Publication Type Academic Article
Authors Ko J, Feigin A, Mattis P, Tang C, Ma Y, Dhawan V, During M, Kaplitt M, Eidelberg D
Journal J Clin Invest
Volume 124
Issue 8
Pagination 3656-66
Date Published 07/18/2014
ISSN 1558-8238
Keywords Brain, Parkinson Disease, Placebo Effect
Abstract Patient responses to placebo and sham effects are a major obstacle to the development of therapies for brain disorders, including Parkinson's disease (PD). Here, we used functional brain imaging and network analysis to study the circuitry underlying placebo effects in PD subjects randomized to sham surgery as part of a double-blind gene therapy trial. Metabolic imaging was performed prior to randomization, then again at 6 and 12 months after sham surgery. In this cohort, the sham response was associated with the expression of a distinct cerebello-limbic circuit. The expression of this network increased consistently in patients blinded to treatment and correlated with independent clinical ratings. Once patients were unblinded, network expression declined toward baseline levels. Analogous network alterations were not seen with open-label levodopa treatment or during disease progression. Furthermore, sham outcomes in blinded patients correlated with baseline network expression, suggesting the potential use of this quantitative measure to identify "sham-susceptible" subjects before randomization. Indeed, Monte Carlo simulations revealed that a priori exclusion of such individuals substantially lowers the number of randomized participants needed to demonstrate treatment efficacy. Individualized subject selection based on a predetermined network criterion may therefore limit the need for sham interventions in future clinical trials.
DOI 10.1172/JCI75073
PubMed ID 25036712
PubMed Central ID PMC4109544
Back to Top