Hippocampal-subregion functional alterations associated with antidepressant effects and cognitive impairments of electroconvulsive therapy

Abstract

Background: Electroconvulsive therapy (ECT), an effective antidepressive treatment, is frequently accompanied by cognitive impairment (predominantly memory), usually transient and self-limited. The hippocampus is a key region involved in memory and emotion processing, and in particular, the anterior-posterior hippocampal subregions has been shown to be associated with emotion and memory. However, less is known about the relationship between hippocampal-subregion alterations following ECT and antidepressant effects or cognitive impairments.

Methods: Resting-state functional connectivity (RSFC) based on the seeds of hippocampal subregions were investigated in 45 pre- and post-ECT depressed patients. Structural connectivity between hippocampal subregions and corresponding functionally abnormal regions was also conducted using probabilistic tractography. Antidepressant effects and cognitive impairments were measured by the Hamilton Depressive Rating Scale (HDRS) and the Category Verbal Fluency Test (CVFT), respectively. Their relationships with hippocampal-subregions alterations were examined.

Results: After ECT, patients showed increased RSFC in the hippocampal emotional subregion (HIPe) with the left middle occipital gyrus (LMOG) and right medial temporal gyrus (RMTG). Decreased HDRS was associated with increased HIPe-RMTG RSFC (r = -0.316, p = 0.035) significantly and increased HIPe-LMOG RSFC at trend level (r = -0.283, p = 0.060). In contrast, the hippocampal cognitive subregion showed decreased RSFC with the bilateral angular gyrus, and was correlated with decreased CVFT (r = 0.418, p = 0.015 for left; r = 0.356, p = 0.042 for right). No significant changes were found in structural connectivity.

Conclusion: The hippocampal-subregions functional alterations may be specially associated with the antidepressant and cognitive effects of ECT.

Keywords: Depression; electroconvulsive therapy; fMRI; functional connectivity; hippocampal subregions.

Fig. 1.

Sagittal, coronal, and axial views displaying the ROI. (a) Hippocampal subregions were derived from a recent data-driven study that revealed a subspecialization in the hippocampus using coactivation-based parcellation. The left hippocampus was segmented into three subregions, the HIPe (blue), the HIPc, (red), and the HIPp (green). There were overlapping areas between HIPe and HIPc (the magenta area) and overlapping areas between HIPc and HIPp (yellow). (b) After excluding overlapping areas, the remaining regions HIPe (blue), HIPc (red) and HIPp (green), were used as ROI for further analysis. ROI, region of interest; HIPe, hippocampal emotional region; HIPc, hippocampal cognitive region; HIPp, hippocampal perceptual region. These ROIs was based on the public results from the work of Robinson et al. (2015) (http://anima.fz-juelich.de/).

Fig. 2.

The effect of ECT on RSFC of the HIPe and its relationship with clinical-symptom changes. (a) There was greater RSFC between the HIPe and the LMOG, left putamen and RMTG after ECT (Z > 3.1, p < 0.001, cluster-level FWE corrected). (b) There was a significant relationship between increased HIPe-LMOG connectivity and reduced HDRS at trend level. (c) There was a significant relationship between increased HIPe-RMTG connectivity and reduced HDRS (two-tailed, no correction). All scores were calculated using post-ECT scores subtracted from pre-ECT scores. ECT, electroconvulsive therapy; RSFC, resting-state functional connectivity; HIPe, hippocampal emotional region; LMOG, left middle occipital gyrus; RMTG, right medial temporal gyrus; FWE, family-wise error; HDRS, Hamilton Depressive Rating Scale.

Fig. 3.

The effect ECT RSFC of the HIPc and its relationship with memory change. (a) There was lower RSFC between the HIPc and both the LAG and right RAG after ECT. In contrast, there was increased RSFC between the left postcentral gyrus/inferior parietal lobule and the medial frontal gyrus (Z > 3.1, p < 0.001, cluster-level FWE corrected). (b) There was a significant relationship between decreased HIPc-LAG connectivity and decreased memory performance. (c) There was a significant relationship between increased HIPc-RAG connectivity and reduced memory performance (two-tailed, no correction). Memory performance was evaluated using the CVFT. All scores were calculated using post-ECT scores subtracted from pre-ECT scores (two-tailed, no correction). The red point was regarded as singular data (defined as outside three standard deviations of the mean) and was not included in correlation analysis. ECT, electroconvulsive therapy; RSFC, resting-state functional connectivity; HIPc, hippocampal cognitive region; LAG, left angular gyrus; RAG, right angular gyrus; FWE, family-wise error; CVFT, Category Verbal Fluency Test.

Fig. 4.

(a) Probabilistic tractography results (yellow) between the HIPe (blue) and LMOG (red), (b) as well as between the HIPc (blue) and LAG (red) are shown in the MNI space. Probabilistic maps were summed for pre-ECT and post-ECT patients and masked (threshold = 0.01). Only the voxels where more than 70% of the subjects’ data overlapped are shown. No significant differences in fractional anisotropy were found across (c) HIPe-LMOG or (d) HIPc-LAG connectivity between pre and post-ECT patients using a spectrum of probability thresholds (0.01, 0.05, 0.10, 0.15). HIPe, hippocampal emotional region; LMOG, left middle occipital gyrus; HIPc, hippocampal cognitive region; LAG, left angular gyrus; MNI, Montreal Neurological Institute; ECT, electroconvulsive therapy.