Noninvasive Neuromodulation of a Novel Cerebellar Satiety Circuit in PWS

Funding Summary

Our recent research identified a new brain pathway, the cerebellum-ventral striatum circuit, in regulating appetite and satiation. In the proposed study, we plan to test whether safe, non-invasive modulation of this circuit, using a technique called transcranial magnetic stimulation (TMS), can impact the function of this circuit and reduce food intake. 

Dr. Theresa Strong, Director of Research Programs, explains the details of the project in this video clip.

Lay Abstract

Overeating and hyperphagia are behavioral characteristics of PWS which are challenging for individuals with PWS and their families to manage. Considerable research and clinical efforts have been made to discover methods to reduce hyperphagia in PWS, including studies guided by the understanding that maladaptive behaviors stem from dysfunction in pathways in the brain that are responsible for appetite and food intake. These studies have included investigations testing the potential to modulate food intake behavior by targeting “traditional” brain pathways associated with appetite (including the hypothalamus and prefrontal regions). However, to date, these efforts have not translated to effective treatments. Our recent research used a combined translational approach which examined these pathways in animal models and in individuals with PWS and identified a new brain pathway, the cerebellum-ventral striatum circuit, in regulating appetite and satiation. In the proposed study, we plan to test whether safe, non-invasive modulation of this circuit, using a technique called transcranial magnetic stimulation (TMS), can impact the function of this circuit and reduce food intake. To do this, we will recruit a group of 12 individuals with PWS to complete 5 study visits involving safe, non-invasive brain imaging, TMS, and behavioral tests. We will examine our outcomes (feasibility and tolerability of cerebellar TMS, brain activation in the cerebellar-ventral striatum circuit, and food-related/hyperphagic behavior) in individuals undergoing active cerebellar TMS. This research is important because we currently do not have data on whether cerebellar TMS is feasible and tolerable in individuals with PWS, or whether manipulation of this novel brain pathway can reduce food responsivity and hyperphagia. In this study, we will be able to directly test these hypotheses for the first time in PWS. If we are successful, the next step would be to test this technique of cerebellar TMS in a larger group of individuals with PWS and to incorporate additional levels of treatment duration, variable TMS parameters, etc., to identify the optimal course of treatment. Through direct testing of the feasibility and initial efficacy of a short course of cerebellar TMS, this small pilot study will lay the foundation for the development of future clinical trials on cerebellar TMS for hyperphagia in PWS, towards a goal of lessening this challenging behavior for individuals with PWS and their families.