Signal to signature: transcranial magnetic stimulation as a biomarker of drug-induced cortical modulation in early-phase development

Abstract

This research focuses on the use of transcranial magnetic stimulation (TMS) as a biomarker to measure the effects of drugs on the brain at an early stage. An important objective in the development of new treatments for neurological and psychiatric disorders is to determine whether a drug truly affects the balance between excitatory and inhibitory processes in the brain. Reliable methods for measuring such effects are therefore needed.

This thesis investigated whether TMS can detect changes in brain activity following the administration of both established and experimental drugs. By combining measurements of brain activity (EEG) and muscle responses (EMG), insights were obtained into cortical excitability. The results demonstrate that TMS can capture subtle but consistent drug-induced effects. Effects of anti-epileptic drugs, antidepressants, and novel investigational compounds were detected, and TMS proved capable of distinguishing between different mechanisms of action.

Furthermore, the studies showed that findings in healthy volunteers largely correspond with results observed in patients with epilepsy, supporting the translation of early-phase research findings into clinical practice. Although further standardization and methodological refinement are required, the findings suggest that TMS has the potential to become a valuable tool in early drug development and could contribute to the more efficient development of new treatments for disorders of the central nervous system.