# Resting state connectivity: Biophysical basis for and improved fMRI measurements

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $1,011,725

## Abstract

Principal Investigators(Last, first, middle):KLEINFELD, DAVID and ROSEN, BRUCE R.
 Functional magnetic resonant imaging (fMRI) is the only means to infer neuronal activity within the
entire volume of the human brain. A powerful aspect of fMRI concerns coordinated fluctuations in the
amplitude of blood oxygen level dependent (BOLD) signals across distant regions of the brain, which
are interpreted as "resting-state functional connections". Here we address the underlying biophysical
mechanism that underlies resting-state functional connectivity. Our hypothesis is that the natural
ultra-low frequency oscillations in the smooth muscle of arteriole walls, termed vasomotion, acts as
an intermediate oscillator that links oscillations in neuronal activity with the blood oxygenation and
thus fMRI signals. Rodent models permit us to test this hypothesis through detailed two-photon
imaging, advanced fMRI measurements, and manipulations of cortical vascular dynamics and blood
oxygenation under controlled conditions. We then advance the spatial resolution of ultra high field MR
imaging in humans to image single intracortical vessels, with 100 micrometer or better resolution, to
test whether vasomotion may be a unifying mechanism for resting and task-driven fMRI signals. The
results of these studies have two consequences. One is to provide the underpinnings for interpreting
resting state connectivity relative to neuronal projections. The second is a new model of mapping
functional connections via changes in arteriole volume. In particular, the strong homologies between
the physiology of rodents and primates suggest that these methods can be extended to map resting-
state functional connections in the human brain with higher resolution and greater precision than
previously achieved. This new mechanistic insight will advance our use of fMRI to study cognition and
a variety of neuropsychiatric disorders.

## Key facts

- **NIH application ID:** 9990859
- **Project number:** 5R01MH111438-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Kleinfeld
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,011,725
- **Award type:** 5
- **Project period:** 2016-09-16 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990859

## Citation

> US National Institutes of Health, RePORTER application 9990859, Resting state connectivity: Biophysical basis for and improved fMRI measurements (5R01MH111438-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9990859. Licensed CC0.

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