Resolving Human Brain Activation Across Cerebral Cortical Layers with Line-Scan Functional MRI - PROJECT SUMMARY/ABSTRACT Today, functional MRI (fMRI) is the most widely-used method for measuring activity across the entire human brain. FMRI is used to infer ‘functional connectivity’, and most studies utilize coarse spatial resolution (~2 mm isotropic) with which it is possible to detect interactions between brain areas at the centimeter scale. However, this approach lacks the ability to estimate the directionality of neuronal communication flowing from one brain area to another, and thus cannot decipher the underlying circuitry needed to investigate brain computation. Meanwhile, the emerging field of laminar fMRI seeks to resolve activation patterns across cerebral cortical layers, and has shown the potential to interrogate the directionality of these connections by probing correlations between input and output layers of cortical areas. Yet even with the highest spatial resolutions available at 7 Tesla (0.8 mm isotropic), laminar fMRI data are marginally capable of isolating the activity of individual cortical layers and are incapable of covering the entire brain with adequate temporal resolution. Here we propose to supplement conventional whole-brain functional connectivity with an ultra-high spatial resolution (0.125 mm) interrogation of cortical laminar connectivity. Our technology automatically places multiple independent 1D “linescan” fMRI acquisitions normal to the cortical surface within functional ‘hubs’ identified in a prior conventional fMRI scan. Linescan MRI is a classic method that acquires a “1D image”—i.e., a single line—enabling ultra-high spatial resolution in the “in-line” direction down to ~100 μm. Since only one line is encoded, it also enables short readouts and ultra-fast temporal resolution. Linescan MRI is well-suited to cortical layers, provided that the line intersects the cortex exactly perpendicularly. Accurate manual prescription of one linescan at a given location in human cerebral cortex is difficult with the MRI console’s user interface; prescribing several linescans across a brain network is prohibitive. Also, linescans cannot be retrospectively corrected for motion. We will overcome these challenges to enable concurrent linescan fMRI at multiple cortical locations to study communication along feedforward and feedback pathways between cortical areas. We will also develop novel radiofrequency pulses to sharpen the ‘line profiles’ to increase resolution and boost SNR. We will develop both novel gradient-echo linescan fMRI to provide ultra-fast temporal resolution and spin-echo linescan fMRI to provide pure T2 contrast— difficult to attain with conventional fMRI—for microvascular weighting and increased neuronal specificity. We will apply our linescan fMRI in experiments designed to showcase its unique capabilities and advantages. We will extend previous findings by measuring layer-specific interactions between left and right motor cortex, then demonstrate, for the first time, how input layers and the cascade of information across visual cortex can be inferred from the onset time of the layer-specific activation, and test a novel hypothesis about directed communication within the Default Mode Network. The outcomes will be dissemination of data acquisition/analysis technologies that expand the scope of what is possible with fMRI, and novel insights into human brain circuitry.
