# Ascertaining Neurocircuitry to Enhance Neuromodulation Development ASCEND

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $563,330

## Abstract

PROJECT ABSTRACT
Major depressive disorder (MDD) is ranked second among all diseases in global impact. Unfortunately, many
patients have treatment-resistant MDD (TRD), for which the most effective antidepressant treatment option is
electroconvulsive therapy (ECT). However, the neurocognitive adverse effects (e.g., anterograde and
retrograde amnesia) induced by ECT mitigate the attainment of desired clinical outcomes. As such, the
development of new and safe neuromodulatory antidepressant interventions is strongly warranted. One new
type of neuromodulation treatment that has antidepressant properties and is under active development is
magnetic seizure therapy (MST). MST is neurocognitively safer than ECT because it uses magnetic rather than
electrical fields to induce seizures, which have shallower penetration and therefore avoid the undesired side-
effect of delivering intense electrical stimulation to the medial temporal lobe. As yet there has been no research
into the neuromechanisms underlying MST’s antidepressant and neurocognitive effects. To systematically
uncover these mechanisms, we are building upon an international, NIMH funded (R01 MH112815), US Food
and Drug Administration Investigational Device Exemption (IDE; #G170127) approved clinical study that will
compare and contrast clinical and neurocognitive outcomes of ECT and MST. The goal of this R01 is to
conduct research Ascertaining Neurocircuitry to Enhance Neuromodulation Development (ASCEND). In
the proposed study, we will capitalize on that project by adding advanced magnetic resonance imaging (MRI),
individualized 3-D computational head modeling of ECT and MST (E-fields in stimulated brain regions), and
neurophysiological modeling of activity propagation and plasticity resulting from each treatment type. This
innovative 5-year project has two aims: 1) Determine the common and distinct neural circuit correlates of
antidepressant treatment response between RUL-UB-ECT and MST, and 2) Determine the common and
distinct neural circuit correlates of memory side effects between RUL-UB-ECT and MST. The proposed study
will draw upon an interdisciplinary team from diverse backgrounds including translational neurocognitive
science, neuropsychology, computational neuroscience, psychiatry, neuroimaging, bioengineering, and
biostatistics. The synthesis of physical (E-field) and physiological (neural activity and dynamics) computational
modeling and MRI with the clinical and neurocognitive metrics from the current NIMH-funded clinical trial will
allow us to determine neuromodulation-induced changes in neurocircuitry, and their corresponding
relationships to behavior. Such knowledge will elucidate the neural mechanisms of antidepressant seizure
therapy (ECT, MST) to inform new treatment methods that optimally target neurocircuitry related to symptom
improvement, while ensuring neurocognitive safety. These developments will make a major contribution to
improving the lives of the many patients with...

## Key facts

- **NIH application ID:** 9908175
- **Project number:** 5R01MH119285-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Colin Hawco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,330
- **Award type:** 5
- **Project period:** 2019-04-05 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908175

## Citation

> US National Institutes of Health, RePORTER application 9908175, Ascertaining Neurocircuitry to Enhance Neuromodulation Development ASCEND (5R01MH119285-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9908175. Licensed CC0.

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