Cerebellar-dependent associative learning is preserved in Duchenne muscular dystrophy: a study using delay eyeblink conditioning.

Ulrike Schara,Dagmar Timmann,Marcus Gerwig,Melanie Busse,Atsushi Asakura

doi:10.1371/journal.pone.0126528

Ulrike Schara, Dagmar Timmann + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0126528

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Journal: PloS one	Publication Date: May 14, 2015
Citations: 9	License type: CC BY 4.0

Affiliation: University of Duisburg-Essen

Abstract

ObjectiveBesides progressive muscle weakness cognitive deficits have been reported in patients with Duchenne muscular dystrophy (DMD). Cerebellar dysfunction has been proposed to explain cognitive deficits at least in part. In animal models of DMD disturbed Purkinje cell function has been shown following loss of dystrophin. Furthermore there is increasing evidence that the lateral cerebellum contributes to cognitive processing. In the present study cerebellar-dependent delay eyeblink conditioning, a form of associative learning, was used to assess cerebellar function in DMD children.MethodsDelay eyeblink conditioning was examined in eight genetically defined male patients with DMD and in ten age-matched control subjects. Acquisition, timing and extinction of conditioned eyeblink responses (CR) were assessed during a single conditioning session.ResultsBoth groups showed a significant increase of CRs during the course of learning (block effect p < 0.001). CR acquisition was not impaired in DMD patients (mean total CR incidence 37.4 ± 17.6%) as compared to control subjects (36.2 ± 17.3%; group effect p = 0.89; group by block effect p = 0.38; ANOVA with repeated measures). In addition, CR timing and extinction was not different from controls.ConclusionsDelay eyeblink conditioning was preserved in the present DMD patients. Because eyeblink conditioning depends on the integrity of the intermediate cerebellum, this older part of the cerebellum may be relatively preserved in DMD. The present findings agree with animal model data showing that the newer, lateral cerebellum is primarily affected in DMD.

Highlights

Duchenne muscular dystrophy (DMD) is a monogenetic X-chromosome linked recessive disorder with mutations of the dystrophin gene, resulting in a deficient and lowered dystrophin protein [1]
conditioned eyeblink responses (CR) acquisition was not impaired in DMD patients as compared to control subjects (36.2 ± 17.3%; group effect p = 0.89; group by block effect p = 0.38; ANOVA with repeated measures)
Delay eyeblink conditioning was preserved in the present DMD patients

Summary

Introduction

Duchenne muscular dystrophy (DMD) is a monogenetic X-chromosome linked recessive disorder with mutations of the dystrophin gene, resulting in a deficient and lowered dystrophin protein [1]. Cognitive deficits and speech disturbances in DMD patients have been described already in early reports [4]. More recent data suggest that patients show impaired problem solving, planning and other disturbed higher cognitive and executive functions [5]. Deficits in attention in verbal tasks, sentence repetition and recall of digits, phonological processing and verbal working memory have been reported [6,7,8,9]. In animals lack of dystrophin was followed by impaired long term object recognition and spatial memory [10]. For a detailed recent review of neuropsychological and neurobehavioral findings in DMD patients the reader is referred to Snow et al [11]

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Conclusion