Subgenual cingulate cortical activity predicts the efficacy of electroconvulsive therapy

Abstract

Electroconvulsive therapy (ECT) is the most effective treatment for depression, yet its mechanism of action is unknown. Our goal was to investigate the neurobiological underpinnings of ECT response using longitudinally collected resting-state functional magnetic resonance imaging (rs-fMRI) in 16 patients with treatment-resistant depression and 10 healthy controls. Patients received bifrontal ECT 3 times a week under general anesthesia. We acquired rs-fMRI at three time points: at baseline, after the 1st ECT administration and after the course of the ECT treatment; depression was assessed with the Hamilton Depression Rating Scale (HAM-D). The primary measure derived from rs-fMRI was fractional amplitude of low frequency fluctuation (fALFF), which provides an unbiased voxel-wise estimation of brain activity. We also conducted seed-based functional connectivity analysis based on our primary findings. We compared treatment-related changes in HAM-D scores with pre- and post-treatment fALFF and connectivity measures. Subcallosal cingulate cortex (SCC) demonstrated higher BOLD signal fluctuations (fALFF) at baseline in depressed patients, and SCC fALFF decreased over the course of treatment. The baseline level of fALFF of SCC predicted response to ECT. In addition, connectivity of SCC with bilateral hippocampus, bilateral temporal pole, and ventromedial prefrontal cortex was significantly reduced over the course of treatment. These results suggest that the antidepressant effect of ECT may be mediated by downregulation of SCC activity and connectivity. SCC function may serve as an important biomarker of target engagement in the development of novel therapies for depression that is resistant to treatment with standard medications.

Figure 1

Study design. Patients underwent a course of bifrontal ECT (3 times per week) and were scanned 3 time points during treatment. They were scanned at baseline, within 36 h after the first ECT treatment and within 36 h after the last treatment. The last ECT treatment was obtained at remission or achieved after the 8th ECT treatment if the patient had not remitted (ECT course might have continued for clinical reasons). ECT, electroconvulsive therapy; TP, time point.

Figure 2

Decreases in fALFF between TP1 to TP3. (a) Voxel-based statistics across whole brain. (b) Post hoc analysis of the primary result including all the three time points from both patients and healthy controls (with blue). These results show that fALFF was higher at baseline in depressed patients, and it was normalized during the course of ECT (see statistics in the text). ECT, electroconvulsive therapy; fALFF, fractional amplitude of low frequency fluctuation; TP, time point.

Figure 3

Functional connectivity of subcallosal cingulate cortex (SCC, the most significant region of the fALFF analysis) was used as a seed region to evaluate functional connectivity. Between TP1 and TP3, there were significant decreases in the correlation in three regions: ventromedial prefrontal cortex (vmPFC), bilateral parahippocampal gyrus (HCampus) and bilateral temporal pole (TempPole). We also detected increased correlations in the right supramarginal gyrus (Table 1b). Blue box plots represent normal values measured on the respective areas and time points. ECT, electroconvulsive therapy; fALFF, fractional amplitude of low frequency fluctuation; TP, time point.