Functional MRI of cerebellar activity during eyeblink classical conditioning in children and adults

Abstract

This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I-II, lateral lobules IV-IX, and vermis IV-VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC.

Keywords: cerebellum; development; learning; memory; neuroimaging.

Figure 1

Study design/analysis and sample topography of eyeblink responses measured in the MRI scanner. (A) Pseudoconditioning consisted of alternating four delay tone alone and four airpuff alone blocks. Conditioning sessions consisted of eight blocks of paired CS‐US trials. Adults received three separate sessions (1 pseudoconditioning + 2 conditioning) and children received five separate sessions (1 pseudoconditioning + 4 conditioning). (B) Typical response profiles are shown for non‐CR and CR trials. Peak amplitude responses indicate maximal eye closure. (C) Dotted lines indicate the time window from which eyeblink responses were sampled.

Figure 2

Behavioral findings in children and adults. A significantly greater percentage of CRs was exhibited during conditioning relative to pseudoconditioning, indicating that both groups learned the CS‐US association. Between session contrasts: % CRs in each session labeled “b” was significantly greater (at P < 0.05) than during pseudoconditioning, which is labeled “a.” Between group contrasts: adults produced significantly more CRs than children during sessions 1 and 2 (**P < 0.01; *P < 0.05).

Figure 3

Whole cerebellum analyses showing regions with significantly greater responses during session 1 of conditioning relative to pseudoconditioning in children.

Figure 4

Whole cerebellum analyses showing regions with significantly greater response in children relative to adults during session 1 of conditioning (minus pseudoconditioning).

Figure 5

Relation of mean activation in left cerebellar deep nuclei to CRs in children. Left panel shows that activity in the left cerebellar deep nuclei was positively correlated with CRs in session 1. Smaller graphs on the right show this region separated into dentate, fastigial, and interposed nuclei and show that session 1 activity within these subnuclei also correlated with CRs.

Figure 6

Relation of mean activation in vermis to CRs in children. Activity in the vermis was positively correlated with CRs in sessions 1 and 2.