# Neurons, Vessels and Voxels:  Multi-modal Imaging of Layer Specific Signals

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $985,474

## Abstract

PROJECT SUMMARY
Our knowledge of signal processing in various parts of the human brain has been heavily influenced by non-
invasive functional magnetic resonance imaging (fMRI) experiments. FMRI infers the location and selectivity of
neural activity from vascular signals. However, brain circuits are much more complex than regional differences
in neuronal selectivity. Specifically, the largest part of the brain (neocortex) accounts for up to 80% of the brain
volume and is divided into six distinct layers. Specific computations, e.g., local processing vs. feedforward
inputs vs. vs. feedback inputs, are done in specific cortical laminae. Thus, if high-resolution layer-specific fMRI
is shown to reflect the repertoire of neural computations performed across these cortical layers, it would be an
invaluable refinement to non-invasive imaging. However, despite the widespread usage of low-resolution fMRI,
a detailed understanding of how neural activity generates vascular responses remains unknown.
 The goal of this project is to elucidate the link between neural and vascular signals across laminae by
combining two-photon imaging of neural and vascular responses with ultra-high-field (UHF) fMRI. Experiments
will use sensory visual stimuli that induce layer-specific responses. In cat primary visual cortex (V1), which has
a functional architecture (e.g., maps for stimulus orientation) similar to human V1, we will measure neural
activity (synaptic and spiking) with single-cell resolution together with vascular signals (blood flow, blood
volume, and oxygenation) in individual vessels across the entire cortical thickness. We will also perform UHF
lamina-specific fMRI in cat (9.4 and16.4 T) and human (7 and 10.5 T) V1 to relate fMRI signals to the single-
vessel responses. Lastly, we will develop a model to relate lamina-specific vascular signals to neural activity.
 In Aim 1, we test the hypothesis that vascular signals selective for stimulus orientation are present in
cortical layers 2/3 (and 5/6) while untuned responses occur in layer 4 and pial vessels. Grating visual stimuli
will be used, while varying orientation and eye preference (ocular dominance) systematically. Since binocular
integration is stronger outside layer 4, eye preference vascular signals should be most prominent in layer 4. In
Aim 2, we will test the hypothesis that in any given cortical lamina, glutamate release in regions around an
individual blood vessel best accounts for the selectivity of vascular responses compared to spiking activity—in
terms of the preferred stimulus orientation and tuning width. Aim 3 is to build a computational model to
determine effective minimum voxel size for BOLD fMRI. The model will be tested against simultaneously
measured vascular and neural activity to natural scene stimuli using two-photon imaging.
 If the source signals at the finest spatial scales have laminar specificity, we can correlate laminar-specific
fMRI signals to differences in neural processin...

## Key facts

- **NIH application ID:** 9960579
- **Project number:** 5R01MH111447-05
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Prakash Kara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $985,474
- **Award type:** 5
- **Project period:** 2016-09-21 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960579

## Citation

> US National Institutes of Health, RePORTER application 9960579, Neurons, Vessels and Voxels:  Multi-modal Imaging of Layer Specific Signals (5R01MH111447-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9960579. Licensed CC0.

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