Behavioral/Cognitive Cerebellar Cortex and Cerebellar Nuclei Are Concomitantly Activated during Eyeblink Conditioning: A 7T fMRI Study in Humans

There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortexmay be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages.As yet, humanstudies haveprovided little to resolve this question. In thepresent study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased con-comitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p 0.05, permutation corrected). Activations weremost pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations weremost prominent at the first time themaximumnumber of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-sitemodel of learningduring acquisitionof classically conditioned eyeblinks. Because increase