Objective: To investigate whether Voxel based morphometry (VBM) can also detect acute changes induced by a simple checkerboard paradigm. Background Previous studies used VBM for imaging long term alteration within the gray matter of the brain. Increased and decreased densities were reported after special tasks or conditions such as learning to juggle. Acute changes of cerebral activation have been only studied by functional imaging. Design/Methods: Twenty healthy subjects were investigated using VBM. Three MRIs were applied to each single subject: one before looking at a flickering checkerboard, one right after looking at the checkerboard and one 1 hour later. For each subject a map of grey matter volumetric differences between the scans of different time points was calculated. After within processing all scans of one time point were aligned together and normalized (Dartel algorithm of SPM 8, Matlab 7). As control experiment we performed regular fMRI with checkerboard stimulation in all participants. Results: Changes within the occipital lobe were detected, most pronounced right after application of the flickering checkerboard. Changes almost entirely disappeared within one hour. The same region showed activation in a regular fMRI block design using the checkerboard. Conclusions: The observed changes appear to be generated by looking at the checkerboard as they occur in the occipital lobe which is known to be activated in visual paradigms of multitudinous previous fMRI and PET studies. Up to now, VBM changes were interpreted as either neuronal growing/degeneration, or dendrite spine and synapse turnover, or changes of the extracellular space/ microvascular volume. In contrast to long term VBM alterations, acute VBM changes rather seem to reflect actions that must occur much faster than the suggested, for instance water displacement. This phenomenon might explain the wide diversity of results by different VBM studies not controlling for acute changes or using cross sectional design. Disclosure: Dr. Holle has nothing to disclose. Dr. Naegel has nothing to disclose. Dr. Hagenacker has nothing to disclose. Dr. Theysohn has nothing to disclose. Dr. Diener has received personal compensation for activities with Merck, Pharm Allergan GmbH, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Coherex Medical, CoLucid, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, and Grenenthal.Dr. Diener has received research support from Merck, Pharm Allergan GmbH, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, Coherex Medical, CoLucid, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Grenenthal, Janssen Pharmaceuticals. Dr. Katsarava has received personal compensation for activities with Allergan, Inc. as a consultant. Dr. Obermann has received research support from the German Federal Ministry of Education and Research.