# A Multi-Modal Investigation of Neurophysiological Deficits in PTSD

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $150,850

## Abstract

Project Summary
 Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered neural circuitry
underlying threat and emotion processing. PTSD is twice as prevalent in women than men, and menstrual cycle
phase has been implicated in sex differences, but the neural circuitry of PTSD is poorly characterized in women.
A consistent finding is that PTSD is associated with increased resting state activity of dorsal anterior cingulate
cortex (dACC) and decreased activity of ventromedial prefrontal cortex (vmPFC), reflecting exaggerated
emotional responding and dampened emotion regulation, respectively. PTSD is also associated with decreased
functional connectivity in the theta frequency range (4-7 Hz). The dACC appears to be a generator of theta range
brain activity, which has been implicated in PTSD; however, no prior research has probed theta-based resting
state dACC and vmPFC activity, or theta-based dACC-vmPFC connectivity in PTSD. Further, no prior research
has examined these effects in women based on menstrual cycle phase. In addition to resting state deficits, fear
conditioning studies have shown that PTSD is associated with increased late positive potential (LPP) amplitudes
in response to fearful stimuli, reflecting exaggerated emotional encoding. While there are well-established effects
of menstrual cycle phase on the LPP, no prior research has tested these effects in women with PTSD.
Characterization of this neural circuitry and the moderating role of menstrual cycle phase represent critical gaps
in understanding how women experience greater risk for PTSD.
 To address these unmet needs, we will take a multi-modal approach to PTSD brain circuitry by testing
resting state and event-related neurophysiological deficits in trauma-exposed women with and without PTSD.
We will use high-density EEG to probe theta-based resting state activity of the dACC and vmPFC, as well as
dACC-vmPFC functional connectivity in PTSD. We will then probe event-related deficits by measuring the LPP
and its underlying cortical sources during fear conditioning. Finally, we will collect estradiol and progesterone to
determine menstrual cycle phase and test its moderating effects on these phenomena. The applicant will learn
to use state-of-the-art physiological methods such as standardized Low Resolution Electromagnetic
Tomography (sLORETA), power envelope connectivity analyses, ERPs with source localization, and serum
hormone assays. Using the temporal resolution of high-density EEG, this study will provide a more nuanced and
mechanistic understanding of fear circuitry deficits in women with PTSD. Our overall goal is directly in line with
Objective 1 of the NIMH’s Strategic Plan: “Define the Mechanisms of Complex Behaviors.” Specifically, the
proposal will further elucidate the neurophysiological circuits and mechanisms underlying PTSD in women. By
leveraging advanced EEG techniques, this study will ultimately contribute to the improvement of PTS...

## Key facts

- **NIH application ID:** 10833554
- **Project number:** 5K23MH125920-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Antonia Seligowski
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $150,850
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833554

## Citation

> US National Institutes of Health, RePORTER application 10833554, A Multi-Modal Investigation of Neurophysiological Deficits in PTSD (5K23MH125920-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10833554. Licensed CC0.

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