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hi christian we struggled with the same problem, since we had one rare subject that we wanted to compare to a group of controls. Our approach was first to do 2-sample t-tests in spm, and then to validate our findings through further analysis; in our case we additionally calculated non-parametric permutation tests with SnPM which confirmed/added additional evidence significant activity changes in our subject of interest. Furthermore we also extracted mean activity values from ROI's in the subject of interest and compared them to each individual of the control group, setting a threshold (+/- 1.5 s.d. or 2 s.d. or any value that is requested for your specific kind of questions). You may have a look at our publication to get a better idea: Mondadori et al., Brain, 129, 2908-2922. best regards christian ----- Original Message ----- From: Christian Keysers To: [log in to unmask] Sent: Wednesday, April 18, 2007 10:48 AM Subject: [SPM] 2 sample t-test of 2 patients against 16 controls Dear SPM mailing list, we have conducted a study comparing 2 rare patients against 16 controls. We have the same contrast (lets call it C) in all 18 subjects at the first level. At the second level I performed a 2-sample t-test (voxelwise) with 2 subjects in group 1 and 16 subjects in group 2. One of the reviewers states: Regarding the 2 sample t-test. I wonder if SPM2 is able to compare 2 subjects versus 16. I believe this is not the case and that one must use a different methodology to make this comparison. I would like to see a citation to a study that uses a similar approach that might alleviate this concern. Is anyone aware of other studies using a similar approach, or a comment from the makers of SPM regarding this issue? ck -- * * *Prof Christian Keysers, PhD *Scientific director neuroimaging center Professor for the neural basis of empathy http://www.bcn-nic.nl/index_research_empathy.html University Medical Center Groningen, University of Groningen A. Deusinglaan 2, 9713AW Groningen, The Netherlands Phone: +31 50 3638794, Fax: +31 50 3638875