Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up

Abstract

Background and objective: Repetitive transcranial magnetic stimulation (rTMS) is a first-line treatment for treatment-resistant depression (TRD). The mechanisms of action of rTMS are not fully understood, and no biomarkers are available to assist in clinical practice to predict response to rTMS. This study aimed to demonstrate that after-rTMS clinical improvement is associated with functional connectivity (FC) changes of the subgenual cingulate cortex (sgACC) and rostral anterior cingulate (rACC), and FC of sgACC and rACC might serve as potential predictors for treatment response. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected within 1 week before rTMS initiation in 50 TRD patients to predict subsequent response to rTMS on the left dorsolateral prefrontal cortex (DLPFC). Follow-up rs-fMRI was obtained 12 weeks after completion of rTMS and neural correlates of rTMS in sgACC-and rACC-related FC patterns were compared to before rTMS data and with rs-fMRI from healthy participants. Results: Treatment response was associated with lower FC of sgACC to right DLPFC and higher FC of rACC to left lateral parietal cortex (IPL) measured at baseline. Using sgACC-DLPFC and rACC-IPL connectivity as features, responder-nonresponder classification accuracies of 84% and 76% (end-of-treatment), 88% and 81% (3-month follow-up), respectively were achieved. Longitudinal rs-fMRI data analyses revealed that the hyperconnectivity between sgACC and visual cortex was normalized to a level which was comparable to that of healthy participants. Conclusions: Brain activity patterns in depression are predictive of treatment response to rTMS, and longitudinal change of brain activity in relevant brain circuits after rTMS is associated with treatment response in depression. Target engagement paradigms may offer opportunities to increase the efficacy of rTMS in TRD by optimal selection of patients for treatment. Trial registration: ClinicalTrials.gov Identifiers: NCT01887782 and NCT02800226.

Parcel-guided rTMS for depression

“…The present results suggest a dysfunctional pattern associated with depression that can be modulated bidirectionally (top-down/bottom-up), depending upon the precise location of the rTMS target. The present study reinforces first that small shifts in target location within DLPFC may produce large differences in outcome, and that alterations in rsfc patterns may be helpful both in selection of subjects and monitoring of response 20,21 .…”

Functional connectivity between the amygdala and subgenual cingulate gyrus predicts the antidepressant effects of ketamine in patients with treatment‐resistant depression

“…10,[44][45][46] However, fewer studies have reported a relationship between changes in RSFC and treatment response heterogeneity in TRD patients. 18,47,48 In this study, the seed-based exploratory analysis at baseline revealed a cluster that was associated with treatment response to ketamine within the AN, but not the DMN. This suggests that the AN plays a key role in treatment response in TRD with respect to the DMN in treatment-sensitive depression (TSD).…”

Pregenual or subgenual anterior cingulate cortex as potential effective region for brain stimulation of depression

“…Albeit the results of many imaging studies support the sgACC as a critical region of MDD (Downey et al, 2016; Ho et al, 2014; Jaworska et al, 2014; Liu et al, 2015), including the FC findings of baseline sgACC‐DLPFC and sgACC‐left superior medial frontal gyrus connectivity predicted subsequent clinical improvement (Baeken et al, 2014; Cash et al, 2019; Fox et al, 2012; Ge, Downar, Blumberger, Daskalakis, & Vila‐Rodriguez, 2020; Liston et al, 2014; Weigand et al, 2018), there have a lot of evidences supporting the pgACC as a critical region of MDD (Ball, Stein, & Paulus, 2014; Boes et al, 2018; Pizzagalli, 2010; Silverstein et al, 2015; Zhou et al, 2017), and pgACC has been reported to show higher FC with the left lateral parietal cortex (IPL) at baseline in better clinical response group (Ge et al, 2020). In view of the above FC‐based researches, the current study investigated the ACC‐DLPFC FC as well as its association with rTMS efficacy.…”