The hypothesis set out in our original application is that t-VNS given over time and following a protocol established for its use in epilepsy, will prevent the prolonged and debilitating temper outbursts and associated emotional dysregulation that characteristically affect people with PWS. We further propose that any improvements in behavior are mediated through a normalization of the autonomic nervous system, which moderates response to threat.
The study is ongoing at present, with seven individuals with PWS, currently taking part. Each individual completes a baseline phase of 4-6 months, during which they get used to wearing the t-VNS but it is not switched on, while daily diaries about their usual behavior are completed. Baseline measures of autonomic nervous system function, such as heart rate variability, vocal prosody, and cortisol are also recorded, alongside the completion of cognitive tasks. Once baseline data is collected, participants enter the active phase, again lasting 4-6 months, where the same measures are undertaken, allowing comparisons of behavior and potential underlying mechanisms in the active and baseline phases to assess whether t-VNS has a positive effect, and, if it does, how this may work. At present two of the seven participants have recently entered the active phase. If an effect of t-VNS on behavior is found, we will initiate a third phase, in which the daily duration of stimulation will be reduced and then stopped to see if behaviors return as we anticipate.
These behaviors have limiting effects on the lives of those with PWS and place additional strain on those who support them. A treatment which improved these behaviors would be life-enhancing for those with PWS.
Mechanistic insights into the genetics of affective psychosis from Prader-Willi syndrome. Aman LCS, Manning KE, Whittington JE, Holland AJ. Lancet Psychiatry. 2018 Apr;5(4):370-378.
Tony Holland, MD
The University of Cambridge, United Kingdrom