Endocrine Abstracts

Background

Prader Willi syndrome (PWS) is a genetic disorder with a broad clinical expression. Severe hypotonia with feeding difficulties during early infancy and delayed motor development are very characteristic. At older ages, common motor features in the PWS phenotype include decreased muscle strength, deficiencies in motor coordination and sequencing, gait disturbances and dyspraxic manifestations, with no clear pathophysiological mechanism yet identified. The motor symptoms in PWS may be, in part, the result of the same alteration(s) in the brain system involved in motor control.

Objective

We aimed to examine the brain’s motor system in PWS using functional magnetic resonance imaging (fMRI) with motor activation paradigms.

Methods

Twenty-three adults with PWS (12 women, age mean ± SD, 30.6 ± 10.1 years) participated in the study. Twenty-three age- and sex-matched healthy participants served as a control group. fMRI testing involved the performance of three manual tasks of different motor complexity: (i) repetitive flexion-extension of one hand; (ii) bimanual anti-phase repetitive flexion-extension movements; and (iii) repetitive sequence of fingers-to-thumb opposition with the right hand. Behavioral measurements of overall motor function were also registered by evaluating hand grip strength using a Jamar dynamometer, functional mobility and risk for falls as assessed by the Timed Get Up and Go (tGUG) test, and a quantitative measure of balance using the Berg balance scale. Whole-brain activation maps were compared between groups and correlated with behavioral measurements.

Results

As expected, participants with PWS showed significantly lower scores than controls on all the behavioral measures of motor function. Performance of the motor tasks engaged cortical and subcortical neural elements typically involved in motor processing, including bilateral primary sensorimotor and premotor cortices, the supplementary motor area, the basal ganglia and the cerebellum. No significant between-group differences were found for the simplest task (repetitive flexion-extension of one hand). However, the more complex tasks (alternate flexion-extension of both hands and fingers-to-thumb opposition movements) evoked significantly decreased activation in patients with PWS in dorsal premotor cortices, the supplementary motor area, and the cerebellum. A significant negative correlation (i.e., poorer performance, lower brain activation) was found between scores in the tGUG test and brain activation during coordinate hand movements in bilateral sensorimotor cortices in the PWS group.

Comment

Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced motor cortical activation during motor coordination.