# Neurobiological mechanisms of perceived stress and their modification through behavioral intervention

> **NIH NIH K01** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $134,830

## Abstract

PROJECT SUMMARY
Subjective perceptions of stress mediate the effects of acute and chronic stressors on long-term psychological
outcomes, and thus represent an important risk factor for disorders such as PTSD and depression. The proposed
project will fill a knowledge gap by identifying novel putative brain mechanisms of perceived stress, thus allowing
for better identification of at-risk individuals and the development of treatment targets for interventions that seek
to enhance stress resilience. This Career Development Award will provide the candidate with training in
advanced structural and diffusion-weighted MRI methods and didactic and mentored training in the fundamentals
of clinical trials research. This new training will be leveraged to test novel hypotheses regarding hippocampal
contributions to perceived stress, and modification of these mechanisms by a mindfulness intervention. In a
sample of 300 individuals from the community, Study 1 will investigate relationships between perceived stress
and pattern separation behavior, a hippocampal-dependent process that allows for fine-grained discrimination
of safe vs. threatening contexts, and which has been theoretically linked to over-generalization of fear and
negative affect. Using high-resolution structural imaging and multi-atlas segmentation of the hippocampus, Aim
1 will investigate relationships between pattern separation behavior, hippocampal subfield volumes, and
perceptions of daily life stressors and acute laboratory stressors. In Aim 2, advanced diffusion-weighted imaging
methods will be used to gain insight into the density and orientation of hippocampal neurites (axons and
dendrites). This will allow for a novel investigation of the microstructural correlates of subjectively perceived
stress, hypothesized to include reduced neurite density within the hippocampus and less coherent orientation of
white matter tracts linking the hippocampus and medial prefrontal cortex. In Study 2, 80 participants will be
randomized to a wait-list control group or mindfulness-based stress reduction (MBSR), which is known to reduce
subjective perceptions of stress. Aim 3 will test whether MBSR participants demonstrate improvements in pattern
separation behavior, hippocampal volume, and hippocampal microstructure, and whether these hippocampal
changes are associated with expected reductions in perceived stress. Aims 1-2 will be facilitated by new training
in advanced structural imaging of the hippocampus and advanced diffusion-weighted imaging methods,
supported by a training team with extensive expertise in these domains and made possible by the rich resources
of a world-class brain imaging center. Aim 3 will be supported by didactic, experiential, and mentored training in
the fundamentals of clinical research through the NIH-funded Institute for Clinical and Translational Research
(ICTR). Collectively, the research and training aims of this project seek to illuminate novel neurobiological
mechanisms ...

## Key facts

- **NIH application ID:** 9904327
- **Project number:** 5K01MH117222-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Daniel W Grupe
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $134,830
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904327

## Citation

> US National Institutes of Health, RePORTER application 9904327, Neurobiological mechanisms of perceived stress and their modification through behavioral intervention (5K01MH117222-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9904327. Licensed CC0.

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