Early fMRI responses to somatosensory and optogenetic stimulation reflect neural information flow

Abstract

Blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (fMRI) has been widely used to localize brain functions. To further advance understanding of brain functions, it is critical to understand the direction of information flow, such as thalamocortical versus corticothalamic projections. For this work, we performed ultrahigh spatiotemporal resolution fMRI at 15.2 T of the mouse somatosensory network during forepaw somatosensory stimulation and optogenetic stimulation of the primary motor cortex (M1). Somatosensory stimulation induced the earliest BOLD response in the ventral posterolateral nucleus (VPL), followed by the primary somatosensory cortex (S1) and then M1 and posterior thalamic nucleus. Optogenetic stimulation of excitatory neurons in M1 induced the earliest BOLD response in M1, followed by S1 and then VPL. Within S1, the middle cortical layers responded to somatosensory stimulation earlier than the upper or lower layers, whereas the upper cortical layers responded earlier than the other two layers to optogenetic stimulation in M1. The order of early BOLD responses was consistent with the canonical understanding of somatosensory network connections and cannot be explained by regional variabilities in the hemodynamic response functions measured using hypercapnic stimulation. Our data demonstrate that early BOLD responses reflect the information flow in the mouse somatosensory network, suggesting that high-field fMRI can be used for systems-level network analyses.

Simulating Local Deformations in the Human Cortex Due to Blood Flow-Induced Changes in Mechanical Tissue Properties: Impact on Functional Magnetic Resonance Imaging

“…For example, we found a factor of 3 higher displacement when activating one central layer instead of layer 1. As neuronal activity is usually distributed across several layers in most fMRI paradigms, the activated tissue volume will probably be even higher while the highly vascularized and perfused central layers are expected to dominate local tissue displacement effects ( Shen et al, 2008 ; Jung et al, 2021 ). We found that the relative displacement effect (normalized by the volume of the activated layer segment) slightly decreases from outer to inner layers.…”

Dissection of brain-wide spontaneous and functional somatosensory circuits by fMRI with optogenetic silencing

“…To calculate group-averaged fMRI maps, a study-specific mouse brain template was constructed from CBV-weighted fMRI images based on a previously used pipeline (45, 46), as follows. First, the brain area was semiautomatically extracted from the temporal average of all fMRI images for each animal, and intensity nonuniformity was corrected with bias field estimation.…”

“…The fMRI response maps for individual animals were generated using preprocessing and general linear model (GLM) analysis. The steps of preprocessing were previously described in detail (30, 45). In short, preprocessing included slice timing correction, image realignment for minor head motions, linear signal detrending for signal drift removal, and time course normalization by the average of the baseline period.…”

“…where 0 is the signal at TE = 0 ms. For quantification of tissue 2 * changes, the ROI was defined as a 2D sphere with a radius of 500 μm centered on the anatomical location of S1FL with reference to the Allen mouse brain atlas. To calculate group-averaged fMRI maps, a study-specific mouse brain template was constructed from CBV-weighted fMRI images based on a previously used pipeline (45,46), as follows. First, the brain area was semiautomatically extracted from the temporal average of all fMRI images for each animal, and intensity nonuniformity was corrected with bias field estimation.…”

Emerging imaging methods to study whole-brain function in rodent models

“…Being able to use high spatiotemporal resolution is also critical to discern the direction of information flow using the onset times of fMRI responses. For example, Jung and colleagues [ 72 ] applied a GRE-EPI sequence at an ultra-high magnetic field (15.2 T) with a temporal resolution of 250 ms and spatial resolution of 156 × 156 × 500 μm 3 during either electrical paw stimulation or optogenetics stimulation of the motor cortex. Their results showed that the order of onset times varies between regions and active layers and coincides with their known sequence of neural activation.…”