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Task-based High Angular Resolution Functional Imaging (tHARFI) shows directional contrast of BOLD signal1Vanderbilt University Institute of Imaging Science, Nashville, TN, United States, 2Vanderbilt Brain Institute, Nashville, TN, United States, 3Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United States, 4Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, 5Biomedical Engineering, Vanderbilt University, Nashville, TN, United States, 6Peabody College of Education and Human Development, Nashville, TN, United States, 7BIomedical Engineering, Vanderbilt University, Nashville, TN, United States, 8Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, United States
Synopsis
We present a method to detect and quantify correlated BOLD signals in brain white matter using task-based high angular resolution functional imaging (tHARFI). This technique measures the anisotropic component of these signals, highlighting directional differences between two different task states. The ability to quantify these correlated functional signals in white matter may improve our ability to delineate functional circuits in the brain, and complement other modalities to better understand structural and functional relationships in the brain.
Introduction
We recently introduced high angular resolution functional imaging (HARFI) (1) to describe the local anisotropic correlations of BOLD signals between voxels in the white matter (1-3). The HARFI model is capable of characterizing complex functional orientation distributions (FODs) (Figure 1) that are reminiscent of structural fiber distributions typical of diffusion MRI, which can then be utilized for functional tractography. In this study, we extend the resting-state analysis to task-based analysis, called “tHARFI”, and probe differences in the directionality of BOLD signals between two task-states.Methods
Images were acquired from one subject using a Philips 3T scanner during a standard task-based fMRI protocol (2,3). The subject performed one fMRI run consisting of 3 conditions (repeated twice): Passage reading, Viewing non-alphanumeric symbols, and Fixation. Passage stimuli depicted a story, and were presented one word at a time (as in Aboud et al. (2,3)). The symbolic baseline condition included three non-alphanumeric symbols (two symbol types) displayed horizontally on a slide, and were matched in presentation time to the passage phrases.
We then examined whether there is a difference in anisotropic HARFI correlations between two task states – in this case, we compared “passage” blocks versus “symbols” blocks. To do this, we first calculated the HARFI data for each block (N=2) of symbols and each block of passages using the methodology described in (1). Figure 2 shows the HARFI FODs for a region of interest in the putative visual word form area (pVWFA), where activation is known to occur in the gray matter during written language processing. Finally, we ask “for every voxel, in every direction, where are these functions statistically different between states” by performing a Student’s t-test across the entire FOD (for every direction) for each voxel. Rather than display p-values, we show the t-statistics in order to highlight differences between contrasts.
Results
Figure 3 shows the t-statistics plotted over all directions for the case of “passage > symbols” (i.e., passage minus symbols) and “symbols > passage” for a selected axial slice, and a region of interest near the pVWFA. Here, a bigger value in a given direction means that there is a significantly greater difference between the two tasks in the directional correlation of BOLD signals. Clear patterns, both spatially and orientationally, are observable throughout white and gray matter regions, for both contrasts. For example, white matter adjacent to the VWFA region shows generally less anisotropic correlation in all directions for passage than for symbols.
Figure 4 shows similar maps of t-statistics for an axial slice and highlights tHARFI signals near the inferior frontal gyrus (IFG), another area important during language versus non-alphanumeric symbolic processing. Differences in task-states are apparent in gray matter, for example regions where “passage-symbols” indicates larger local correlations across all directions (white arrows) and similarly for “symbols-passage” (yellow arrow). In addition, white matter shows different directionality based on task states.
Discussion
The tHARFI analysis presents a way to compare the directional correlations of the BOLD signal in white matter tracts across the brain, for multiple task states. Interestingly, these local anisotropic correlations vary significantly between states – in this case, between reading of passages and that of symbols, as previously found for simpler tasks using a tensor analysis by Ding et al. ((4)). These variations show directional components that, importantly, are spatially coherent over large regions. It is interesting that there is also an orientational component of contrast in the gray matter (in addition to white matter).
Unlike conventional task-based analyses, which yield locations of significant differences in BOLD signals, HARFI probes each voxels directional correlation with its neighbors. Thus, tHARFI asks if these directional correlations are greater in certain directions or in different conditions and tasks. Changes in directional preferences as a result of a specific task would intuitively indicate a change within white matter in direct response to a specific functional demand that produces an anisotropic BOLD effect. This would not be readily explained by more global vascular changes that have been postulated to underlie some white matter BOLD effects. Given these findings, it may be informative to cluster groups of voxels with similar HARFI signals (much like that done in resting state fMRI) to identify regions (in both white and gray matter) with similar functional characteristics.
Conclusion
We have presented a way to quantify differences in local anisotropic BOLD signal correlations between two different task states, called tHARFI. While the ultimate significance and potential applications of tHARFI remain to be established, it is clear that there is an orientational component to BOLD signal correlations in white matter, and that these local correlations can differ between different tasks, locations, and orientations.Acknowledgements
This work was supported by the National Institutes of Health under award numbers R01EB017230, and T32EB001628, and in part by ViSE/VICTR VR3029 and the National Center for Research Resources, Grant UL1 RR024975-01.References
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