Dear Caterina,
as you already suggested, I would recommend using 3D files instead of 4D ones. Processing speed will mostly depend on harddisk speed. So, if your external harddisk is much slower than an internal one, rsync'ing files might be a good idea. However, you should be aware that moving files around is only ok for preprocessing. Since SPM stores full paths to data files in its statistics data file SPM.mat, moved files will be a problem for e.g. plotting time courses in statistical analysis.
To keep things simple, I would also suggest to keep the folder structure the same on internal and external harddisk. Then you can simply synchronise the entire project folder. If you use rsync or a similar tool, the overhead of scanning the filesystem for changes will be small.
Best,
Volkmar
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