Evaluation of multiple-session eyeblink conditioning comparing patients with focal cerebellar lesions and cerebellar degeneration

Introduction: Superior parts of the cerebellum have been shown to be critically involved in eyeblink conditioning. The cerebellar function in associative learning has been related to acquisition, but also appropriate timing of conditioned responses (CRs). The aim of the present study was to analyze incidences and timing of CRs across three conditioning sessions on three consecutive days.

Methods: A standard delay paradigm (a 540ms tone coterminating with a 100ms air-puff) was used in 9 patients with pure cortical cerebellar degeneration, 13 patients with focal ischemic cerebellar lesions, and 13 controls. Focal lesions were restricted to the cerebellar cortex. Conditioning was performed on one side, i.e. on the affected side in focal patients and on the right side in patients with degenerative disorders and controls. The affected cerebellar lobules were determined by 3D magnetic resonance imaging (MRI) in patients with focal lesions. To assess the degree of atrophy volumetric measurements of the cerebellum and its major subdivisions were done in patients with degenerative disorders.

Results: There was an increase of CR incidences on day 1 in patients with focal lesions. Mean CR incidences were significantly lower than in controls, no further improvement was visible on days 2 and 3. In patients with degenerative disorders CR incidences were significantly reduced. No clear increase could be observed across the three days. Analysis of timing showed that CRs occurred earlier in cerebellar patients. Shortened latencies were most pronounced in patients with degenerative disorders. On day 3 mean values for CR-onset and peak time in patients with focal lesions had improved close to values of the controls.

Conclusion: CR acquisition and timing were severely affected in patients with degenerative compared to focal cerebellar lesions. Most likely some of the cerebellar areas involved in eyeblink conditioning were preserved in focal patients. More importantly findings suggest that both degenerative and focal cerebellar lesions produce permanent deficits in the acquisition of CRs. No recovery of CR acquisition was observed in multiple sessions. In patients with focal cerebellar lesions, but not with degenerative disease, some recovery of disordered timing function was found. A possible reason may be that the anterior lobe, which is known to be involved in CR timing, was preserved in the majority of focal cerebellar patients.

Supported by the Bernd Fink Foundation