dataset.zip

Literature search and inclusion

A
comprehensive and systematic search was performed in PubMed and ScienceDirect
Database (from January 1999 to June 2016) for VBM studies of IGE，
by using the following keywords: “gray matter” AND (“epilepsy” OR “JME” OR “juvenile
myoclonic epilepsy” OR “GTCS” OR “generalized tonic-clonic seizure” OR “AE” OR “childhood
or juvenile absence epilepsy” OR “IGE” OR “idiopathic generalized epilepsy”)
AND (“Voxel-based morphometry” OR “VBM” OR “Voxel-wise”). For the studies
obtained, each was respectively scanned by a professor who specializes in
neuroimaging and an experienced neurologist, to determine if it met the
inclusion criteria. The references in the selected studies were also reviewed
to identify the relevant papers.

The
included studies should meet these criteria: (1) full text is accessible and
published in English with peer review; (2) reporting a VBM comparison on gray
matter volume between IGE patients and healthy controls; (3) reporting the
stereotactic coordinates of significant GMV abnormalities across the whole
brain; (4) corrected significance levels for multiple comparisons, or uncorrected
levels with spatial extent thresholds were used.

A
study was eliminated if (1) there was no healthy control group; (2) this study
were not reported on Talairach or Montreal Neurological Institute (MNI)
stereotactic coordination; (3) the data overlapped with other articles; (4) the
reported changes were uncorrected and the spatial extent threshold was not
reported; (5) the patients were infants or newborns; (6) the subject information
was insufficient. The method used in the present study was according to the
Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for
observational studies[18].

ALE meta-analysis

For
comparing the GMV difference and seeking a consistent anatomical bias among IGE
subsyndromes, we used BrainMap database (http://www.brainmap.org/),
which is an online database of structural neuroimaging studies in the form of
stereotactic(x,y,z) coordinates, including most of the published VBM studies
(most papers included in our study can be found in this database). Thus, the
above collected VBM studies, if included in this database, were firstly
retrieved, and the associated information and coordinates were extracted from
the Brainmap database using the tool Sleuth 2.3.6 (http://www.brainmap.org/). Experiments
unavailable in the database were manually encoded using Scribe 2.3.1 (http://www.brainmap.org/). Coordinates
in Talairach & Tournoux (T&T) space were converted to Montreal
Neurological Institute (MNI-152) space by using the icbm2tal transform in ALE.

        In this study, we performed pooled analysis to
compare the difference of GMV abnormalities between IGE and controls, and
within-subtypes analysis to compare the difference of GMV abnormalities between
JME and controls, or AE and controls, by using cluster-level thresholding of
ALE algorithm. When using cluster level inference, the simulated data are
thresholded by using a “cluster-forming threshold”. GingerALE finds the
contiguous volumes of clusters above the threshold, and then tracks the
distribution of their volumes by using permutation threshold. False
discovery rate (FDR)-corrected threshold inference was used to control the rate
of false positive. In this study, pooled and within-subtypes analysis was
performed by using a cluster level threshold of 0.05, a permutation threshold
of 1000, and a FDR-corrected P value of less than 0.05. Notably, we did not
perform meta-analysis for GTCS, since there were very few studies (1 for GMV
increase, 2 for GMV decrease) about this subtype.

       For comparing the difference of GMV
abnormalities between JME and AE, we made a contrast analysis for these two
subtypes. In this between-subtypes contrast analysis, GingerALE created
simulated data by pooling the foci datasets and randomly dividing them into two
new groups, which had the same size as the input data sets. For example, JME
contained 20 foci, while AE consisted of 29 foci, then the pooled data of 49
foci were therefore randomly divided into two groups, one 20 and the other 29
foci. ALE values were calculated for each group, and then compared to the ALE
values of the true data. After 1000 permutations, a null distribution was
generated for the difference in ALE values between JME and AE. The true difference
in ALE values was then tested against this null hypothesis at each voxel,
generating a voxel-wise P-value image that was thresholded with a FDR <0.05
and a minimum cluster size of 100 mm3.

In
addition, conjunction analysis was carried out for JME and AE to assess the
common regions with GMV abnormalities. This was derived from the voxel-wise
minimum value of the input ALE images. The resulting conjunction image reflects
the statistically significant similarities between the JME and AE.

Mango
software (http://ric.uthscsa.edu/mango)
was employed to visualize the ALE results, which were overlaid on the MNI-152
brain template in MNI coordinate space.