Mapping alterations in the local synchrony of the cerebral cortex in Prader Willi syndrome

Abstract

Individuals with Prader Willi syndrome (PWS) often exhibit behavioral difficulties characterized by deficient impulse regulation and obsessive-compulsive features resembling those observed in obsessive-compulsive disorder. The genetic configuration of PWS aligns with molecular and neurophysiological findings suggesting dysfunction in the inhibitory gamma-aminobutyric acid (GABA) interneuron system may contribute to its clinical manifestation. In the cerebral cortex, this dysfunction is expressed as desynchronization of local neural activity. We used functional connectivity MRI to examine potential alterations in the local synchrony of the cerebral cortex in PWS. Whole-brain functional connectivity maps were generated using iso-distance average correlation (IDAC) measures in 22 patients with PWS and 22 control participants. Patients with PWS showed reduced local connectivity (weaker synchrony) in frontal areas, including the orbitofrontal cortex, ventral medial and lateral frontal regions, the anterior cingulate cortex, and sensory areas. The presence of obsessive-compulsive symptoms was significantly associated with the degree of functional structure alteration in part of the orbitofrontal and sensory cortices. In addition, abnormally heightened functional connectivity (stronger synchrony) was identified in the posterior cingulate cortex and the bilateral angular gyri, core components of the default mode network, with distance-dependent effects. Our findings of cortical synchrony alterations indicate a degree of overlap with the anatomy of the alterations previously observed in primary obsessive-compulsive disorder, while also suggesting the implication of GABAergic dysfunction in the pathophysiology of the disorder. Our observations may support the rational development of more specific therapeutic strategies in the treatment of behavioral disinhibition characteristic of PWS.