The Neurobiological Effects of Electroconvulsive Therapy Studied Through Magnetic Resonance: What Have We Learned, and Where Do We Go?

Ousdal, Olga Therese; Brancati, Giulio Emilio; Keßler, Ute; Erchinger, Vera Jane; Dale, Anders M.; Abbott, Christopher; Oltedal, Leif

doi:10.1016/j.biopsych.2021.05.023

Cited by 47 publications

(35 citation statements)

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“…A recent review summarized that the activity and connectivity in the prefrontal are the most consistent ECT antidepressant-response fMRI biomarkers [48]. The implications of reduced fALFF may also be consistent with the recent conceptualization of temporary disruption (reduced fALFF) followed by neuroplasticity and rewiring [49]. This model specifies that the optimal level of disruption and neuroplasticity will be associated with antidepressant response and cognitive safety.…”

Section: Discussionmentioning

confidence: 58%

“…Fifth, the voxel-wise GMV used in this study was generated from the basic voxel-based morphometry (VBM), not by the DARTEL that may improve the estimation of GMV. However, the majority of the previous published ECT sMRI analyses were based on VBM with increased hippocampus GMV after ECT is a consistent treatment response neuroimaging marker [17,49]. Finally, the seizure was an essential therapeutic component of ECT and was not included in this investigation.…”

Section: Discussionmentioning

confidence: 99%

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Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder

Calhoun

Zhang

et al. 2022

BMC Med

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Background Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation. Methods A single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks. Results Decreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7–113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety. Conclusions The large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit–risk ratio. Trial registration ClinicalTrials.gov Identifier: NCT02999269.

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder

Calhoun

Zhang

et al. 2022

BMC Med

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“…Regarding the imaging findings in this patient, although MRI has been used to evaluate structural changes related to long-term use of ECT and largely shows regional volumetric changes or differences in fractional anisotropy in different white matter tracts, there are few reports of MRI findings concerning for ischemia but none similar to the findings in this patient [ 33 , 34 ]. There are rare reports of acute ischemic strokes following ECT, but our imaging pattern was not that of an arterial ischemic stroke [ 33 , 34 ]. Overall, the MRI findings in the patient presented in this report are not consistent with reported imaging changes associated with ECT.…”

Section: Discussionmentioning

confidence: 99%

Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report

et al. 2022

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Background Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders. Case The patient received unilateral ECT to the right side and subsequently had an episode of SE with right-sided hemiplegia for 72 h prior to regaining some function with persistent mild right-hand weakness that persisted for at least 1–2 weeks. A brain MRI 2 days after ECT was unremarkable, but a repeat MRI on day four of admission showed left hemisphere cortical diffusion restriction, increased perfusion and T2 prolongation suggestive of cortical edema. They had whole exome genetic testing sent after discharge that showed a known pathogenic CACNA1a variant (p.I1709T). CACNA1a encodes the P/Q type calcium channels and deleterious variants in this gene result in a channelopathy associated with a spectrum of neurodevelopmental disorders that include autism spectrum disorder, hemiplegic migraine with unilateral cerebral edema, epileptic encephalopathies, or episodic ataxia syndromes. Conclusion A literature review of ECT and neurologic deficits showed that most neurologic deficits resolve within 30 min of ECT. Case reports of prolonged deficits are rare and there are no prior reports of acute MRI changes related to ECT. Thus, the acute deterioration and MRI findings in this patient are likely related to the underlying CACNA1a channelopathy disorder with ECT as a precipitating event. This case report suggests care should be taken when using ECT in patients with pathogenic variants in CACNA1a. Furthermore, it reinforces the utility and importance of expanded genetic testing in patients with neurodevelopmental disorders as findings can provide valuable information that can guide treatment decisions.

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“…ECT cognitive meta-analyses demonstrate acute but transient cognitive impairment immediately after the acute phase of the series ( Semkovska and McLoughlin, 2010 ; Semkovska et al, 2011 ). Numerous mechanisms of ECT cognitive impairment have been proposed, including excessive neuroplasticity and disrupted long-term potentiation ( Ousdal et al, 2022 ). However, the findings on ECT-induced changes in cognition are somehow contradictory, with substantial cognitive deficits ( Sackeim et al, 2007 ; Semkovska and McLoughlin, 2010 ) and improvement in cognitive function ( Bosboom and Deijen, 2006 ; Fujita et al, 2006 ) documented in the literature.…”

Section: Introductionmentioning

confidence: 99%

Predictive signature of static and dynamic functional connectivity for ECT clinical outcomes

Abbott

Sui

et al. 2023

Front. Pharmacol.

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Introduction: Electroconvulsive therapy (ECT) remains one of the most effective approaches for treatment-resistant depressive episodes, despite the potential cognitive impairment associated with this treatment. As a potent stimulator of neuroplasticity, ECT might normalize aberrant depression-related brain function via the brain’s reconstruction by forming new neural connections. Multiple lines of evidence have demonstrated that functional connectivity (FC) changes are reliable indicators of antidepressant efficacy and cognitive changes from static and dynamic perspectives. However, no previous studies have directly ascertained whether and how different aspects of FC provide complementary information in terms of neuroimaging-based prediction of clinical outcomes.Methods: In this study, we implemented a fully automated independent component analysis framework to an ECT dataset with subjects (n = 50, age = 65.54 ± 8.92) randomized to three treatment amplitudes (600, 700, or 800 milliamperes [mA]). We extracted the static functional network connectivity (sFNC) and dynamic FNC (dFNC) features and employed a partial least square regression to build predictive models for antidepressant outcomes and cognitive changes.Results: We found that both antidepressant outcomes and memory changes can be robustly predicted by the changes in sFNC (permutation test p < 5.0 × 10−3). More interestingly, by adding dFNC information, the model achieved higher accuracy for predicting changes in the Hamilton Depression Rating Scale 24-item (HDRS24, t = 9.6434, p = 1.5 × 10−21). The predictive maps of clinical outcomes show a weakly negative correlation, indicating that the ECT-induced antidepressant outcomes and cognitive changes might be associated with different functional brain neuroplasticity.Discussion: The overall results reveal that dynamic FC is not redundant but reflects mechanisms of ECT that cannot be captured by its static counterpart, especially for the prediction of antidepressant efficacy. Tracking the predictive signatures of static and dynamic FC will help maximize antidepressant outcomes and cognitive safety with individualized ECT dosing.

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The Neurobiological Effects of Electroconvulsive Therapy Studied Through Magnetic Resonance: What Have We Learned, and Where Do We Go?

Cited by 47 publications

References 147 publications

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder

Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder

Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report

Predictive signature of static and dynamic functional connectivity for ECT clinical outcomes

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