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

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 (http:// clinicaltrials.gov/show/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 seedbased 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. K E Y W O R D S depression, functional connectivity, placebo responses, rostral ACC, sham iTBS, sham rTMS

Improved Functional Organization in Patients With Primary Insomnia After Individually-Targeted Transcranial Magnetic Stimulation

“…Third, not all PI patients showed great improvement after SAINT administration, the underlying mechanism should be further studied in the future. Fourth, we did not control the placebo effect, further study should set up a placebo-controlled stimulations ( Wu et al, 2020 ).…”

Baseline patterns of resting functional connectivity within posterior default-mode intranetwork associated with remission to antidepressants in major depressive disorder

“…On the other hand, clinically this could be extrapolated that MDD patients with an anomalously reduced functional connectivity from pDMN are less likely to benefit acutely from antidepressant medications as first-line treatments. Congruent with previous studies ( Broyd et al, 2009 , Hamilton et al, 2011 , Holtzheimer and Mayberg, 2011 ), Wu et al (2020 ) assumed that baseline hyperconnectivity within the DMN predicted larger responses and account for the maladaptive depressive rumination and the excessive self-focus processing. Chin et al noted that higher connectivity within the DMN predicted better antidepressant efficacy for Sertraline ( Chin et al, 2020 ), suggesting MDD patients are associated with impaired neuronal plasticity, while brain-derived neurotrophic factor (BDNF) could play a key role in the modulation of neuronal networks ( Lee and Kim, 2010 ).…”

Brain Mechanism of Acupuncture Treatment of Chronic Pain: An Individual-Level Positron Emission Tomography Study

“…In summary, our research is in line with the growing interest in multivariate neuroimaging features and machine-learning methods for therapeutic outcome prediction and the tailoring of personalized interventions ( 58 – 60 ). In recent years, machine-learning-based predictive models have been successfully applied in a variety of therapies, such as transcranial magnetic stimulation ( 61 ), electroconvulsive therapy ( 62 ), and vagus nerve stimulation ( 63 ). These studies are beginning to unlock the potential and value of machine learning in the clinical practice.…”