Spurious correlations in surface-based functional brain imaging

Poster No:

1588 

Submission Type:

Abstract Submission 

Authors:

Jayson Jeganathan1, Nikitas Koussis2, Bryan Paton3, Richa Phogat3, James Pang4, Sina Mansour5, Andrew Zalesky6, Michael Breakspear3

Institutions:

1The University of Newcastle, New Lambton Heights, AK, 2University of Newcastle, New Lambton Heights, NSW, 3The University of Newcastle, New Lambton Heights, NSW, 4Monash University, Clayton, Victoria, 5National University of Singapore, Singapore, Singapore, 6The University of Melbourne and Melbourne Health, Melbourne, VIC

First Author:

Jayson Jeganathan  
The University of Newcastle
New Lambton Heights, AK

Co-Author(s):

Nikitas Koussis, PhD  
University of Newcastle
New Lambton Heights, NSW
Bryan Paton, PhD  
The University of Newcastle
New Lambton Heights, NSW
Richa Phogat, PhD  
The University of Newcastle
New Lambton Heights, NSW
James Pang, PhD  
Monash University
Clayton, Victoria
Sina Mansour L., Ph.D.  
National University of Singapore
Singapore, Singapore
Andrew Zalesky, PhD  
The University of Melbourne and Melbourne Health
Melbourne, VIC
Michael Breakspear, PhD  
The University of Newcastle
New Lambton Heights, NSW

Introduction:

The study of functional MRI (fMRI) data is increasingly performed after mapping from volumetric voxels to surface vertices. Processing pipelines commonly used to achieve this mapping produce meshes with uneven vertex spacing. We investigated the causes and impacts of uneven vertex spacing.

Methods:

We used minimally pre-processed resting state fMRI data from the first 20 participants of the Human Connectome Project. Data were represented on the fsLR 32k surface. Statistical tests were corrected for spatial smoothness using the spin test.

Results:

Inter-vertex distances are correlated with sulcal depth, with up to 3 times greater inter-vertex distance in gyri than in sulci (r=0.526, p<0.001) (Figure 1). The bias is propagated from anatomical to empirical fMRI data, where the correlation between adjacent sulcal vertices becomes artefactually inflated due to their proximity (r=-0.508, p<0.001) (Figure 2). Biased nearest-neighbour correlations are present in all participants (one-sample t-test, t(19)=-41.183, p<0.001), on fsLR 32k and fsaverage meshes, with resting and movie-viewing MRI, and with MSMSulc and MSMAll. Biased neighbour correlations do not occur in volume data, demonstrating that the bias arises from surface processing alone (r=0.043, p=0.297). To reproduce the bias in-silico, we generated random Gaussian noise time series independently at each vertex of a participant's uneven surface mesh. Surface smoothing (2mm FWHM) alone yielded artefactually high neighbour correlations in sulcal vertices (r=0.812, p<0.001). We used the in-silico model to explore the consequences of biased neighbour correlations.

First, we found that functional parcellations are biased towards finding parcel boundaries at gyri, even when the underlying data is noise (t(29694)=41.636, p<0.001). Biased parcel boundaries are also seen in commonly used group parcellations (Schaefer et al., 2018) derived from empirical fMRI data (p<0.001). Second, we examined vertex-level fingerprinting accuracy, the ability to match an individual's functional connectome with their own re-test functional connectome. Even when test and re-test data are generated from independent uncorrelated Gaussian noise, individual-specific anatomical cortical folding information leaks into test and re-test functional connectomes, resulting in 98% mean fingerprinting accuracy (chance level 1/20 = 5%).

The onavg template was recently developed to reduce variability in inter-vertex spacing. When the template is projected to individuals' brain surfaces, we find a modest 20.7% reduction in variability. The onavg template abolishes gyral biases in functional parcellation boundaries, but worsens artefactual fMRI fingerprinting.
Supporting Image: new_fig1.png
Supporting Image: new_fig2.png
 

Conclusions:

Surface processing leads to a gyral bias in inter-vertex distances, resulting in gyrally biased fMRI correlations which can adversely impact subsequent analyses. These biases can be partially addressed using the onavg template. The impact of residual biases on one's pipeline can be quantified using surrogate noise data. Surface-based pipelines must be used with caution.

Modeling and Analysis Methods:

Methods Development 2
Motion Correction and Preprocessing 1
Segmentation and Parcellation
Task-Independent and Resting-State Analysis

Keywords:

Statistical Methods
Other - surface; parcellation;

1|2Indicates the priority used for review

Abstract Information

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Please indicate below if your study was a "resting state" or "task-activation” study.

Resting state

Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

Healthy subjects

Was this research conducted in the United States?

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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

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Please indicate which methods were used in your research:

Functional MRI
Structural MRI

For human MRI, what field strength scanner do you use?

3.0T
7T

Which processing packages did you use for your study?

FSL

Provide references using APA citation style.

Schaefer, A., Kong, R., Gordon, E. M., Laumann, T. O., Zuo, X.-N., Holmes, A. J., Eickhoff, S. B., & Yeo, B. T. T. (2018). Local-Global Parcellation of the Human Cerebral Cortex from Intrinsic Functional Connectivity MRI. Cerebral Cortex, 28(9), 3095–3114. https://doi.org/10.1093/cercor/bhx179

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