The effects of scopolamine on changes in regional cerebral blood flow during classical conditioning of the human eyeblink response

We examined the effects of scopolamine on the functional anatomy of classic al conditioning of the human eyeblink response. Ten healthy young normal fe male volunteers (mean age +/- SEM: 26.7 +/- 0.9 years) were administered 0. 4 mg scopolamine intravenously 1 h before regional cerebral blood flow (rCB F) was measured with positron emission tomography (PET) and (H2O)-O-15. Sca ns occurred during three sequential phases: (1) explicitly unpaired present ations of the unconditioned stimulus (airpuff to the right eye) and conditi oned stimulus (binaural tone), (2) paired presentations of the two stimuli (associative learning) and (3) explicitly unpaired presentation of the stim uli (extinction phase). Scopolamine impaired acquisition of the conditioned eyeblink response (54.7 +/- 4.9%) relative to 18 untreated subjects from t wo previous PET studies. Regions that showed significant relative increases in rCBF during conditioning included the right lateral occipital cortex, t he right inferior occipital cortex, the right lateral temporo-occipital cor tex, the left medial temporo-occipital cortex, the posterior cingulate, the right cerebellum/brain stem area and the medial cerebellum. Significant re lative decreases in rCBF were measured in the thalamus, the left putamen/in sula area, the right putamen and the left and middle cerebellar cortex. The data partially replicate previous findings in unmedicated young volunteers of conditioning-specific rCBF changes in the cingulate cortex, the cerebel lar cortex, the insula and the lateral temporo-occipital cortex. Our findin g of decreased rCBF in the thalamus and increased rCBF in the occipital cor tex may be attributable to effects of scopolamine per se rather than condit ioning. Our data lend further support to the notion that classical conditio ning involves distributed changes in multiple systems within the central ne rvous system.