The Neurobiological Effects of ECT: New MRI Review in Biological Psychiatry

Out on PubMed, from international researchers, is this review:

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

Ousdal OT, Brancati GE, Kessler U, Erchinger V, Dale AM, Abbott C, Oltedal L.Biol Psychiatry. 2021 May 31:S0006-3223(21)01340-8. doi: 10.1016/j.biopsych.2021.05.023. Online ahead of print.PMID: 34274106

The abstract is copied below:

Electroconvulsive therapy (ECT) is an established treatment choice for severe, treatment-resistant depression, yet its mechanisms of action remain elusive. Magnetic resonance imaging (MRI) of the human brain before and after treatment has been crucial to aid our comprehension of the ECT neurobiological effects. However, to date, a majority of MRI studies have been underpowered and have used heterogeneous patient samples as well as different methodological approaches, altogether causing mixed results and poor clinical translation. Hence, an association between MRI markers and therapeutic response remains to be established. Recently, the availability of large datasets through a global collaboration has provided the statistical power needed to characterize whole-brain structural and functional brain changes after ECT. In addition, MRI technological developments allow new aspects of brain function and structure to be investigated. Finally, more recent studies have also investigated immediate and long-term effects of ECT, which may aid in the separation of the therapeutically relevant effects from epiphenomena. The goal of this review is to outline MRI studies (T1, diffusion-weighted imaging, proton magnetic resonance spectroscopy) of ECT in depression to advance our understanding of the ECT neurobiological effects. Based on the reviewed literature, we suggest a model whereby the neurobiological effects can be understood within a framework of disruption, neuroplasticity, and rewiring of neural circuits. An improved characterization of the neurobiological effects of ECT may increase our understanding of ECT's therapeutic effects, ultimately leading to improved patient care.

Keywords: Antidepressant; Brain; Depression; Diffusion-weighted imaging; Electroconvulsive therapy (ECT); Magnetic resonance imaging (MRI); Magnetic resonance spectroscopy; Neuroimaging.

And from the text: 

This review focuses on MRI structural and biochemical changes associated with ECT. Based on the reviewed literature, we show that ECT causes broad volumetric expansions of brain gray matter in the post-treatment phase, which is likely to represent a mixture of therapeutic and nontherapeutic ECT-induced effects. Accordingly, attempts to link the gray matter volumetric changes to clinical response have produced mixed results. Measurements of gray matter diffusivity suggest that the changes are not due to fluid shifts, but instead represent plastic changes in the parenchyma itself. However, the exact biological underpinning of the volumetric expansions remains to be established. In contrast, investigations of the brain’s metabolite spectra, white matter properties, and functional connectivity suggest that ECT also has disruptive effects. Thus, we propose a mechanistic model, which includes a temporary disruption followed by augmented neuroplasticity and rewiring.

 ...In summary, although preclinical animal models have been useful in understanding the working mechanisms of ECT in depression, human MRI studies are important to delineate which aspects can be translated and which aspects may be unique to human populations. Based on the reviewed literature, we propose a model in which brain disruption, plasticity potentiation, and rewiring occur in sequence and ultimately explain immediate, short-, and long-term effects of ECT. Although evidence for our model is indirect, it may be a framework for understanding the neurobiological underpinning of ECT’s therapeutic effects and derive new testable hypotheses, which ultimately may bring the field forward.

This is an exciting paper, really a tour de force, with 145 references and those cool figures, particularly Fig. 2. The authors present a theory that tries to account for both the antidepressant and cognitive effects of ECT, and importantly, their time course. It is erudite, and a bit flashy. They also come dangerously close to linking antidepressant effects to cognitive side effects, something that Sackeim and the field decoupled decades ago. 

The authors are not modest,either:

While the theoretical basis and the indirect evidence for our model may at first seem compelling, the model needs to be tested more rigorously in future studies.

These authors, from the Global ECT-MRI Research Collaboration, deserve kudos for a very thoughtful, and perhaps a touch fanciful, review. 

All students of the search for elucidating the mechanism(s) of action of ECT should read this paper in full, ~30 minutes.