Parkinson's disease: Individual placebo responses are predicted by baseline expression of a striato-limbic network

Parkinson's disease (PD) is associated with substantial placebo effects. We used network analysis to identify a specific sham surgery-related pattern (SSRP) in metabolic PET data from a double-blind PD gene therapy trial. Baseline SSRP expression measured before randomization correlated with motor improvement under the blind after sham surgery. To validate this predictive relationship, we measured baseline SSRP levels in two independent placebo-controlled trials of pharmacologic PD treatments administered orally or by subcutaneous injection. As with sham surgery, pre-randomization SSRP expression correlated with placebo responses in each of the validation groups. Using magnetic resonance diffusion tensor imaging (DTI), we found that individual differences in SSRP expression and placebo response were attributable to variation in the density of fiber tracts linking key network nodes, particularly the nucleus accumbens and the anterior cingulate cortex. The findings support SSRP as a network-based imaging marker of placebo susceptibility in PD clinical trials.