The spatial resolution of functional magnetic resonance imaging (fMRI) is fundamentally limited by effects from large draining veins. Here we describe an analysis method that provides data-driven estimates of these effects in task-based fMRI. The method involves fitting a one-dimensional manifold that characterizes variation in response timecourses observed in a given dataset, and then using identified early and late timecourses as basis functions for decomposing responses into components related to the microvasculature (capillaries and small venules) and the macrovasculature (large veins), respectively. We show the removal of late components substantially reduces the superficial cortical depth bias of fMRI responses and helps eliminate artifacts in cortical activity maps. This method provides insight into the origins of the fMRI signal and can be used to improve the spatial accuracy of fMRI.
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Materials related to this paper, including all datasets used, are available at https://osf.io/j2wsc/. Raw data in BIDS format63 are hosted at OpenNeuro at https://doi.org/10.18112/openneuro.ds002702.v1.0.1, whereas preprocessed data (that is, temporally and spatially corrected fMRI time-series data in surface format) are provided on the OSF site.
Data were primarily analyzed using custom code written in MATLAB R2018a. The OSF site (https://osf.io/j2wsc/) includes an archive of the code used in this paper, sample data and scripts demonstrating the TDM method, and a link to a detailed video tutorial demonstrating the scripts and discussing the methodology and rationale therein. TDM source code is licensed under the BSD 3-Clause License, and is available at https://github.com/kendrickkay/TDM/ and on the executable platform Code Ocean (https://doi.org/10.24433/CO.4779366.v1)64.
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We thank E. Margalit and N. Petridou for helpful discussions and L. Dowdle for assistance with preparing data in BIDS format. This work was supported by National Institutes of Health grant nos. P41 EB015894 (K.U.), P41 EB027061 (K.U.), P30 NS076408 (K.U.), S10 RR026783 (K.U.), S10 OD017974-01 (K.U.) and U01 EB025144 (K.U.), and the W. M. Keck Foundation (K.U.).
The authors declare no competing interests.
Peer review information Nina Vogt was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Magenta and cyan crosses indicate the early and late timecourses derived from the ICA-based procedure. The ICA-based procedure yields timecourses similar to TDM in some datasets (for example D4), but diverges substantially in others (for example D8).
To facilitate comparison, results obtained using the spin-echo and low-resolution protocols are placed next to results obtained using the high-resolution gradient-echo protocol.
Extended Data Fig. 3 Decomposition of brain activity patterns across datasets and acquisition protocols.
On the left are results obtained using high-resolution (0.8-mm) 7T gradient-echo (Datasets D1–D5). On the right are results obtained using high-resolution (1.05-mm) 7T spin-echo (Datasets D13–D14) and low-resolution (2.4-mm) 3T gradient-echo (Dataset D15–D16). These alternative acquisition protocols were conducted in the same subjects as the high-resolution gradient-echo protocol (correspondence indicated by arrows).
a–c, Results for three surface vertices marked by arrows in Fig. 4. At the upper left are FIR timecourses with ribbon center and width indicating mean and standard error across two condition-splits. Dotted lines indicate the overall fit of the TDM model for each condition (reflecting a weighted sum of the Early and Late timecourses). At the lower left are canonical and TDM-derived timecourses. On the right are the three versions of the betas with bars and error bars indicating mean and standard error across six condition-splits and black arrows indicating peak eccentricity. Rainbow colors indicate stimulus eccentricity (1 = most foveal, 6 = most peripheral).
Extended Data Fig. 5 Response timecourses exhibit diverse proportions of early and late timecourses.
Each subplot depicts results for a single condition at a single vertex (Dataset D1). The left shows FIR timecourses (black, with lines and error bars indicating mean and standard error across two condition-splits) and the overall fit of the TDM model (purple). The right shows beta estimates (bars and error bars indicate mean and standard error across six condition-splits). To select which cases to show, we first identified vertices whose R2 under the TDM GLM is greater than 10%. We then examined the estimated betas and calculated their t-values (beta divided by standard error across condition-splits). We determined (i) all cases with a robust Early beta (t > 5) and a weak Late beta (absolute value less than 1/10 of the Early beta), (ii) all cases with robust Early and Late betas (t > 5) and where each beta is at least 9/10 of the other beta, and (iii) all cases with a robust Late beta (t > 5) and a weak Early beta (absolute value less than 1/10 of the Late beta). Finally, we randomly selected 20 cases from each of the three groups.
a, Histogram. The top plot shows distributions of BOLD amplitudes aggregated across Datasets D1–D12; the bottom plot shows results on a log scale and with a wider x-axis range. b, Kurtosis. Results are shown for individual datasets (thin lines, D1–D12) and the group average (thick black line). c, Standard deviation. d, Cortical depth profiles. The main plot shows the average depth profile observed in Datasets D1–D12, with ribbons indicating standard error across datasets; the inset plots show results for individual datasets (D1–D16), with ribbons indicating standard error across conditions. e, Reliability. Average correlation of betas across 6 splits of each dataset. f, Gradient-echo versus spin-echo. We re-plot results from panels D and E, directly comparing the gradient-echo and spin-echo datasets.
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Kay, K., Jamison, K.W., Zhang, R. et al. A temporal decomposition method for identifying venous effects in task-based fMRI. Nat Methods (2020). https://doi.org/10.1038/s41592-020-0941-6