Laminar-specific functional connectivity mapping with multi-slice line-scanning fMRI

Abstract

Laminar BOLD-fMRI has been applied to better depict the neuronal input and output circuitry and functional connectivity across cortical layers by measuring local hemodynamic changes. Despite extensive studies detecting laminar fMRI signals to illustrate the canonical microcircuit, the spatiotemporal characteristics of laminar-specific information flow across different cortical regions remain to be fully investigated in both evoked and resting states. Here, we developed a multi-slice line-scanning fMRI (MS-LS) method to detect laminar fMRI signals in adjacent cortical regions with high spatial (50 μm) and temporal resolution (100 ms) in anesthetized rats. Across different scanning trials, we detected both laminar-specific positive and negative BOLD responses in the surrounding cortical region adjacent to the most activated cortex under evoked condition. Specifically, in contrast to the typical Layer (L) 4 correlation across different regions due to the thalamocortical projections for trials with positive BOLD, a strong correlation pattern specific in L2/3 was detected for the trials with negative BOLD in adjacent regions, which indicate a brain state-dependent laminar-fMRI responses based on cortiocotical interaction from different trials. Also, we acquired the laminar-specific rs-fMRI signals across different cortical regions, of which the high spatiotemporal resolution allows us to estimate lag times based on the maximal cross-correlation of laminar-specific rs-fMRI signals. In contrast to the larger variability of lag times in L1 and 6, robust lag time differences in L2/3, 4, and 5 across multiple cortices represented the low-frequency rs-fMRI signal propagation from the caudal to the rostral slice. In summary, our work provides a unique laminar fMRI mapping scheme to better characterize trial-specific intra- and inter-laminar functional connectivity with MS-LS, presenting layer-specific spatiotemporal variation of both evoked and rs-fMRI signal.

Robust high spatio-temporal line-scanning fMRI in humans at 7T using multi-echo readouts, denoising and prospective motion correction

“…Line-scanning fMRI in rodents has also been used in combination with other techniques such as fiber-based optogenetic stimulation (Albers et al, 2018) and diffusion-sensitizing gradients (Nunes et al, 2021), to investigate the fast BOLD onset times at high spatial resolution. Line-scanning fMRI in rats has been extended towards a multi-line implementation, acquiring line profiles from different cortical regions to investigate laminar-specific functional connectivity mapping under both evoked and resting-state conditions (Choi et al, 2021).…”

Neuroimaging at ultra-high spatiotemporal resolutions: line-scanning fMRI

“…Line-scanning fMRI in rodents has also been used in combination with other techniques such as fiber-based optogenetic stimulation [301] and diffusion-sensitizing gradients [302], to investigate the fast BOLD onset times at high spatial resolution. Line-scanning fMRI in rats has been extended towards a multi-line implementation, acquiring line profiles from different cortical regions to investigate laminar-specific functional connectivity mapping under both evoked and resting-state conditions [303].…”

“…Line-scanning fMRI is such an approach. In contrast to conventional whole-brain acquisition, line-scanning allows extremely high spatial (250 μm) and temporal (∼100 ms) resolution in line direction by sacrificing volume coverage [50,303,306]. This is done by exciting a slice and suppressing the signal outside the line of interest through outer volume suppression (OVS).…”