Altered Gesture Imitation and Brain Anatomy in Adult Prader–Willi Syndrome Patients

Abstract

Objective: To explore motor praxis in adults with Prader–Willi syndrome (PWS) in comparison with a control group of people with intellectual disability (ID) and to examine the relationship with brain structural measurements. Method: Thirty adult participants with PWS and 132 with ID of nongenetic etiology (matched by age, sex, and ID level) were assessed using a comprehensive evaluation of the praxis function, which included pantomime of tool use, imitation of meaningful and meaningless gestures, motor sequencing, and constructional praxis. Results: Results support specific praxis difficulties in PWS, with worse performance in the imitation of motor actions and better performance in constructional praxis than ID peers. Compared with both control groups, PWS showed increased gray matter volume in sensorimotor and subcortical regions. However, we found no obvious association between these alterations and praxis performance. Instead, praxis scores correlated with regional volume measures in distributed apparently normal brain areas. Conclusions: Our findings are consistent in showing significant impairment in gesture imitation abilities in PWS and, otherwise, further indicate that the visuospatial praxis domain is relatively preserved. Praxis disability in PWS was not associated with a specific, focal alteration of brain anatomy. Altered imitation gestures could, therefore, be a consequence of widespread brain dysfunction. However, the specific contribution of key brain structures (e.g., areas containing mirror neurons) should be more finely tested in future research.

Cerebellar Dysfunction in Adults with Prader Willi Syndrome

“…Neuroanatomical and imaging studies have described cerebellar abnormalities [ 19 , 50 , 51 ] and reduced cerebellar volume in both children and adults with PWS compared with control samples [ 17 , 20 , 52 ]. Using voxel-based morphometry, findings from our group [ 8 ] and others [ 53 ] have revealed decreased relative white matter volume in the cerebellum. It is possible that our finding of abnormal cerebellar activation in PWS participants results directly from tissue volume reduction in this region.…”

“…Nevertheless, motor development is usually delayed and other motor symptoms appear later on [ 6 , 7 ], revealing an evolutive transformation of the motor control problems as the child grows up. At older ages, the PWS phenotype include a range of dyspraxia symptoms with deficient motor coordination (e.g., manual dexterity, graphomotor skills) and articulatory difficulties [ 3 , 6 , 8 , 9 , 10 ], severe postural instability, balance deficits, and gait disturbances [ 11 , 12 , 13 ], with a detectable decrease in muscle strength or weakness [ 10 , 14 , 15 , 16 ].…”

“…Current imaging studies have identified anatomical alterations in both the cerebellum and the sensorimotor cortex e.g., [ 8 , 17 , 18 , 19 , 20 ]. Functional alterations have also been reported implicating elements of the motor systems in terms of metabolism, functional connectivity at rest and abnormal activation in response to challenging stimuli related to eating behavior [ 5 , 21 , 22 , 23 , 24 , 25 ].…”

One Year of Recombinant Human Growth Hormone Treatment in Adults with Prader–Willi Syndrome Improves Body Composition, Motor Skills and Brain Functional Activity in the Cerebellum

“…On the other hand, the functioning of the motor cortex seems to be impaired in adult patients with PWS, who show hypo-excitability of these areas [ 15 ] and weaker activation in the cerebellum during motor coordination compared with controls [ 16 ]. Moreover, widespread structural and volumetric abnormalities in the brain may also affect some specific motor aspects [ 17 ].…”

Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader–Willi Syndrome

“…Prader–Willi Syndrome (PWS) is a rare genetic disease characterized by a series of disorders of hypothalamic functionalism: hyperphagia, obesity, hypogonadotropic hypogonadism, short stature due to GH deficiency [ 7 , 8 , 9 ], and cognitive, praxis, and behavioral disorders [ 10 , 11 , 12 ]. Up to 60% of adults with PWS have GH deficiency [ 13 ], which results in decreased muscle mass and strength and increased fat mass [ 14 ].…”