Neuroscience

Brain white matter pathways of resilience to chronic back pain: a multisite validation

Mina Mišić author has email address
Noah Lee
Francesca Zidda
Kyungjin Sohn
Katrin Usai
Martin Löffler
Md Nasir Uddin
Arsalan Farooqi
Giovanni Schifitto
Zhengwu Zhang
Frauke Nees
Paul Geha author has email address
Herta Flor

Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Department of Psychiatry, University of Rochester Medical Center, Rochester, USA
Department of Statistics and Operations Research, University of North Carolina, Chapel Hill, USA
Department of Experimental Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Department of Neurology, University of Rochester Medical Center, Rochester, USA
Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig Holstein, Kiel University, Kiel, Germany

https://doi.org/10.7554/eLife.96312.2

Open access
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Figures and data

A whole brain comparison over the white matter skeleton between SBPr and SBPp patients at baseline and distribution of FA values for each group (New Haven data set).
Results of unpaired t-test (p < 0.05, 10,000 permutations) showing significantly increased FA (fractional anisotropy) in SBPr (recovered) compared to SBPp (persistent) patients within the right superior longitudinal fasciculus (SLF) in the New Haven data set. Rain clouds include boxplots and the FA data distribution for each group depicted on the right side of each boxplot. Jittered circles represent single data points, the middle line represents the median, the hinges of the boxplot the first and third quartiles, and the upper and lower whiskers 1.5*IQR (the interquartile range).

Association between white matter FA values and pain severity (New Haven data set).
Higher fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) are associated with greater pain reduction (from baseline to follow-up) in the New Haven data set.

A whole brain comparison over the white matter skeleton between SBPr and SBPp patients at baseline and distribution of FA values for each group (Mannheim data set).
Results of unpaired t-test (p < 0.05, 10,000 permutations) showing significantly increased FA (fractional anisotropy) in SBPr (recovered) compared to SBPp (persistent) patients at six-months follow-up within the right superior longitudinal fasciculus (SLF) in the Mannheim data set. Rain clouds include boxplots and the FA data distribution for each group depicted on the right side of each boxplot. Jittered circles represent single data points, the middle line represents the median, the hinges of the boxplot the first and third quartiles, and the upper and lower whiskers 1.5*IQR (the interquartile range).

Association between white matter FA values and pain severity (Mannheim data set).
Higher fractional anisotropy (FA) values in the right superior longitudinal fasciculus (SLF) are associated with greater pain reduction (from baseline to follow-up) in the Mannheim data set.

Validation of the accuracy of FA in the right SLF in classifying Mannheim patients.
The right superior longitudinal fasciculus (SLF) cluster from the discovery set accurately classifies patients who recovered (SBPr) and those whose pain persisted (SBPp) in the Mannheim data set at a six-month follow-up. Classification accuracy is based on the ROC curve. Circles on the boxplots represent single data points, the middle line represents the median, the hinges of the boxplot the first and third quartiles, and the upper and lower whiskers 1.5*IQR (the interquartile range). AUC: area under the curve; * p < 0.05.

Validation of the accuracy of FA in the right SLF in classifying Chicago patients.
The right SLF (superior longitudinal fasciculus) cluster from the discovery set accurately classifies patients who recovered (SBPr) and those whose pain persisted (SBPp) in the Chicago (OpenPain) data set at visit 1 (baseline) (A) and visit 2 (one-year follow-up) (B). Classification accuracy is based on the ROC curve. Circles on the boxplots represent single data points, the middle line represents the median, the hinges of the boxplot the first and third quartiles, and the upper and lower whiskers 1.5*IQR (the interquartile range). AUC: area under the curve; * p < 0.05.

Illustration of the right SLF white matter bundles and their FA content in SBPp and SBPr patients of the New Haven data set.
(A) Three-dimensional illustration of SLF tracts connecting the inferior parietal lobe with frontal operculum (left), inferior parietal lobe and middle frontal gyrus (middle), and superior parietal lobe and primary motor cortex (right). Upper two rows show SLF tracts connecting the two regions in 3D with FA values along those tracts shown in blue-to-red. The first row shows two representative SBPr patients and the second row shows 2 representative SBPp patients. (B) Plot of average FA ± SEM along the tracts depicted in A for 15 SBPr and 12 SBPp patients. The histogram plot shows the average number of tracts for these same patient groups. Abbreviations: IPL, inferior parietal lobe; PFO, prefrontal operculum; MFG, middle frontal gyrus; SPL, superior parietal lobe; M1, primary motor cortex.

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