figures

Figure 1
Figure 1
One‐sample t‐tests results of the baseline rACC seed‐based FC (p < .05, FWE correction at the cluster level with a voxel‐level threshold of p < .001 uncorrected). Two confound regression strategies were used: (a) aCompcor and (b) global signal regression
Figure 2
Figure 2
Pretreatment brain connectivity (aCompCor noise removal approach) prediction of the placebo response to sham aiTBS treatment. (a/b) Voxel weight values of multivariate elastic‐net regression, with cluster size >100 voxels; a: GBC, b: rACC seed‐based FC. (c) The predicted HDRS%change scores were significantly correlated with the actual scores (GBC: r = .486, p = .023; rACC seed‐based FC: r = .498, p = .018), with age, gender, and mean FD as the nuisance covariates

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