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.

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

“…Likewise, human cerebellar lesion studies show that lobule VI and Crus I are important in acquisition of conditioned eyeblink responses (Gerwig et al, 2003). As in the present study, most PET and fMRI studies in healthy human subjects show more extended areas of activation bilaterally including also parts of the anterior lobe, lobule VIIB and lobule VIII (Blaxton et al, 1996;Cheng et al, 2014). A more extended cerebellar network appears to be involved in acquisition of conditioned eyeblink responses, although only lesions of lobule VI and adjacent Crus I ipsilateral to the US are followed by significant reduction of learning ability.…”

“…Miller et al (2003) found an acquisition-related fMRI signal decrease in bilateral lobule VI in rabbits. Previous positron emission tomography (PET) studies in humans showed both increases of regional cerebral blood flow (rCBF; Blaxton et al, 1996;Parker et al, 2012) and glucose metabolism (Logan and Grafton, 1995), as well as decreases of rCBF (Molchan et al, 1994;Schreurs et al, 1997Schreurs et al, , 2001Parker et al, 2012). Based on the present findings the assessment time during the course of learning is crucial.…”

Learning about pain: The neural substrate of the prediction error for aversive events

“…Indirect demonstrations of hippocampal involvement in this type of mismatch come from single-cell recording (32) and from functional brain imaging during pseudoconditioning (33). This involvement suggests that the hippocampus is engaged when there is no sensory stimulation but memories relevant to the context are at variance with this experience.…”

Cerebellum volume and eyeblink conditioning in schizophrenia

“…Other studies have implicated the posterior cerebellar cortex in CR acquisition, but with a limited role in the timing of the CR (e.g., Attwell, Rahman, and Yeo, 2001). These findings in rabbits have been supported in humans using positron emission tomography (Logan and Grafton, 1995;Blaxton et al, 1996) and functional MRI (Ramnani et al, 2000;Dimitrova et al, 2002). Clinically, insults to the cerebellum have been shown to markedly impair acquisition of the conditioned eyeblink response (Daum et al, 1993;Woodruff-Pak et al, 1996).…”