Trace eyeblink conditioning in human subjects with focal cerebellar lesions

Introduction: Delay eyeblink conditioning, a model for associative motor learning in which the conditioned stimulus (CS) overlaps and coterminates with the unconditioned stimulus (US), has been shown to be dependent on the cerebellum. The more complex trace eyeblink conditioning is characterized by a stimulus-free trace interval that separates the CS and the US. It has been shown to be reduced following hippocampal lesions in animals and humans. Animal lesion studies suggest that cerebellar structures may be equally involved in trace eyeblink conditioning and may provide the essential stimulus response association. In humans, trace eyeblink conditioning has been assessed only in one cerebellar case study.

Methods: Trace eyeblink conditioning was investigated in 31 patients with focal cerebellar lesions and 19 age-matched controls. 12 patients presented with lesions including the territory of the superior cerebellar artery (SCA patients) and 19 patients with lesions within the territory of the posterior inferior cerebellar artery (PICA patients). In each patient the extent of the cortical lesion and possible involvement of cerebellar nuclei was determined by 3D MR imaging. Eyeblink conditioning was performed using a tone (2 KHz, duration 40 ms, 70 dB SPL) as conditioned stimulus (CS) followed by a stimulus free trace-interval of 400 ms and a 100 ms air-puff serving as unconditioned stimulus (US).

Results: CR-incidences tended to be reduced on the affected side in cerebellar patients compared with the matched side in controls. The difference was not significant and less compared with previous findings in delay eyeblink conditioning. No significant side differences were found comparing the affected and unaffected side in all cerebellar patients, in PICA patients and in the group of all SCA patients. Compared with SCA patients with pure cortical lesions CR-incidences were significantly decreased in SCA patients with involvement of interposed nuclei, independent of previous experience with delay conditioning.

Conclusions: Cerebellar patients appeared to be less affected in trace compared with delay eyeblink conditioning. A significant impairment was observed in the patients with lesions of the superior cerebellum including at least parts of the interposed nuclei. Findings suggest that extracerebellar areas may contribute significantly to learning in trace eyeblink conditioning and may compensate effects of cerebellar lesions in humans.