The development of visual- and auditory processing in Rett syndrome: An ERP study

Abstract

Rett syndrome is a neurodevelopmental disorder that occurs almost exclusively in females. It is characterized by a progressive loss of intellectual functioning and motor skills, and the development of stereotypic hand movements, that occur after a period of normal development. Event-related potentials were recorded to a passive auditory- and visual oddball task in 17 females with Rett syndrome aged between 2 and 60 years, and age-matched controls. Overall the participants with Rett syndrome had longer ERP latencies and smaller ERP amplitudes than the Control group suggesting slowed information processing and reduced brain activation. The Rett groups also failed to show typical developmental changes in event-related brain activity and revealed a marked decline in ERP task modulation with increasing age.

Introduction

Rett syndrome is characterized by regression of language and psychomotor development at a certain age period, autistic behavior, dementia, seizures, and the loss of purposeful use of the hands [1], [2], [3]. Features like breathing dysfunction, electroencephalographic abnormalities, spasticity, peripheral vasomotor disturbance, scoliosis, and growth retardation are common in Rett syndrome, although not all persons with Rett share these features to the same extent [4]. The syndrome occurs almost exclusively in females and has a prevalence of 1 in 10–15,000 live born girls [5]. With the present clinical knowledge and molecular diagnosis the incidence is probably much higher. Rett syndrome is usually sporadic and only 1% of the reported cases are familial. In most cases, Rett syndrome is caused by mutations in MECP2, the gene encodes the X-linked methyl-CpG-binding protein 2 (MeCP2) located at Xq28 [6], [7].

In recording electrical brain activity during task performance it is possible to extract event-related potentials (ERPs) that are manifestations of brain activities that occur in preparation for, or in response to, discrete events that can be internal or external to the subject [8]. An ERP consists of amplitude changes over time characterized by a characteristic polarity (positive ‘P’ or negative ‘N’ peaks), latency, and scalp distribution. The timing of a cognitive process modulated by a certain task can be inferred from the latency of the corresponding peak, and the amplitude of the peak refers to the degree of activation or strength of the process [9].

An early ERP component like the ‘P1’ reflects visual encoding and decreases in amplitude with age during childhood [10]. The later occuring ‘Novelty P3’ is elicited by unexpected novel stimuli and is thought to reflect involuntary switching of attention to deviant events [11]. In children the Novelty ERP is characterized by a negative ‘Nc’ wave and a positive ‘Pc’ wave. The transition from the childhood Nc/Pc complex to the adult Novelty P3 is not ‘complete’ until after the mid-teens [12], [13].

To date only two reports addressed information processing in Rett syndrome using ERPs. In using auditory- and visual evoked potential paradigms Bader et al. [14] reported P3 activity in nine girls with Rett suggesting remaining perceptual and discrimination properties. McCulloch et al. [15] investigated 11 girls and young women (age range 5–24 years) with Rett syndrome of which three subjects participated in a ‘face discrimination paradigm’, and four subjects in a ‘face recognition paradigm’. Unlike the study by Bader et al. [14] they were not able to identify any ERP components in their Rett participants.

Other developmental disorders have been studied more extensively with ERPs. Ikeda et al. [16] examined a group of mentally retarded adults and controls with an auditory oddball task. They found a dysfunction of automatic auditory processing in mentally retarded persons but the Novelty P3 was similar in both groups. Courchesne found that the Nc response is entirely absent or strikingly aberrant in infantile autism [13]. Karrer et al. [17] studied 6-month-old infants with Down syndrome during a visual recognition memory task. They found that infants with Down syndrome had larger Nc amplitudes as compared to infants without Down syndrome [18]. In adults with Prader–Willi syndrome (PWS) and normal controls ERPs were recorded to a visual- and auditory oddball task [19]. The PWS group revealed an abnormal deflation of the P3 component to the visual, and even to a larger extent to the auditory oddball task.

The present ERP study presents a life span approach to study the development of auditory- and visual processing using passive oddball paradigms in 2- to 60-year-old females with Rett syndrome and age-matched controls.