Atypical multisensory integration in Niemann-Pick type C disease – towards potential biomarkers

Orphanet Journal of Rare Diseases

John J Foxe¹  Steven U Walkley¹  Alice B Brandwein⁴  John S Butler³  Sophie Molholm¹  Gizely N Andrade² 

[1] The Dominick P. Purpura Department of Neuroscience, Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, Albert Einstein College of Medicine, Bronx 10461, NY, USA;Program in Cognitive Neuroscience, The Graduate Center of the City University of New York, 365 Fifth Avenue, New York 10016, NY, USA;Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland;Department of Pediatrics, The Sheryl and Daniel R. Tishman Cognitive Neurophysiology Laboratory, Children¿s Evaluation and Rehabilitation Center (CERC), Albert Einstein College of Medicine & Montefiore Medical Center, Van Etten Building ¿ Wing 1C, 1225 Morris Park Avenue, Bronx 10461, NY, USA

关键词: Sensory integration;    Audio-visual;    Sensory processing;    Rare disease;    Cross-modal;    Lysosomal disease;    NPC2;    NPC1;    Neurodegeneration;    Race model;   

Others  :  1149699
DOI  :  10.1186/s13023-014-0149-x

 received in 2014-03-17, accepted in 2014-09-16,  发布年份 2014

【 摘 要 】

Background

Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the respective sensory cortices (e.g. the auditory and visual systems).

Methods

A simple way to test integrity of the multisensory system is to ask whether individuals respond faster to the occurrence of a bisensory event than they do to the occurrence of either of the unisensory constituents alone. Here, we presented simple auditory, visual, and audio-visual stimuli in random sequence. Participants responded as fast as possible with a button push. One 11-year-old and two 14-year-old boys with NPC participated in the experiment and their results were compared to those of 35 age-matched neurotypical boys.

Results

Reaction times (RTs) to the stimuli when presented simultaneously were significantly faster than when they were presented alone in the neurotypical children, a facilitation that could not be accounted for by probability summation, as evidenced by violation of the so-called `race¿ model. In stark contrast, the NPC boys showed no such speeding, despite the fact that their unisensory RTs fell within the distribution of RTs observed in the neurotypicals.

Conclusions

These results uncover a previously undescribed deficit in multisensory integrative abilities in NPC, with implications for ongoing treatment of the clinical symptoms of these children. They also suggest that multisensory processes may represent a good candidate biomarker against which to test the efficacy of therapeutic interventions.

【 授权许可】

   
2014 Andrade et al.; licensee BioMed Central Ltd.

【 图 表 】

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