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.
Highlights
Depression is a major public health problem, affecting up to 20% of the US population at least once in their lifetime.[1]
Several studies utilizing positron emission tomography (PET) to measure regional glucose metabolism have suggested that Electroconvulsive therapy (ECT) reduces prefrontal activity,[10,11,12,13,14,15,16] but these results have not been consistently replicated.[17,18,19]
Whole brain voxel-wise analysis revealed a significant change in fractional amplitude of low frequency fluctuation (fALFF) from pre- to post-treatment time points (TP) in the subcallosal cingulate cortex (SCC) (Figure 2a)
Summary
Depression is a major public health problem, affecting up to 20% of the US population at least once in their lifetime.[1]. Identification of the neural circuitry associated with the efficacy of ECT may provide data needed to detect the CNS targets of effective antidepressant treatment, and be important for the development of new interventions with similar efficacy but reduced side effects.[8] To date, neuroimaging studies have failed to unambiguously identify functional changes in the brain that correspond to the therapeutic effects of ECT.[9] Several studies utilizing positron emission tomography (PET) to measure regional glucose metabolism have suggested that ECT reduces prefrontal activity,[10,11,12,13,14,15,16] but these results have not been consistently replicated.[17,18,19] The interpretation of these studies is limited by the relatively poor temporal resolution of this technique, as well as (in some instances) the relatively gross spatial resolution of the available scanners. Studies of regional cerebral blood flow, using PET or single-photon emission computed tomography (SPECT), have been even more variable (reviewed by Abbott et al.),[20] with no consistently replicated treatment targets identified
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