The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.

Previous animal models and structural imaging investigations have linked hippocampal neuroplasticity to electroconvulsive therapy (ECT) response, but the relationship between changes in hippocampal volume and temporal coherence in the context of ECT response is unknown. We hypothesized that ECT response would increase both hippocampal resting-state functional magnetic resonance imaging connectivity and hippocampal volumes. Patients with major depressive disorder (n=19) were scanned before and after the ECT series. Healthy, demographically matched comparisons (n=20) were scanned at one-time interval. Longitudinal changes in functional connectivity of hippocampal regions and volumes of hippocampal subfields were compared with reductions in ratings of depressive symptoms. Right hippocampal connectivity increased (normalized) after the ECT series and correlated with depressive symptom reduction. Similarly, the volumes of the right hippocampal cornu ammonis (CA2/3), dentate gyrus and subiculum regions increased, but the hippocampal subfields were unchanged relative to the comparison group. Connectivity changes were not evident in the left hippocampus, and volume changes were limited to the left CA2/3 subfields. The laterality of the right hippocampal functional connectivity and volume increases may be related to stimulus delivery method, which was predominately right unilateral in this investigation. The findings suggested that increased hippocampal functional connectivity and volumes may be biomarkers for ECT response.

Although a number of recent studies have examined functional connectivity at rest, few have assessed differences between connectivity both during rest and across active task paradigms. Therefore, the question of whether cortical connectivity patterns remain stable or change with task engagement continues to be unaddressed. We collected multi-scan fMRI data on healthy controls (N = 53) and schizophrenia patients (N = 42) during rest and across paradigms arranged hierarchically by sensory load. We measured functional network connectivity among 45 non-artifactual distinct brain networks. Then, we applied a novel analysis to assess cross paradigm connectivity patterns applied to healthy controls and patients with schizophrenia. To detect these patterns, we fit a group by task full factorial ANOVA model to the group average functional network connectivity values. Our approach identified both stable (static effects) and state-based differences (dynamic effects) in brain connectivity providing a better understanding of how individuals’ reactions to simple sensory stimuli are conditioned by the context within which they are presented. Our findings suggest that not all group differences observed during rest are detectable in other cognitive states. In addition, the stable differences of heightened connectivity between multiple brain areas with thalamus across tasks underscore the importance of the thalamus as a gateway to sensory input and provide new insight into schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. METHODS: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. RESULTS: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean 6 SD of 1.04 6 1.03% (Cohen's d = 1.01, p , .001) and the subcortical gray matter volume increased by 1.47 6 1.05% (d = 1.40, p , .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation r = 2.44, p , .001), while total white matter volume remained unchanged (d = 20.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. CONCLUSIONS: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

Major depressive disorder (MDD) is associated with increased functional connectivity in specific neural networks. Electroconvulsive therapy (ECT), the gold-standard treatment for acute, treatment-resistant MDD, but temporal dependencies between networks associated with ECT response have yet to be investigated. In the present longitudinal, case–control investigation, we used independent component analysis to identify distinct networks of brain regions with temporally coherent hemodynamic signal change and functional network connectivity (FNC) to assess component time course correlations across these networks. MDD subjects completed imaging and clinical assessments immediately prior to the ECT series and a minimum of 5 days after the last ECT treatment. We focused our analysis on four networks affected in MDD: the subcallosal cingulate gyrus, default mode, dorsal lateral prefrontal cortex, and dorsal medial prefrontal cortex (DMPFC). In an older sample of ECT subjects (n = 12) with MDD, remission associated with the ECT series reverses the relationship from negative to positive between the posterior default mode (p_DM) and two other networks: the DMPFC and left dorsal lateral prefrontal cortex (l_DLPFC). Relative to demographically healthy subjects (n = 12), the FNC between the p_DM areas and the DMPFC normalizes with ECT response. The FNC changes following treatment did not correlate with symptom improvement; however, a direct comparison between ECT remitters and non-remitters showed the pattern of increased FNC between the p_DM and l_DLPFC following ECT to be specific to those who responded to the treatment. The differences between ECT remitters and non-remitters suggest that this increased FNC between p_DM areas and the left dorsolateral prefrontal cortex is a neural correlate and potential biomarker of recovery from a depressed episode.