Advanced functional MRI of cerebral cortical layers in the human brain using ultrahigh-resolution linescan MRI technology

The National Institute of Mental Health (NIMH) awarded a $156,656 Project Grant under the Mental Health Research Grants (CFDA 93.242) program to The General Hospital Corporation (doing business as Massachusetts General Hospital) to advance functional MRI (fMRI) techniques for mapping brain activity across cerebral cortical layers. The project aims to validate and benchmark a "linescan fMRI" method that can achieve higher spatial resolution than conventional laminar fMRI, enabling improved understanding of brain circuitry. The 3-year project, starting on March 1, 2025, will first assess signal-to-noise differences between 2D and 1D linescan acquisitions, then validate linescan fMRI by replicating established findings on visual processing, and finally apply the technique to map population receptive fields and attentional modulation across cortical layers. This research is expected to advance the use of high-resolution fMRI for studying higher-order cognition in the human brain.

Abstract

Research: functional MRI (FMRI) has contributed enormously to our understanding of human brain function. Today all FMRI methods use hemodynamics as an indirect proxy for brain function, and recent evidence has shown that these hemodynamics are regulated at the level of cerebral cortical layers. Cortical layers act as inputs and outputs of large-scale brain networks, making IT crucial to measure activity across individual cortical layers to decipher brain circuitry. However, despite advanced instrumentation and ultra-high field (≥7 tesla) MRI scanners, current laminar MRI methods are limited due to voxel sizes that still exceed the thickness of individual cortical layers. To address this limitation, we propose to advance "linescan FMRI" a classic method that acquires a one-dimensional (1D) single "line" of imaging data. This method sacrifices spatial coverage for very high spatial resolution along the line, making IT ideal for laminar MRI. Linescan FMRI is thus analogous to classic invasive laminar electrode recordings, facilitating comparisons of FMRI findings with electrophysiology. Despite recent progress in linescan FMRI technology, there have been limited demonstrations of its utility for human neuroscience, and direct comparisons against conventional laminar FMRI and comprehensive characterization are needed. The proposed set of experiments will fill this GAP and benchmark linescan FMRI both by confirming that IT can be used to map known patterns of activation across layers and by applying IT to novel human neuroscience experiments. First, we will address any existing concerns about signal-to-noise ratio (SNR) in aim 1 and directly assess SNR differences between 2D and 1D linescan acquisitions using both phantom scans and human studies. Aim 2 will validate linescan FMRI by comparing IT to conventional high-resolution FMRI, by replicating established findings using visual stimulation and acquiring data from primary visual cortex (V1). Finally, aim 3 will apply linescan FMRI to map population receptive fields across layers in V1, whose profile is well established, and measure attentional modulation across layers, with the goal of replicating findings from prior gold-standard monkey electrophysiology experiments. Environment & training: my environment is ideally suited for the proposed training. Drawing on their expertise, my sponsor and CO-sponsor will train me in MR physics, laminar FMRI, neurovascular coupling, hemodynamics, and human subjects research. My sponsor is an expert in high-resolution FMRI technology and laminar FMRI, thus will provide ideal mentorship and training for my goals. My mentoring team, research facilities and infrastructure at the massachusetts general hospital and the martinos center will further support my proposed training. My training will consist of direct mentoring and didactic training including workshops in ultra-high-field FMRI, trainings offered at larger scientific meetings, and local courses in professional development, scientific communication, mentorship, and responsible conduct of research. This training will prepare me for a career as an independent researcher applying leading-edge FMRI methods to understanding higher-order cognition.