Cortical morphology predicts placebo response in multiple sclerosis.

Area of Science:

• Neuroscience
• Clinical Trials
• Multiple Sclerosis Research

Background:

• Understanding long-term placebo responses, particularly in chronic diseases like multiple sclerosis (MS), remains limited.
• Previous research focused on acute placebo effects, with less known about sustained responses in clinical trial settings and their interaction with neurological disease.

Purpose of the Study:

• To investigate the brain correlates of sustained placebo responses in patients with multiple sclerosis (MS).
• To explore how brain structure and lesion load influence placebo effects in the context of a disproved MS treatment trial.

Main Methods:

• A randomized trial comparing balloon extracranial venoplasty to sham procedures in MS patients over 48 weeks.
• Analysis included MRI T2 lesion load, brain volumes, cortical thickness (CT), and graph theoretical analysis of CT covariance.
• Comparison of brain metrics between placebo responders and non-responders.

Main Results:

• A subset of patients in both treatment groups reported transient improvements, indicating placebo responses.
• Placebo responders and non-responders did not differ in overall lesion load or brain volumes.
• Responders exhibited higher lesion activity, while non-responders displayed a more small-world-like cortical thickness (CT) architecture, with lesion load inversely associated with CT in specific brain regions.

Conclusions:

• The neuropathological process in MS may alter cortical configuration, potentially limiting sustained placebo responses in some individuals.
• Brain structural differences, particularly in cortical architecture and lesion activity, are associated with the capacity for sustained placebo responses in MS.
• These findings highlight the complex interplay between brain structure, disease pathology, and placebo effects in chronic neurological conditions.