Keywords: fMRI Analysis, High-Field MRI, Brain, Neuro

Motivation: Hemodynamic responses in adults vary across cortical depths, partly due to specific differences in vascular anatomy and physiology. It is unknown how these differences relate to the responses seen in neonates, when the cortex and neurovasculature are rapidly maturing.

Goal(s): To characterize the amplitude and timing of the hemodynamic response across cortical depths during the neonatal period.

Approach: Cortical depth-dependent hemodynamic responses to sensorimotor stimulation were delineated using GRE-BOLD fMRI in term-aged neonates.

Results: A cortical depth-specific profile of key hemodynamic response parameters, including onset and undershoot, was observed in the neonatal cortex that differs from those seen in the adult.

Impact: We demonstrate for the first time how developing vascular network may alter hemodynamic response across cortical depths. It illuminates what underlying neurobiology may generate the neonatal specific BOLD signal profile and what components are altered relative to the adult response.

Keywords: fMRI Acquisition, fMRI, layer-fMRI, Ultra High Field, Structural scan

Motivation:  High-resolution fMRI at 7T is limited by misregistration of functional data with structural scans.

Goal(s): We aim to provide a fast acquisition method that provides distortion matched, artifact mitigated structural reference data.

Approach: T1234: T1-weighted 2-inversion 3D-EPI with 4 directions for high-resolution fMRI. A forward Bloch model is implemented for T1 quantification and protocol optimization.

Results: Our protocol is fast (3:40 min) and provides whole-brain segmentations in EPI-space. It is robust across sessions, participants, and scanners.

Impact: This structural mapping approach allows precise registration with fMRI data. T1234 is implemented, validated, and tested to serve users of our sequence (locally and 43 centers worldwide).

Keywords: fMRI Analysis, fMRI, fMRI Analysis, fMRI (task based), Brain, Gray Matter, Neuroscience, Blood, Data Analysis

Motivation: Laminar-fMRI analysis routinely averages cortical-depth profiles within an ROI to estimate a typical laminar activation profile and increase SNR. Previous studies suggested heterogeneity of cortical-depth profiles measured with GE-BOLD-fMRI, therefore the assumption that profiles inside ROI are similar may not hold.

Goal(s): To test whether the average cortical-depth profile is typical for the whole ROI.

Approach: We applied k-means clustering to identify cortical locations within an ROI with similar BOLD-fMRI cortical-depth profiles.

Results: Cortical-depth profiles vary substantially across the activated region and therefore the average response profile inside the ROI may not be resemble that of any particular activated location.

Impact: In laminar-fMRI analysis, due to heterogeneity of neuronal responses and/or vascular architecture the average cortical-depth profile within an ROI may not match the profile at any one location, suggesting that averaging may lose meaningful layer-specific information within the activated region.

Keywords: Task/Intervention Based fMRI, fMRI (task based)

Motivation: Layer-specific response in frontoparietal areas and their connectivity with the visual cortex are important to understand the neural circuitry of attention.

Goal(s): Investigate the neural circuitry of attention in IPS and V1 with laminar fMRI.

Approach: Using ultra-high resolution multi-echo bSSFP fMRI at 7 Tesla, layer-specific functional activity in IPS and V1 were simultaneously recorded in a spatial attention task.

Results: Attention demanding task induced significant activations in both superficial and deep layers of IPS, enhanced activity in the deep layers of V1, and increased feedback connectivity from the deep layers of IPS to the deep layers of V1.

Impact: This study demonstrates the feasibility of using ultra-high resolution multi-echo bSSFP fMRI at 7 Tesla to simultaneously image multiple brain regions to investigate the neural circuitry of high-level cognition.

Keywords: fMRI Acquisition, fMRI, Layer-dependent fMRI

Motivation: Mapping brain-wide directed functional connectivity demands techniques with high spatiotemporal resolution yet current methods fall short.

Goal(s): To improve spatial specificity of GE-BOLD EPI by reducing draining-vein contamination without compromising speed.

Approach: Incorporating velocity-nulling (VN) gradients into a GE-BOLD fMRI sequence at 3T. We also integrated NORDIC denoising to enhance signal sensitivity.

Results: The VN fMRI method demonstrated decent spatial specificity, evidenced by identifying double-peak activation patterns within the M1 area during a finger-tapping task. This technique showed enhanced robustness across participants compared to conventional fMRI. Our findings on directed functional connectivity reveal layer-specific relationships that closely align with the existing literature.

Impact: Leveraging its comprehensive brain coverage and efficient scan time, VN fMRI has yielded promising results in directed FC studies. Given the widespread accessibility of 3T scanners, we anticipate this development will have a significant impact across multiple neuroscience research domains.

Keywords: Task/Intervention Based fMRI, fMRI (task based), Neuroscience

Motivation: Submillimeter fMRI allows imaging the human brain noninvasively at the mesoscopic scale, targeting layers and columns. Standard submillimeter resolution however may be inadequate to fully capture these ensembles. Consequently, the Brain Initiative challenged the MR community to achieve 0.1µL, and subsequently, 0.01µL voxel resolution

Goal(s): Achieve and surpass the goal of human functional mapping at 0.1µL, towards the goal of 0.01µL using a 10.5T scanner.

Approach: We recorded human functional BOLD responses at 10.5T, during visual experiments, at different spatial resolutions.

Results: Using 10.5T and NORDIC denoising we demonstrate functional imaging the human brain with <0.1µL resolution.
 

Impact: We demonstrate functional mapping at 10.5 T with unprecedented spatial resolutions, moving towards the 0.01µL voxel volume goal (Brain Initiative 2.0). At these resolutions single voxels contain a few thousand neurons, heralding major new opportunities in human neuroscience.

Keywords: Task/Intervention Based fMRI, High-Field MRI, Hippocampus, navigation

Motivation: Despite substantial progress in understanding the role of the hippocampus in spatial navigation, the layer-specific microcircuits underlying distinct navigation processes are yet to be determined.

Goal(s): We aimed to investigate the laminar organization of hippocampal subregions during spatial navigation including its relationship to specific strategies.

Approach: Leveraging submillimeter-resolution fMRI at 7T, we quantified BOLD signal changes across hippocampal depths and applied mixed-effect models to probe the relationship between subregional laminar activity and specific strategies reflected by straight paths and deviation towards environmental boundaries.  

Results: We show that laminar profiles in hippocampal subregions are differentially associated with navigation strategies.

Impact: Our results demonstrate the promise of laminar fMRI for mapping complex cognitive functions in the hippocampus at mesoscale. Given the vulnerability of this region to Alzheimer’s disease pathology, these findings may have clinical implications for early diagnosis.      

Keywords: Task/Intervention Based fMRI, fMRI (task based)

Motivation: While responses to feedforward inputs have been well-observed in layer-specific fMRI studies, our understanding of responses to feedback projections within the ongoing functional processing remains limited.

Goal(s): Our study aimed to investigate how synaptic onset and strength contribute to specificity of laminar fMRI responses.

Approach: We performed the ultrahigh resolution CBV-weighted laminar fMRI by modulating thalamocortical and corticocortical projections with stimulus onset asynchrony in mice.

Results: We observed that the laminar response is highly sensitive to the strength of synaptic inputs, shifting from early to later input sites with increased strength.

Impact: Laminar CBV responses are highly regulated by micro-vessels coupled with earlier synaptic input activity, but potentially driven by the most synchronous activity within neural circuits.

Keywords: Functional Connectivity, Brain Connectivity, BOLD, difusion fMRI, visual system, connective field model

Motivation: To disentangle feedback and feedforward signals in cortical circuits.     

Goal(s): To unravel the intricate neural connections within cortical layers.

Approach: We implemented a layer connective field (lCF) model and applied it to ultrafast RS data and RS dfMRI data.

Results: 1.Intracortical lCF shows two lCF size profiles: feedforward with inverse U shape with the larger lCF sizes at layer 5 and feedback with U shape and larger CF sizes at superficial and deeper layers. 2.In the absence of visual input the functional connectivity reflects visuotopic organization. 3.lCF estimates obtained from dfMRI(ADC) are more layer specific than the ones estimated from BOLD.

Impact: This study showcases the ability of high spatio-temporal resolution MRI techniques (ultrafast BOLD and dfMRI) when coupled with biologically grounded connectivity models (lCF) to unveil the intricacies of information directionality within topographically organized cortices.

Keywords: Task/Intervention Based fMRI, High-Field MRI, Arterial spin labeling, cortical layers, calibrated fMRI, CMRO2, negative BOLD

Motivation: To better understand the complex interplay between neurovascular responses and metabolism.

Goal(s): The goal was to develop a multi-contrast laminar fMRI tool to concurrently measure CBF, CBV, BOLD, and CMRO₂ signals.

Approach: We employed a novel pulse sequence to simultaneously acquire ASL CBF, VASO CBV, and T2-BOLD signals at a high spatial resolution of 7T. We also incorporated a calibrated fMRI approach (Davis model) to calculate CMRO₂, using parameters estimated from breath-hold induced hypercapnia.

Results: We found distinct neurovascular and metabolic responses across cortical layers and eccentricities in response to a ring-shaped visual stimulus.

Impact: Multi-contrast laminar fMRI significantly impacts neuroscientific research by providing a more comprehensive understanding of neurovascular (CBF, CBV, BOLD) and metabolic (CMRO₂) interactions across cortical layers. It opens doors for exploring complex brain functions and disorders.