# Distributed networks underlying depression in epilepsy: a computational circuit-based approach to biomarker development

> **NIH NIH K23** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $200,178

## Abstract

PROJECT SUMMARY/ABSTRACT
 Adult patients with epilepsy have an increased prevalence of major depression and other psychiatric co-
morbidities. Depression in epilepsy is associated with worse outcome and quality of life. However, it continues
to be underdiagnosed and untreated and further attention to this comorbidity is critical. My career goal is to
become an academic neuroscientist and clinician focused on understanding the neural networks underlying co-
morbid mood and anxiety spectrum disorders in patients with epilepsy.
 Specific brain circuits may underlie depression and be commonly affected by different precipitants (i.e. stress,
inflammation, epilepsy). In this proposal, our model is that a set of neural features across these brain circuits will
be shared across many patients with co-morbid depression. Evidence for a strong relationship between epilepsy
and depression includes the presence of depression symptoms before, during, after, and in between seizures,
evidence of cases of concurrent onset of depression and epilepsy, an increased incidence of interictal
depression when limbic structures are involved in seizure occurrence, and evidence that depression scores may
be lower after surgical resection for medication refractory epilepsy. Intracranial electroencephalography (iEEG)
captured during the pre-surgical recording period offers a particularly promising method to study depression
networks in adult epilepsy, offering both high temporal resolution and spatial precision. Despite the enormous
potential of iEEG, there are no studies to date that examine the neurophysiological signatures of network
dysfunction in mood and anxiety disorders in patients with epilepsy. Such studies are critical in order to better
understand the etiology of co-morbid depression and could lead to novel personalized therapies.
 In our pilot work, we identify a set of power spectral measures within a corticolimbic circuit that appear to be
linked to depression and are, therefore, a potential biomarker of co-morbid depression. We also found evidence
that supports the basis for testing whether neural features will predict treatment outcome. This proposal builds
on these preliminary findings to validate our model and test the hypothesis that a set of neural features is shared
across some subjects with MDD in epilepsy and is detectable with machine-learning techniques applied to
interictal iEEG recordings. Aim 1 demonstrates the relationship between resting state neural circuit abnormality
and depression. Aim 2 tests whether removing the dysfunctional region of the circuit improves depression and
whether the presurgical resting state iEEG predicts that improvement.
 To address these research goals, I will need more rigorous training in computational neuroscience for complex
datasets, advanced signal processing, and biostatistics. My training plan and carefully selected mentoring and
advisory team across fields of psychiatry, neurosurgery, neurology and statistics wi...

## Key facts

- **NIH application ID:** 10238999
- **Project number:** 5K23NS110962-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Katherine W Scangos
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $200,178
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238999

## Citation

> US National Institutes of Health, RePORTER application 10238999, Distributed networks underlying depression in epilepsy: a computational circuit-based approach to biomarker development (5K23NS110962-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10238999. Licensed CC0.

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