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including the territory of the SCA, but preserved in patients with lesions re-
stricted to the territory of the PICA.
Comparing acquisition of classically conditioned eyeblink responses (CR-
incidence) between patients and sex- and age-matched controls revealed five
main findings. First, the ability to acquire classically conditioned eyeblink re-
sponses was reduced in cerebellar patients (Figure 3A,B). Second, in patients
with unilateral cerebellar lesions conditioning deficits were present ipsilaterally
(Figure 3B). These two results strengthen findings described in the previous
human literature in a larger patient sample with more accurate MR-based de-
scription of the cerebellar lesion. The three other results provide evidence that
some additional findings described in the previous animal literature are transfer-
able to humans. First, deficits of eyeblink conditioning were most prominent in
patients with lesions of the superior cerebellum including hemispheric lobule VI
and/or Crus I. Mean total CR-incidences were most clearly reduced on the af-
fected side compared to the unaffected side in cerebellar patients with lesions
including the territory of the SCA (affected side = 13.0%,
SD
6.31; unaffected
side = 33.9%,
SD
17.7; see filled and open bars in Figure 3D). In cerebellar pa-
tients with lesions restricted to the territory of the PICA, the differences in CR-
incidences comparing the affected and unaffected side were less pronounced
(mean total percentage CR-incidence affected side = 19.0%,
SD
14.3; unaffected
side = 27.6%,
SD
25.7; Figure 3C). Finally, eyeblink conditioning deficits were
not significantly different in patients with pure cortical lesions compared to pa-
tients with additional nuclear impairment nor in patients with unilateral and bi-
lateral lesions. In brief, data indicated that a unilateral cortical lesion within the
superior cerebellum was sufficient to significantly reduce eyeblink conditioning
in humans. Similar to findings in animal models, these areas overlap with re-
gions involved in unconditioned eyeblink control in humans. A recent fMRI
study conducted by our group showed that areas within ipsilateral lobules Crus I
and VI are most active during evocation of the unconditioned eyeblink in
healthy human subjects (18).
In sum, involvement of the human cerebellum in eyeblink conditioning is a
robust finding in various human lesion and functional brain imaging studies de-
spite differences in the cerebellar patients' pathology and differences in the ex-
perimental design. Comparable to the results from eyeblink conditioning studies,
the classically conditioned lower limb withdrawal reflex requires an intact cere-
bellum as well, as has been shown for humans (73) and for animals (40).
2.1.2. Visuomotor Associative Learning
Involvement of the human cerebellum in associative learning does not seem
restricted to conditioning of avoidance reactions. Cerebellar patients have been
shown to be impaired in visual motor associative tasks, which required the link-
