Adaptive thresholding for reliable topological inference in single subject fMRI analysis

Single subject fMRI has proved to be a useful tool for mapping functional areas in clinical procedures such as tumor resection. Using fMRI data, clinicians assess the risk, plan and execute such procedures based on thresholded statistical maps. However, because current thresholding methods were developed mainly in the context of cognitive neuroscience group studies, most single subject fMRI maps are thresholded manually to satisfy specific criteria related to single subject analyzes. Here, we propose a new adaptive thresholding method which combines Gamma-Gaussian mixture modeling with topological thresholding to improve cluster delineation. In a series of simulations we show that by adapting to the signal and noise properties, the new method performs well in terms of total number of errors but also in terms of the trade-off between false negative and positive cluster error rates. Similarly, simulations show that adaptive thresholding performs better than fixed thresholding in terms of over and underestimation of the true activation border (i.e., higher spatial accuracy). Finally, through simulations and a motor test–retest study on 10 volunteer subjects, we show that adaptive thresholding improves reliability, mainly by accounting for the global signal variance. This in turn increases the likelihood that the true activation pattern can be determined offering an automatic yet flexible way to threshold single subject fMRI maps.

[1]  Satrajit S. Ghosh,et al.  Nipype: A Flexible, Lightweight and Extensible Neuroimaging Data Processing Framework in Python , 2011, Front. Neuroinform..

[2]  Nick F. Ramsey,et al.  Test–retest variability underlying fMRI measurements , 2012, NeuroImage.

[3]  Stephen M Smith,et al.  Fast robust automated brain extraction , 2002, Human brain mapping.

[4]  A. Schleicher,et al.  Two different areas within the primary motor cortex of man , 1996, Nature.

[5]  Dieter Vaitl,et al.  Neuroimaging of emotion: empirical effects of proportional global signal scaling in fMRI data analysis , 2005, NeuroImage.

[6]  M. D’Esposito,et al.  The Inferential Impact of Global Signal Covariates in Functional Neuroimaging Analyses , 1998, NeuroImage.

[7]  Simon B. Eickhoff,et al.  A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data , 2005, NeuroImage.

[8]  Karl J. Friston,et al.  False discovery rate revisited: FDR and topological inference using Gaussian random fields , 2009, NeuroImage.

[9]  Federico E. Turkheimer,et al.  On the logic of hypothesis testing in functional imaging , 2004, European Journal of Nuclear Medicine and Molecular Imaging.

[10]  L. R. Dice Measures of the Amount of Ecologic Association Between Species , 1945 .

[11]  Simon B. Eickhoff,et al.  Testing anatomically specified hypotheses in functional imaging using cytoarchitectonic maps , 2006, NeuroImage.

[12]  R. Felix,et al.  Presurgical functional MRI in patients with brain tumours , 2000, NeuroImage.

[13]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[14]  N V Hartvig,et al.  Spatial mixture modeling of fMRI data , 2000, Human brain mapping.

[15]  Mark W. Woolrich,et al.  Mixture models with adaptive spatial regularization for segmentation with an application to FMRI data , 2005, IEEE Transactions on Medical Imaging.

[16]  Maria Blatow,et al.  Presurgical Functional MRI in Patients with Brain Tumors , 2007 .

[17]  J. Voyvodic Activation mapping as a percentage of local excitation: fMRI stability within scans, between scans and across field strengths. , 2006, Magnetic Resonance Imaging.

[18]  Karl J. Friston,et al.  The Relationship between Global and Local Changes in PET Scans , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  Carl-Fredrik Westin,et al.  fMRI-DTI modeling via landmark distance atlases for prediction and detection of fiber tracts , 2012, NeuroImage.

[20]  Kevin Murphy,et al.  The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? , 2009, NeuroImage.

[21]  Simon B. Eickhoff,et al.  Assignment of functional activations to probabilistic cytoarchitectonic areas revisited , 2007, NeuroImage.

[22]  James T Voyvodic,et al.  Reproducibility of single‐subject fMRI language mapping with AMPLE normalization , 2012, Journal of magnetic resonance imaging : JMRI.

[23]  Stephen M Smith,et al.  Variability in fMRI: A re‐examination of inter‐session differences , 2005, Human brain mapping.

[24]  James T Voyvodic,et al.  fMRI activation mapping as a percentage of local excitation: Consistent presurgical motor maps without threshold adjustment , 2009, Journal of magnetic resonance imaging : JMRI.

[25]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[26]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[27]  B. Everitt,et al.  Mixture model mapping of brain activation in functional magnetic resonance images , 1999, Human brain mapping.

[28]  D. Rubin,et al.  Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper , 1977 .

[29]  David Borsook,et al.  Enhanced false discovery rate using Gaussian mixture models for thresholding fMRI statistical maps , 2009, NeuroImage.

[30]  Gary F. Egan,et al.  Simulation of the Effects of Global Normalization Procedures in Functional MRI , 2002, NeuroImage.