Functional mapping of human learning: a positron emission tomography activation study of eyeblink conditioning

Abstract

Regional cerebral blood flow (rCBF) was measured using positron emission tomography during eyeblink conditioning in young adults. Subjects were scanned in three experimental conditions: delay conditioning, in which binaural tones preceded air puffs to the right eye by 400 msec; pseudoconditioning, in which presentations of tone and air puff stimuli were not correlated in time; and fixation rest, which served as a baseline control. Compared with fixation, pseudoconditioning produced rCBF increases in frontal and temporal cortex, basal ganglia, left hippocampal formation, and pons. Learning-specific activations were observed in conditioning as compared with pseudoconditioning in bilateral frontal cortex, left thalamus, right medial hippocampal formation, left lingual gyrus, pons, and bilateral cerebellum; decreases in rCBF were observed for bilateral temporal cortex, and in the right hemisphere in putamen, cerebellum, and the lateral aspect of hippocampal formation. Blood flow increased as the level of learning increased in the left hemisphere in caudate, hippocampal formation, fusiform gyrus, and cerebellum, and in right temporal cortex and pons. In contrast, activation in left frontal cortex decreased as learning increased. These functional imaging results implicate many of the same structures identified by previous lesion and recording studies of eyeblink conditioning in animals and humans and suggest that the same brain regions in animals and humans mediate multiple forms of associative learning that give meaning to a previously neutral stimulus.

Fig. 1.

Illustration of experimental paradigm. The order of scans encountered in the study are shown on the left, and stimulus events for pseudoconditioning and conditioning scans are shown on the right. During delay conditioning scans (4–7), 500 msec binaural tones preceded 3–5 psi air puffs to the right eye by 400 msec with an average ITI of 10 sec.

Fig. 2.

Behavioral data. The top left portion of the figure illustrates a CR recorded during conditioning, whereas the bottom left tracings obtained during pseudoconditioning show the absence of an eyeblink response to the binaural tone (single-line stimulus) and an eyeblink after presentation of the air puff alone (double-line stimulus). The learning curve measured across conditioning trials is presented on the right, showing that the proportion of CRs produced increased over the blocks of trials in the experiment.

Fig. 3.

Images of change significance for the three planned comparisons at three different axial levels (low, midline, and high) sampled in the experiment. Activations are shown inred and deactivations in blue. The left column shows a plane sampled from 24 mm below the AC–PC line, themiddle column shows results from the plane positioned on this line (0 mm), and the right column shows images obtained from a plane 24 mm above this line.

Fig. 4.

Changes in activation across conditioning trials for regions in left frontal cortex, left hippocampal formation, and cerebellum. Activation in cerebellum and left hippocampal formation increased as learning trials progressed, but the left frontal cortex showed the opposite trend, actually becoming less activated as the CS–US association was learned.