Impairment of eyeblink classical conditioning in progressive supranuclear palsy

Abstract

In a previous study we showed that learning in eyeblink classical conditioning (EBCC) is normal in Parkinson's disease (PD) and that the serial reaction time task (SRTT) is only marginally impaired. Since pathological lesions are more widespread in the atypical parkinsonian disorder of progressive supranuclear palsy (PSP) than in PD, we hypothesized that PSP patients may show more profound deficits in the EBCC and SRTT learning tasks. We therefore investigated EBCC with a delay and two trace paradigms, an SRTT and the California Verbal Learning Test (CVLT) in eight patients with PSP and an age-matched control group. In all EBCC paradigms, we found a significant difference between groups with no significant learning in PSP patients. In the SRTT, implicit learning may have been impaired, but verbal and manual sequence recall were only marginally impaired. Verbal memory was significantly worse in PSP patients than in the control group. Our study shows a dissociated pattern of learning abilities in PSP, where the EBCC as a measure of implicit learning is impaired, the explicit sequence detection in the SRTT is relatively preserved, and the verbal memory impaired. We hypothesize that the PSP patients' deficits in EBCC learning may be due to lesions of deep cerebellar nuclei. There may be a clinical role for EBCC in distinguishing PD and PSP patients.

Neural Substrates of Eyeblink Conditioning: Acquisition and Retention

“…Schugens et al (2000) concluded that damage to cerebellar nuclei appears likely in most of these studies. In one study of progressive supranuclear palsy (Sommer et al 2001) where eyeblink conditioning was completely absent, it was concluded that the critical damage was to the cerebellar dentate-interpositus nuclear region.…”

Impairment of brainstem implicit learning paradigms differentiates multiple system atrophy (MSA) from idiopathic Parkinson syndrome

“…The procedures were virtually identical to and detailed in the earlier studies from our group 12 14. In brief, an unconditioned stimulus (UCS), that is, an electric pulse over the supraorbital nerve, invariably induces an eyeblink reflex.…”

“…Electromyographic (EMG) activity was recorded using silver-silverchloride cup electrodes fixed with adhesive tape over the lower eyelid (active electrode) and over the ipsilateral temple (reference electrode); with a sampling rate of 10 kHz 12 14. EMG signals were fed into a recording device and filtered at 100 Hz and 5 kHz (SynAmps, Neuroscan Inc, Virginia, USA).…”

“…Previous studies have shown that learning as measured by EBCC is normal in patients with IPD, but, severely affected in patients with PSP 12 – 14. In contrast to tracking or pointing tasks,15 16 EBCC has the advantage not to depend on manual motor skills.…”

“…In contrast to tracking or pointing tasks,15 16 EBCC has the advantage not to depend on manual motor skills. Learning assessed by the serial reaction time task (SRTT) showed the implicit motor skill close to normal in patients with IPD, whereas patients with PSP were markedly impaired; in contrast, the SRTT sequence recall component as measure of explicit learning was largely preserved in both groups 12 14. We sought to investigate whether implicit learning deficits are specific for PSP or present in MSA as well, thereby comparing the clinical feasibility of SRTT and of EBCC in this patient group.…”