Focal Cortical Atrophy in Cluster Headache Patients

Focal cortical atrophy in cluster headache patients

In order to exclude the possible confounding factor of cortical atrophy on the resting state functional activity we performed a VBM style analysis (Ashburner and Friston 2000; Good et al. 2001)to reveal focal cortical atrophy in cluster headache patients.

Methods

Analysis was carried out by tools of FSL package (Ashburner and Friston 2000; Good et al. 2001; Smith et al. 2004). Non-brain parts were removed from all structural images (Smith 2002), and tissue-type segmentation was carried out by FAST (Zhang et al. 2001). The resulting grey matter partial volume images were registered to a standard space (MNI152) by using linear transformation (Jenkinson and Smith 2001), followed by a non-linear registration (Andersson et al. 2007). The resulting images were averaged to create a study-specific template, to which the native grey matter images were then non-linearly re-registered. The registered partial volume images were next modulated (to correct for local expansion or contraction) by dividing by the Jacobian of the warp field. The modulated segmented images were smoothed with an isotropic Gaussian kernel with a sigma of 3 mm. Finally, the voxelwise General Linear Model (GLM) was applied, using permutation-based non-parametric testing (5000 random permutations). The design matrix was coded for group membership. Thresholding was carried out by threshold-free cluster enhancing technique (TFCE) (Smith and Nichols 2009). Images were thresholded at p<0.05, corrected for multiple comparisons.

Since in CH the headache is strictly unilateral, according to the literature (Absinta et al. 2012; Szabo et al. 2013; Yang et al. 2014), we normalized the data according to the headache side: the images of patients having headache on the left side were inverted along the midsagittal axis by the fslswapdim command (Figure S1). To acknowledge that there are non-pain related differences between the left and right hemispheres we repeated the analysis by inverting the images of the patients who had headache on the right side (not shown). The analysis was also repeated without standardisation (not shown).

Results

Atrophy of the right insular cortex was found in cluster headache patients (p<0.036, corrected, x=-48mm, y=-18mm, z=18mm; Figure S2).

Figure S2. Cortical thinning in CH patients. The results of the VBM analysis are overlayed on the standard MNI152 brain. The colorbar indicates p values.

References

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