# A Transdiagnostic Assessment of Electroconvulsive Therapy Modulation of Anhedonia and Reward circuitry: Targets, Biomarkers and Predictors of Response

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $182,349

## Abstract

Electroconvulsive Therapy (ECT) is the most effective treatment in psychiatry, and among the most
effective in medicine. Despite its apparent non-focal effects leading to a generalized seizure, its therapeutic
benefits are specific to a few clinical syndromes, including major depressive disorder (MDD) and bipolar
depression (BD). These two syndromes share core deficits in reward processing (i.e. anhedonia). ECT
improves anhedonia across mood disorders and syndromes, implying selective effects on the functional
dynamics and structural properties of reward networks.
 Reward-related functions represent key behavioral dimensions of pathological relevance across
neuropsychiatric disorders, and have a central place as positive valence constructs in the RDoC matrix. There
has been a growing recognition that “anhedonia” does not represent a unitary dimension; among its
subcategories, three constructs emerge with clear relevance to behavior and disease: consummation (liking),
motivation (wanting) and reinforcement (learning). Quantitative behavioral measures exist for each of these
three, with clinical validity as biomarkers and predictors of response.
 The anatomy of the reward network is well known, with a core in the ventral tegmental area (VTA) and
the Nucleus Accumbens (NAc), and projections to cortical and subcortical nodes via the mesocorticolimbic
pathway and its ramifications. The Human Connectome Project (HCP) has significantly advanced the
technologies for imaging brain connections in humans, accelerating innovation in the emerging field of
Connectomics. Preliminary data from our group describes the feasibility of obtaining multimodal MRI measures
of reward circuit biology (morphometry, tractography, functional connectivity) in patients undergoing ECT, and
extracting clinically meaningful information to identify treatment targets and develop biomarkers and predictors.
 At a time when therapeutic research is stalled due to the absence of clear targets and useful
biomarkers, understanding the mechanisms of our most effective treatments is a priority for our field. In this
study, we propose a novel translational strategy that takes advantage of the high efficacy and fast response of
ECT, and uses it to probe target engagement at the circuit level. With a systems neuroscience framework, in
line with NIMH strategic priorities and the RDoC Initiative, we will focus on reward circuitry and its clinical
dimensions across two clinical syndromes that are commonly treated with ECT: MDD and BD. We will use
HCP multimodal MRI protocols combined with validated behavioral measures of reward constructs to assess
patients before, during and after ECT, in addition to a cohort of matched healthy controls that will be imaged
twice. This study is innovative in its proposal to combine ECT with multimodal MRI as a framework to study
anhedonia transdiagnostically, with the translational aims to (1) discover treatment targets, (2) develop
biomarkers and (3) identify pr...

## Key facts

- **NIH application ID:** 10149708
- **Project number:** 3R01MH112737-04S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Joan A Camprodon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,349
- **Award type:** 3
- **Project period:** 2017-07-05 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149708

## Citation

> US National Institutes of Health, RePORTER application 10149708, A Transdiagnostic Assessment of Electroconvulsive Therapy Modulation of Anhedonia and Reward circuitry: Targets, Biomarkers and Predictors of Response (3R01MH112737-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10149708. Licensed CC0.

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